About Colorectal Cancer Treatment Methods

Articles about which Colorectal Cancer Treatment Methods are working well etc.


Survival Of Patients With Stage II Colorectal Cancer Improves With Intensive Postoperation Surveillance

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03 Feb 2006

Systematic postoperative surveillance of patients with rectal and colorectal cancer has demonstrated to produce an improvement in the survival of these patients. Nevertheless, it is currently discussed whether a more intensive surveillance strategy would provide significant advantage compared to a less aggressive strategy.

The methodology currently used for testing and the frequency tests are applied are highly heterogeneous. So, in order to compare the efficiency of two surveillance strategies, a standard strategy and an intensive strategy, physicians of Hospital Cl?nic conducted a prospective, multicentre and randomised study in patients affected by this type of cancer.

This trial, supported by the Medical Technology Agency of the Catalan Government, was led by Dr. Francisco Rodr?guez-Moranta and Dr. Antoni Castells, from the IDIBAPS Physiopathology of the Gastrointestinal Lesions Group, and had the collaboration of specialists of Hospital de Terrassa and Hospital General de Vic. The results of these comparison were published in Journal of Clinical Oncology (24(3):386-93), and showed that the most intensive therapy benefited patients in certain stages of cancer and patients with rectal lesions, whose overall survival was increased.

To conduct this study, 259 patients from the three centres with colorectal cancer in stage II or III (which are intermediate states in a scale ranging I-IV) were recruited and were randomly distributed in two surveillance experimental groups. In the first group, 132 patients received the simplest standard surveillance, consisting in the clinical evaluation and in the monitoring of blood tumour markers every three months.

In the second group, the 127 patients were applied a strategy that, in addition to the standard, consisted in an abdominal CT-scan or ultrasonography, chest x-ray and colonoscopy. Both groups of patients were similar with respect to baseline characteristics as disease, tumour recurrence rate and type of tumour. After 48 months of follow-up, researchers did not detect significant difference in the overall survival between patients the of the two groups. However, as specific subgroups were analysed, the intensive strategy was associated to a higher survival, in number of years, in patients of stage II tumours and those with rectal lesions. Thus, this type of surveillance benefited this subtype of patients since relapse could be detected earlier. Particularly, colonoscopy was the method responsible for the detection of the highest proportion (44%) of recurrences of operable tumours.

According to the authors, this invasive strategy would improve the prognosis of patients with stage II colorectal cancer and also patients with rectal lesions. In this sense, they recommend the periodical colonoscopy during the first 5 years of postoperatory follow-up, a practice that is already applied in Hospital Cl?nic. The level of cost efficiency of this strategy is justified by the higher healing rate in case of relapse, since tumours are detected in their onset. Nevertheless, this strategy does not show more efficiency in other cases and it is important to continue to search for the most specific techniques for every case in order to avoid nonessential health expense. Although these results do not permit to define the perfect strategy for the follow-up of all patients with colorectal cancer, it permits to establish a strategy suitable for an important subgroup of patients (nearly half of patients suffering from this disease). The journal has written an editorial comment about the article in which both the study and the Catalan Government Support are acclaimed.
http://www.medilexicon.com/medicalnews.php?newsid=37048∞

Clinical Trial Buddy Program Among Innovative Support Offerings From The Colon Cancer Alliance

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28 Feb 2006

Colon Cancer patients considering participation in a clinical trial can now access a first-of-its-kind peer-to-peer support system, the Buddy Program, the Colon Cancer Alliance (CCA) announced today. As a result of this innovation, an experienced mentor will provide guidance to newly diagnosed patients about how to prepare for clinical trials and understand the process. The announcement comes as the CCA marks the seventh Annual National Colorectal Cancer Awareness Month in March.

Although more Americans have become aware of colon cancer in recent years, one person still dies of the disease every nine minutes. Research shows the mortality rate will likely decrease if patients and caregivers have a better understanding of how to treat the disease. In fact, thousands of clinical trials are available for patients to try new, experimental and investigational drugs. But fewer than five percent of adult cancer patients currently choose to participate in them.

"For the first time, colorectal cancer patients will have the opportunity to be educated about clinical trials by someone who has just been in their shoes," said Amy Kelly, Co-Founder and Executive Director of the CCA. "We expect that the intimacy of this experience will encourage more patients to join trials. As more people participate, we will develop the necessary research to find the best treatments for the disease."

Since 1995, participation in clinical trials has declined due to long-standing fear, apprehension and skepticism. Doctors also may not mention trials as an option and access problems still exist. To help maximize the CCA's Buddy Program and address some of these problems, all potential mentors will undergo training to ensure that they can offer the most appropriate guidance. The clinical trial component will expand an existing program in which colon cancer survivors, their families and friends are able to speak to others who have "been there." These buddies provide a personal perspective on coping with side effects, treatment options, life after a colostomy and many other emotional issues. Those interested in learning more about the buddy program can visit www.ccalliance.org∞.

The CCA also has implemented additional educational initiatives as a result of feedback from patients and caregivers. This year the nonprofit plans to add live operators to its help-line, develop patient education materials in Spanish, distribute more free materials to doctors and hospitals, add more guest speakers to on-line chats, continue to grow its local chapter program, Voices, and expand colon cancer conference sites and locations throughout the United States. The Alliance also will make press kits available via their Web site for local groups or individuals wishing to promote National Colorectal Awareness Month.
http://www.medilexicon.com/medicalnews.php?newsid=38456∞

Investigation Into Improving Quality Of Life After Cancer

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28 Jun 2006

Researchers at the University of Liverpool have been awarded ?1.9 million to further understanding of how the quality of patients' lives can be improved following serious illness.

The ?Cancer Experiences Collaborative' will investigate ways in which patients and their families can cope more effectively and maximise the benefits of treatment. Researchers also aim to improve the understanding of the social, psychological and clinical problems experienced by elderly people and people with cancer.

Professor Mari Lloyd-Williams leads Liverpool's Academic Palliative and Supportive Care Studies Group, said: ?The experiences of people affected by cancer can help further understanding of the disease so that improvements in facilities, clinical environments and supportive care can be specifically targeted.

?As well as carrying out new programmes of research, we will be supporting and mentoring individuals to enable them to become independent researchers in palliative and supportive care.?

The University of Liverpool is already an international centre of excellence for palliative and supportive care research. Academics will focus on how to manage specific symptoms such as depression, nausea, fatigue and breathlessness associated with cancer and other end-stage illnesses in order to allow the greatest quality of life.

Together with the Universities of Lancaster, Manchester, Sheffield and Southampton the University of Liverpool will also be working with leading hospice charities, cancer clinicians and service providers. The research, funded by the National Cancer Research Institute, also aims to improve clinical practice and the way palliative and supportive care services are organized
http://www.medilexicon.com/medicalnews.php?newsid=46065∞

Factors Associated With Incomplete Chemotherapy For Colon Cancer Identified By New Study

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06 May 2006

Physical frailty, treatment complications, and lack of social and psychological support may explain why elderly stage III colon cancer patients do not complete a course of chemotherapy after surgery, according to a study in the May Journal of the National Cancer Institute.

Several trials in the late 1980s led a 1990 National Institutes of Health Consensus Panel to recommend adjuvant chemotherapy, or chemotherapy given after surgical removal of a tumor, for stage III colon cancer patients. However, despite recommendations, many patients do not initiate or complete adjuvant chemotherapy.

Sharon Dobie, M.D., of the University of Washington in Seattle, and colleagues analyzed data from 3,193 stage III colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) registries, who began adjuvant chemotherapy treatments. Patients, identified through Medicare claims, were assessed by whether they completed their chemotherapy treatment, as well as by their sociodemographic, clinical, and environmental characteristics and their physicians' characteristics.

The authors found that of the 3,193 patients who chose to initiate chemotherapy, 2,497 (78.2%) of patients completed a course of adjuvant chemotherapy. Patients who completed adjuvant chemotherapy had a reduced risk of death. An incomplete course of chemotherapeutic treatment was associated with factors related to physical frailty, treatment complications, and a lack of social and psychological support. Their physicians' characteristics did not affect whether they completed chemotherapy. African-Americans were equally likely to finish treatment as Caucasians.

The authors write, "From these findings, interventions to improve social and physical support throughout the treatment course could be implemented to test whether such support improves rates of chemotherapy completion in elderly colon cancer patients."

In an accompanying editorial, Victor R. Grann, M.D., from Columbia University's College of Physicians and Surgeons, and Franco M. Muggia, M.D., from New York University School of Medicine, suggest the paper's results verify the importance of completion of adjuvant chemotherapy for optimal survival. They write, "The findings are worthy of comment and should add to the education of medical oncologists and other physicians who participate in the management of patients undergoing curative resections for colon cancer."
http://www.medilexicon.com/medicalnews.php?newsid=42702∞

Colon Cancer Survivors: Moderate Exercise Improves Survival Rates

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16 Jul 2006

People who have been treated for colon cancer can substantially reduce the risk that the disease will return and improve their overall chance of survival by engaging in regular exercise, according to new research by Dana-Farber Cancer Institute scientists.

In a pair of studies published on the Journal of Clinical Oncology website http://www.jco.org/early_release/∞, and slated to appear in the journal's Aug. 1 issue, the researchers found that colon cancer patients engaging in moderate levels of exercise six to 12 months after completing therapy had an approximately 50 percent higher survival rate than those who didn't exercise. The improvement took place in patients with very early and more advanced (but non-spreading) colon cancer, all of whom had undergone surgery intended to cure the disease.

"From previous studies we know that regular physical activity reduces the risk of developing colon cancer, but until now few studies have looked at the survival effect of exercise on people who have been treated for disease," says the study's lead author, Jeffrey Meyerhardt, MD, MPH, of Dana-Farber. "While our work found a significant benefit for patients who exercise, it's important that exercise be seen as a supplement to, not a replacement for, standard therapies."

The two studies used different sets of data to arrive at their shared conclusion. One study involved 832 patients with stage III colon cancer (involving the lymph nodes around the tumor but with no signs of having spread outside the area) who had received surgery and follow-up chemotherapy as part of the Cancer and Leukemia Group B (CALGB) national clinical trial. Data on participants' recreational physical activities and health status was collected about six months after the completion of therapy.

Researchers found that patients who engaged in moderate physical activity - the equivalent of walking six or more hours a week at an average pace of 2-2.9 miles per hour - were 47 percent more likely to be alive and free of disease than those who were less physically active.

The other study involved 573 participants in the Nurses' Health Study, a project organized by Brigham and Women's Hospital which tracks the health of 121,700 female registered nurses by questionnaires mailed every two years. The nurses included in the current study had undergone surgery intended to cure stage I to III cancer at least six months earlier.

The results of this study mirrored those of the CALGB-based study. Additionally, patients who increased their physical activity from levels before diagnosis had an approximately 50 percent lower chance of dying, from colon cancer or any other cause, than those who remained physically inactive.

"The fact that two different sets of data have yielded such similar results encourages us about the validity of our findings," Meyerhardt remarks. "Although the data from the CALGB study did not include data on the participants' exercise levels prior to diagnosis with colon cancer, we do have that information for those in the nurses study. From that data, it appears that the amount of exercise prior to diagnosis doesn't affect the outcome of treatment. What matters is exercising after standard therapy has been completed."

Scientists do not have a definite physiological explanation for the benefit of exercise for colon cancer survivors, but they speculate it may be tied to a reduction in the body's production of insulin and a similar compound, insulin-like growth factor, which fuel the growth of some cancer cells.

"To reduce the chances that colon cancer will return after treatment, as well as for overall health reasons, regular exercise is a good option for survivors to consider," says Meyerhardt, who also is an assistant professor of medicine at Harvard Medical School. "As with any exercise program, people should check with their doctor before increasing their degree of physical activity."
http://www.medilexicon.com/medicalnews.php?newsid=47297∞

Roche Bowel Cancer Drugs Meet Phase III Endpoints

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02 Aug 2006

Swiss pharmaceutical group Roche said on Monday its cancer drugs Avastin and Xeloda had met primary endpoints in a late-stage study for metastatic colorectal cancer.

The study shows that by combining Xeloda and Xelox was as effective as rival drug Folfox when tested on 2,035 previously untreated patients.

And Avastin, a medicine that inhibits the growth of blood vessels that nourish cancer cells, in the phase III study improved the time that patients lived without the disease progressing when added to chemotherapy of either kind.

"This is the first time that we have significant data showing that oral Xeloda in combination with oxaliplatin is as effective as Folfox, demonstrating that Xelox provides a new treatment option for colorectal cancer patients," Ed Holdener, head of global development at Roche, said.

Xeloda, oxaliplatin and Avastin are already being marketed individually by Roche in several countries.

The results from the study will be submitted to a future international cancer congress, the company said, with an eye on ultimately marketing them for the new indications.
http://www.medilexicon.com/medicalnews.php?newsid=48520∞

New Model Measures Drug's Ability To Penetrate Colon Tumor Cell Layers

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17 Aug 2006

Scientists have developed a model of a tumor's vascular system to determine how cancer drugs distribute in tumors. The ability of drugs to penetrate tumors is one factor that determines their actual anticancer activity. Kevin O. Hicks, Ph.D., of the University of Auckland in New Zealand, and colleagues measured the ability of tirapazamine, a drug activated in oxygen deficient cells, to penetrate cell layers of a type of colon cancer. With this information, they were able to create a three-dimensional model of drug distribution in a tumor. They then compared the predictions of cell death from this model with actual results in mouse tumors. Their model accurately predicted the ability of tirapazamine and closely related drugs to penetrate the colon tumor and kill tumor cells.

In an accompanying editorial, Edward A. Sausville, M.D., Ph.D., of the University of Maryland in Baltimore, discusses the implications of Hicks et al.'s approach on the development of small-molecule anti-cancer compounds. He writes, "Unless the diffusion and drug transport properties of an agent are optimized, what looks good in tissue culture experiments will likely look less promising when applied to the human milieu."
http://www.medicalnewstoday.com/medicalnews.php?newsid=49768&nfid=30587∞

ASCO, NCCN Release Seven Quality Guidelines For Breast, Colorectal Cancer Care

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22 Aug 2006

The American Society of Clinical Oncology and the National Comprehensive Cancer Network on Tuesday released seven quality guidelines∞ for breast and colorectal cancer care, CQ Today reports. The guidelines are based on clinical impact, feasibility, potential for improvement, reliability, scientific acceptability and usefulness. They include post-operative chemotherapy recommendations for people ages 80 and younger; hormonal therapy recommendations for people with tumors one centimeter or larger; and breast radiation therapy recommendations for women ages 70 or younger (CQ Today, 8/17). According to the guidelines, the recommendations -- three breast cancer-related, two rectal cancer-related, one colon cancer-related and one colorectal cancer-related -- continually will be tested by the organizations and will be updated to reflect the findings of such tests (ASCO/NCCN, "ASCO/NCCN Quality Measures: Breast and Colorectal Cancers," 8/15).
http://www.medilexicon.com/medicalnews.php?newsid=50040∞

NICE Issues Updated Guidance On Keyhole Surgery For The Treatment Of Colorectal Cancer

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23 Aug 2006

New guidance published today by the National Institute for Health and Clinical Excellence (NICE) recommends laparoscopic (?keyhole?) surgery as an option for patients with colorectal cancer. The guidance, which replaces previous NICE guidance published in 2000, applies to patients in whom both laparoscopic and conventional open surgery would be considered as suitable options for treatment.

Colorectal cancer is the third most common cancer in the UK. Almost 30,000 new cases were registered in England and Wales in 2002, representing over 12% of all new cancer cases. In 70% to 80% of patients, complete excision of the tumour may be able to cure the condition. At present, the standard procedure for surgical resection of colorectal tumours uses the open approach to remove the tumour and the affected part of the large intestine via an abdominal incision.

Laparoscopic colorectal surgery involves inserting laparoscopic instruments through a number of holes in the abdominal wall to dissect tissues around the tumour. The tumour is then usually removed through an abdominal incision. The NICE guidance also applies to laparoscopically assisted surgery, in which the incision is enlarged to complete the dissection before the tumour is removed.

Professor David Barnett, Chair of the independent Appraisal Committee that produced the guidance, said: ?When NICE produced its original guidance in 2000 there was a lack of evidence about the long term outcomes of the laparoscopic approach compared to the conventional open technique. That has now changed and recent evidence indicates that the long term outcomes for patients are equivalent for both techniques. In addition there are important additional benefits associated with laparoscopic surgery, both in terms of shorter hospital stays and the ability of patients to return to normal activities post-operatively faster than with conventional surgery. This guidance makes it clear to the NHS and patients, no matter where they live in England and Wales, how and under what circumstances this procedure can add value so that those patients who can benefit from the procedure will now be able to do so.?

The NICE guidance on the use of laparoscopic surgery for colorectal cancer recommends that this should only be performed by surgeons who have completed appropriate training in the technique, and who perform this procedure often enough to maintain competence. The Appraisal Committee considered that appropriate training of surgeons and surgical teams is essential to ensure the clinical effectiveness and safety of the laparoscopic technique. Given the current shortage of surgeons skilled in this technique, NICE has today advised the Department of Health that they need to consider varying the usual three month period that the NHS is required to fund NICE technology appraisal guidance. The Department of Health are considering this request and will make an announcement as soon as possible.

Ends Further information: Phil Ranson - 020 7067 5903 or 07786 390068 Notes for editors About NICE

1. NICE is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.

2.NICE produces guidance in three areas of health:

_-- public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector

_-- health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS

_-- clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

http://www.nice.org.uk∞
http://www.medilexicon.com/medicalnews.php?newsid=50236∞

Vioxx Reduces The Risk Of Colorectal Polyps, Study Finds

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01 Sep 2006

A researcher from Dartmouth reports the results of a clinical trial that shows that the cyclooxygenase-2 (COX-2) inhibitor rofecoxib (VIOXX?) reduces the risk of colorectal adenomas, or polyps. Polyps are benign tumors that are precursors to colon cancer, and they are often found in older adults.

The results of the study appeared online on August 30 at the American Gastroenterological Association website [http://www.gastro.org/∞] in advance of being published in the journal, Gastroenterology. Extensive data have suggested previously that aspirin and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce colon cancer risk, and this study now demonstrates a similar effect for VIOXX®. The study is at: http://www.gastro.org/user-assets/Documents/13_Media/Randomized_Trial.pdf∞

"These are exciting findings," says Dr. John Baron, the lead author of the paper and a professor at Dartmouth Medical School, who has been studying chemoprevention of colorectal cancer for more than twenty years. "They show once again the potential for NSAIDs to interfere with the development of cancer in the colon and rectum."

This study, called the APPROVe (Adenomatous Polyp Prevention on VIOXX?) study, was a randomized, placebo-controlled, double-blind trial conducted by Merck Research Laboratories. The study involved 108 sites in the United States and abroad and followed 2,587 patients with a recent history of confirmed colorectal adenomas. After removal of all polyps, the subjects were randomized to receive daily placebo or 25 mg rofecoxib on a daily basis. The primary endpoint was to analyze all adenomas diagnosed during the three-year treatment period based upon colonoscopies conducted one year and three years after baseline.

In addition, an extension to the APPROVe study was conducted to assess recurrence of adenomas in the year following the end of the three years' treatment through a colonoscopy at year four. Previous randomized studies have also shown that COX-2 inhibitors can lower the risk of polyps in patients with a rare genetic syndrome called familial adenomatous polyposis (FAP), but this is the first to illustrate the effect in the broad population of people at risk for colorectal cancer.

Patients taking rofecoxib had a lower recurrence rate of adenomas than those taking placebo (41 percent vs 55 percent; p<0.0001; relative risk 0.76; 95 percent CI 0.69-0.83). Rofecoxib also reduced the risk of advanced adenomas, which are polyps that are more likely to become cancerous. The chemopreventive effect was larger in the first year (RR 0.65; 95 percent CI 0.57-0.73) than in the subsequent two years (RR = 0.81, 95 percent CI 0.71-0.93). In the year following three years' treatment, patients taking rofecoxib experienced a slightly increased risk of any adenoma, but not of advanced adenomas. However, over the entire length of the trial (three years of treatment and one year off drug), patients taking rofecoxib experienced a reduction of the risk of any adenoma.

Baron says that patients treated with rofecoxib experienced more serious adverse events, including significant upper gastrointestinal events and, as reported previously, increased risks of thrombotic cardiovascular events. But he does not believe that the side effects will derail the eventual development of effective chemoprevention.

"While the toxicity of the currently available COX-2 inhibitors may be problematic, the demonstration of efficacy certainly implies that other agents may be suitable for longer term use," he says.
v Baron says that although it is not known how rofecoxib interferes with carcinogenesis, inhibition of COX-2 has been thought to play a role. Other mechanisms are possible, however, and scientists are actively seeking to understand exactly how non-steroidal anti-inflammatory drugs after pathways that lead to cancer.
http://www.medilexicon.com/medicalnews.php?newsid=50841∞

Unlocking Colon Cancer With Key Of Prevention

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01 Sep 2006

An international team of scientists reports that a single 400-milligram daily dose of celecoxib, commonly called Celebrex? and manufactured by Pfizer, significantly reduced recurrence of adenomas, or pre-malignant colon tumors - within three years of previous adenoma removal.

The New England Journal of Medicine today published findings from the Prevention of Spontaneous Adenomatous Polyps (PreSAP) study, involving more than 1,550 participants at 107 sites in 32 countries on six continents. The study was led by Nadir Arber, M.D., chair of the Integrated Cancer Prevention Center and professor of medicine and gastroenterology at the Tel Aviv Sourasky Medical Center and Bernard Levin, M.D., vice president of Cancer Prevention and Population Sciences at The University of Texas M. D. Anderson Cancer Center.

"Celecoxib 400 mg once daily significantly reduced colorectal adenoma occurrence, with a greater effect on advanced adenomas," said Arber.

As excess amounts of the protein cyclooxygenase (COX-2) are associated with adenomas and colon cancer, PreSAP researchers studied celecoxib - a selective COX-2 inhibitor - to prevent the pre-cancerous lesions.

"There is no doubt that celecoxib is an effective agent in reducing the size and occurrence of adenomas in patients with higher risks for colorectal cancer," said Levin.

In the placebo-controlled, double-blind PreSAP trial, study leaders randomly assigned participants to receive either a single 400-mg dose of celecoxib (approximately 930 subjects) or a placebo (nearly 630 subjects). Subjects received colonoscopies after one and three years to detect potential pre-malignant tumors and their sizes, as well the overall adenoma burdens for participants. All polyps were removed and examined by study pathologists.

At the conclusion of the trial, the cumulative adenoma rate for the celecoxib study group was 33.6 percent, while the cumulative rate of adenoma development in the placebo group was 49.3 percent (a 36 percent reduction). Celecoxib administration was associated with a 50 percent reduction in larger, potentially more dangerous adenomas.

"Unlike the recent Adenoma Prevention with Celecoxib (APC) trial, we did not find a statistically significant increase in cardiovascular risk associated with the use of 400 mg of celecoxib once daily," said Levin. "That said, because of the significant cardiac side effects seen in the APC study, further cardiovascular research on the use of all anti-inflammatory drugs, such as Celebrex?, Aleve? and Motrin?, as chemoprevention tools is warranted.

"Low dose aspirin also has been shown to reduce adenoma formation in individuals with a prior history of polyps and has the potential to decrease cardiovascular disease risk," said Levin. "However, its use is associated with an increased risk of upper-gastrointestinal bleeding and stroke."

The three-year APC study, with more than 2,000 participants, sought to reduce adenoma size and occurrence through the use of celecoxib. In the study, APC researchers administered celecoxib twice daily at either 200 mg or 400 mg doses. The study showed that the drug nearly doubled cardiovascular risk to participants.

"While our findings are exciting in that they suggest great potential for reducing adenoma formation in patients with high risk for colorectal cancer, we've scratched the surface with the PreSAP trial," said Levin. "Until these impressive prevention results are realized with lessened cardiovascular risk, we cannot advise celecoxib routinely as a tool for colon cancer prevention. Once daily dosing may provide an important insight into ways to diminish the untoward cardiovascular effects of celecoxib."
http://www.medilexicon.com/medicalnews.php?newsid=50889∞

Growth Of Colorectal Tumors In Mice Checked By Grape Seed Extract And Cell Cycle Halted

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http://ostomyland.com/wiki/AntioxidantInfo∞
(third article)

First Human Use Study Of Third Eye Retroscope(TM) Underway - Suggests That New Device May Improve Detection Of Colon Cancer

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11 Oct 2006

Today Avantis Medical Systems, Inc. announced commencement of the first clinical study of the Third Eye Retroscope(TM), a new device for colorectal cancer screening and surveillance.

Used during colonoscopy, the Third Eye Retroscope is an auxiliary imaging device that provides an additional view to reveal polyps, cancers and other lesions that might be hidden from the lens of the traditional forward-viewing colonoscope.

Developed by Avantis Medical Systems, Inc. of Sunnyvale, Calif., this innovative device is passed through the instrument channel of a standard colonoscope until it extends beyond its tip. As it emerges, the device automatically turns around 180 degrees to aim "backward" toward the tip of the colonoscope. Then, as the colonoscope is withdrawn from the colon, the Third Eye comes along with it, providing a continuous retrograde view to complement the forward view of the colonoscope.

Colonoscopy is widely regarded as the "gold standard" for detection of abnormalities in the colon. However, previous research has revealed that 12-24% of polyps and a significant number of cancers can be missed during colonoscopy, especially if they lie behind folds in the colon wall (1,2,3). This new device is designed to solve that problem by allowing the physician to view the opposite side of those folds during the procedure.

An earlier laboratory bench study(4) found that use of the device resulted in a dramatic improvement in the ability of endoscopists to detect simulated polyps in anatomical models.

Of the polyps located on the proximal aspect of haustral folds in the models -- i.e., the opposite side when viewed from below -- the endoscopists detected only 12% with a standard colonoscope. However, they found 81% of the polyps when using a prototype of the Third Eye Retroscope in conjunction with an identical colonoscope. That study attracted a great deal of interest when it was presented at a plenary session of Digestive Disease Week (DDW) 2006.

Now George Triadafilopoulos, M.D. has used the device in humans for the first time, and is very impressed with the results.

Dr. Triadafilopoulos is Clinical Professor of Medicine at Stanford University School of Medicine and Editor-in-Chief of the leading journal, Gastrointestinal Endoscopy. Working at El Camino Hospital in Mountain View, California, where he has his private practice, Dr. Triadafilopoulos used the device during routine screening colonoscopy.

According to Dr. Triadafilopoulos, "Despite its remarkably small size, the image provided by the Third Eye Retroscope device is adequate to allow visualization of areas that are difficult or impossible to view with a standard colonoscope, including the proximal aspects of haustral folds and the inner curves of flexures. In fact, today I saw areas that I've never been able to see before during colonoscopy."

Fred Seddiqui, President and CEO of Avantis, states, "This was a terrific beginning for our first clinical study. We are optimistic that the results will demonstrate that a small, disposable ancillary device can dramatically improve the ability of endoscopists to detect colorectal cancer in its earliest stages."

Mr. Seddiqui points out that the next step will be to perform a larger study to evaluate the device's efficacy. He says, "That will involve a direct comparison of detection rates with the Third Eye device vs. detection rates with the colonoscope alone.

Dr. Triadafilopoulos feels that a major advantage of the Third Eye Retroscope is that it fits through the working channel of virtually any adult colonoscope, so "... facilities won't face major outlay for capital equipment to replace the existing infrastructure. Also, because the device complements, rather than replaces, standard colonoscopy technique, it involves minimal training for endoscopists and avoids disruption of existing referral patterns."

The Third Eye Retroscope has not yet been submitted for domestic (FDA) or international regulatory clearance and thus is not available for sale.
http://www.medilexicon.com/medicalnews.php?newsid=53780∞

Guidelines For Advanced Colorectal Surgery Often Not Followed

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21 Oct 2006

The majority of patients with locally advanced colorectal cancer do not receive the extensive surgery to remove the cancer and adjacent tissues, a new study reports. This extensive surgery, called a multivisceral resection, is recommended by the National Cancer Institute and American Society of Colon and Rectal Surgeons because it reduces local recurrence and improves survival.

Calvin H.L. Law, M.D., F.R.C.S.C., of the University of Toronto, and colleagues identified 8,380 patients 18 years and older who received surgery for nonmetastatic, locally advanced colorectal cancer between 1988 and 2002. They used data from the Surveillance, Epidemiology, and End Results registry.

They found that only 33.3% of patients were treated with the recommended surgery. Patients given the recommended surgery had increased overall survival, compared to those given less extensive surgery.
http://www.medilexicon.com/medicalnews.php?newsid=54463∞

Aspirin Takers With A Genetic Variant May Have Lower Colorectal Adenoma Risk

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21 Oct 2006

A genetic variation (G315A) in the ODC gene may change a person's response to aspirin given for colorectal cancer prevention.

Elizabeth Barry, Ph.D., of the Dartmouth Medical School in Lebanon, N.H., and colleagues assessed the effect of the ODC genotype in 973 patients in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to receive either placebo or aspirin. They were followed for three years to see if they developed colorectal adenomas, a type of polyp. The G315A variation in the ODC gene was not associated with colorectal adenoma incidence overall. However, subjects with at least one variant gene had a lower risk of developing colorectal adenomas if they were taking aspirin while subjects without the gene mutation did not benefit from aspirin treatment.
http://www.medilexicon.com/medicalnews.php?newsid=54464∞

Effective Prevention Of Colorectal Cancer With Virtual Colonoscopy

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21 Oct 2006

Three-dimensional computed tomography (CT) colonography, also known as virtual colonoscopy, is an accurate screening method for colorectal cancer, according to a study published in the November issue of the journal Radiology. In addition, when covered by third-party payers, virtual colonoscopy may entice more people to be screened.

"Our positive experience with virtual colonoscopy screening covered by health insurance demonstrates its enormous potential for increasing compliance for colorectal cancer prevention and screening," said lead author Perry J. Pickhardt, M.D., associate professor of radiology at The University of Wisconsin Medical School in Madison. "In addition, recent technical improvements have resulted in even better performance results."

Colorectal cancer remains the second leading cause of cancer mortality in the United States, and the American Cancer Society (ACS) estimates that there will be 148,610 new cases diagnosed in 2006 and 55,170 deaths. The disease is largely preventable through screening for colon polyps, which are benign growths that may develop into cancer if not removed. ACS recommends that people at average risk for colorectal cancer begin regular colorectal cancer screening at age 50, but current compliance with this recommendation remains well below 50 percent. Many people resist screening because of the discomfort and inconvenience caused by the standard optical colonoscopy test.

"Our goal is not to take patients away from existing strategies like optical colonoscopy, but rather to attract those who are currently not being screened at all," Dr. Pickhardt said.

Virtual colonoscopy is less invasive than optical colonoscopy and produces precise and detailed 3-D "fly-through" images of the entire colon's interior without having to insert a scope. With virtual colonoscopy screening, there is essentially no risk of bleeding or of perforating the colon. There is no need for intravenous sedation, and the procedure is less costly than conventional colonoscopy. It also is more convenient, typically taking 10 minutes or less, because patients need not recover from sedation.

"Both virtual colonoscopy and optical colonoscopy are excellent screening tests," Dr. Pickhardt said. "The advantages of virtual colonoscopy over optical colonoscopy at our institution are that it is safer, faster, less costly, more convenient, involves an easier bowel prep, and yet is just as effective for detecting important polyps and cancers."

In April 2004, local third-party insurance coverage was initiated for virtual colonoscopy screening by the major managed care providers in the Madison area. Over a one-year period, the researchers performed virtual colonoscopy screening exams on 1,110 asymptomatic adults, consisting of 585 women and 525 men with a mean age of 58.1 years.

Large (10 millimeters [mm] or more) colorectal polyps were identified in 43 (3.9 percent) of patients. Medium-sized lesions (6 mm - 9 mm) were identified in 77 (6.9 percent) patients. Patients without polyps 6 mm or larger were advised to follow a routine screening interval of five years. Most patients with medium-sized lesions chose to undergo follow-up with virtual colonoscopy. If all the patients with either a polyp larger than 6 mm or a nondiagnostic segment had undergone subsequent optical colonoscopy, the maximum referral rate would have been 11.9 percent.

Seventy-one of the 1,110 patients (6.4 percent) underwent subsequent optical colonoscopy. Sixty-one of these procedures were performed on the same day as virtual colonoscopy to avoid the need for repeat bowel preparation. The optical colonoscopy findings were in agreement with the virtual colonoscopy findings in 65 of the 71 patients.

The high rate of accuracy coupled with the low necessity for subsequent optical colonoscopy show virtual colonoscopy to be an attractive screening tool for colorectal cancer.

"In our experience, providing a less invasive, yet equally effective screening option like virtual colonoscopy has drawn many adults off the sidelines," Dr. Pickhardt said. "Since colorectal cancer is uniquely preventable, widespread virtual colonoscopy screening could lead to a significant reduction in mortality from this deadly disease."

Dr. Pickhardt anticipates that the positive clinical results of this study will lead to further acceptance from the medical community and that insurance coverage on the national level should start to take place within the next one to two years.
http://www.medilexicon.com/medicalnews.php?newsid=54424∞


Medicsight Announces FDA Market Clearance For ColonCAR Software

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28 Nov 2006

Medicsight PLC (Amex: MGT) announced today it has received FDA 510(K) clearance for Medicsight ColonCAR 1.2.1, an image analysis software tool designed to be used with CT colonography (virtual colonoscopy) to assist radiologists in searching for and measuring potential colorectal polyps. Medicsight introduced the product at the 92nd Scientific Assembly and Annual Meeting of the Radiological Society of North America conference this week at McCormick Place in Chicago.

Medicsight's ColonCAR (Computer Assisted Reader) uses a series of filters deployed against image data from CT colonography studies. The filters highlight spherical areas as small as 5mm (or the size of a small pea), allowing radiologists to examine these areas in 3D in order to judge their potential as true polyps.

Radiologists are also able to manually highlight any irregularities for closer inspection. Once suspected polyps are found, the software can determine the shape and features, precisely identifying the boundaries and showing the lesion in 3D with automatic diameter and volume measurements. This allows the radiologist to accurately review and monitor polyps over time.

"We are really excited about bringing this innovative and leading product to market and the benefits it will mean for radiologists," says Etienne Vanderstokker, CEO of Medicsight PLC. "We are confident that the integrated solution will create ideal workflow and optimize reading times for end user productivity, thereby giving Medicsight the opportunity to capitalize on the ever increasing customer demand for CAD."

Medicsight PLC will be present during RSNA, which is being held from November 26th through December 1st, 2006 at Chicago's McCormick Place, and will show their product at the South Building A, booth (#5544).

Colorectal cancer is the third most common cancer found in men and women in the U.S., according to the National Cancer Institute. American Cancer Society statistics on colon and rectal cancer estimated 148,610 new colorectal cases to be diagnosed in 2006, accounting for almost 14 percent of annual cancer deaths.

The Medicsight ColonCAR software will be integrated within leading imaging 3D advanced visualization products from TeraRecon Inc., Viatronics Inc. and Vital Images Inc. Medicsight announced FDA 510(k) clearance for ColonCAR last Thursday, November 23rd.

Medicsight's ColonCAR software will also be available for order through a new medical portal, Medicexchange.com, which is being launched this week at the RSNA show in Chicago.
http://www.medilexicon.com/medicalnews.php?newsid=57562∞

What Cures Your Aches Might Prevent Cancer

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02 Dec 2006

Mayo Clinic Cancer Center has begun three clinical studies looking at the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent cancer -- colon, esophageal or lung. These studies are part of the ongoing Cancer Center chemoprevention program, using medications to prevent cancer, especially for people with increased cancer risk.

"While searching for the cure is important, even more so is finding effective ways to prevent cancer," says Paul Limburg, M.D., M.P.H., Mayo Clinic gastroenterologist and lead researcher on the colon cancer prevention study. "We have observed that some of the same biological processes that cause inflammation may also be involved in developing cancer, so the next step was to see if drugs that prevent inflammation also serve to lessen the risk of cancer."

The colon cancer study is looking at the NSAID sulindac (Clinoril), and its ability to inhibit inflammation and subsequent transformation of damaged cells into cancer cells. Sulindac's preventive effect will be measured against that of two other potential prevention agents: atorvastatin (Lipitor), a cholesterol-lowering drug with some reported cancer prevention aspects (Cancer Research, April and July 2006); and Raftilose-Synergy1, a food supplement derived from chicory, also with some supporting research conducted overseas (The British Journal of Nutrition, April 2005).

Dr. Limburg's team will treat patients at increased risk for developing colon cancer, specifically individuals age 40 or older who have advanced colorectal adenoma (precancerous tissues) or a history of colon cancer with treatment completed more than one year prior to entering the study. Tissues and blood samples will be tested pre-treatment and post-treatment to determine the preventive effects of the different medications.

Other gastroenterologists at Mayo are looking at NSAID use for patients with Barrett's esophagus. "There is evidence to support the idea that taking an NSAID will slow or reverse precancerous conditions such as Barrett's esophagus," Dr. Limburg says. "Prognosis for esophageal cancer patients is poor. We are continually looking for ways to prevent this and other cancers from ever starting, and NSAIDs provide a promising avenue for our research."

Individuals eligible for the esophageal cancer prevention study will receive esomeprazole (Nexium), an acid reflux medication, and aspirin, an NSAID. Mayo's doctors hope that using the acid reflux medication will diminish inflammation caused by acid reflux and that the aspirin will continue the healing and prevention process. Tissue in the esophagus will be tested before and after treatment to determine the benefits, if any.

The lung cancer prevention study is directed at current or former heavy smokers, age 45 or older, who are in generally good health. Those in cancer remission may be eligible to participate, if their last treatment was at least one year ago. This study is also using sulindac, which will be administered to patients with abnormal, precancerous tissues in their lungs. Pre-drug and post-drug treatment tests will determine effectiveness by reviewing the degree of abnormality of the patients' lung tissues after treatment.

"We have high hopes for all of these studies," says Dr. Limburg. "Previous work has shown that these are promising prevention avenues to pursue, and, if positive, the findings could result in substantial benefit to patients and society from a decreased cancer burden."

Mayo Clinic Cancer Center is offering the clinical studies under the auspices of membership in the Cancer Prevention Network (CPN). Dr. Limburg is the primary investigator for CPN, which is a consortium of 35 community clinics, hospitals and medical centers throughout the United States and Canada. Mayo is the lead organization and research data center for the Cancer Prevention Network, which focuses much of its research efforts on the most wide-spread and deadliest cancers.
http://www.medilexicon.com/medicalnews.php?newsid=57822∞

Whole-Body Scans May Provide Option For Diagnosing Colorectal Cancer

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10 Dec 2006

Preliminary research suggests that whole-body PET and CT scans could provide a suitable method for diagnosing the stage of colorectal cancer, according to a study in the December 6 issue of JAMA.

Colorectal cancer accounts for a large number of tumor-related deaths. Exact and complete information on the stage of the tumor is of great benefit to patients, according to background information in the article. Determining the stage of colorectal cancer often requires a multimodality, multistep imaging approach. Complete "conventional" staging determination requires additional imaging procedures to assess potential metastatic spread to lymph nodes and solid organs. Colonography combining the imaging procedures of positron emission tomography (PET) and computed tomography (CT) provides whole-body tumor staging in a single session.

Of conventional imaging procedures, contrast-enhanced CT is the most common for both the abdomen and the thorax. However, CT offers only form and structure data for the evaluation of the tumor stage. Combined PET/CT scanners have been introduced into clinical practice to provide additional information on a tumor. By performing PET/CT colonography as a whole-body imaging procedure, multimodality diagnostic workup can be shortened.

Patrick Veit-Haibach, M.D., of University Hospital Essen, Germany, and colleagues evaluated the diagnostic accuracy of whole-body PET/CT colonography for 47 patients with colorectal cancer and compared those findings with the accuracy of conventional CT staging alone and CT followed by PET (CT + PET). Patients with clinical findings and optical colonoscopy that suggested primary colorectal cancer were enrolled between May 2004 and June 2006. Patients underwent whole-body PET/CT colonography 1 day after colonoscopy. Fifty lesions were detected in the 47 patients.

Based on a lesion-to-lesion analysis, TNM stage (different classifications of tumor stage) was correctly determined by PET/CT colonography in 37 (74 percent) of 50 lesions and by CT alone in 26 (52 percent) of 50 lesions at a certain threshold of measurement. With CT + PET, TNM was correctly determined in 32 (64 percent) of 50 lesions. Compared with optimized abdominal CT staging alone, PET/CT colonography was more accurate in defining TNM stage (difference, 22 percent), which was mainly based on a more accurate definition of the T-stage.

Of the 47 patients, PET/CT colonography changed the therapy management in 4 (9 percent) compared with conventional staging. The change in patient management was based either on a more accurate assessment of the tumor stage of colorectal cancer or on accompanying findings on PET/CT colonography.

"In addition to optical colonoscopy, whole-body PET/CT colonography as an all-in-one staging modality seems feasible to provide an alternative to the multimodality, multistep staging in patients with colorectal cancer. - It is less time-consuming than a conventional multistep approach with CT alone (abdomen and thorax) and PET imaging if required. Thus, it represents a psychological and physical advantage when considering the burden to the patient of different imaging procedures. The referring physician will receive a single report including complete tumor staging in a single step, enabling him/her to define further therapy," the authors write.

"This preliminary report suggests that PET/CT colonography may be at least equivalent to CT + PET with respect to tumor staging in patients with colorectal cancer. The reason for a change in patient management with PET/CT colonography compared with a conventional staging concept must be attributed partially to the detection of synchronous [existing at the same time] tumors rather than to a more accurate TNM staging of colorectal cancer. Because an all-in-one staging modality has to offer both accurate TNM staging of the tumor in question and information on potentially present synchronous tumors, PET/CT colonography in conjunction with optical colonoscopy may be suitable for whole-body all-in-one tumor staging in patients with colorectal cancer," the researchers conclude.
http://www.medilexicon.com/medicalnews.php?newsid=58312∞

Natural Anti-Cancer Activity Heightened By 'Erectile Dysfunction' Drugs

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13 Dec 2006

Sildenafil and other "impotence drugs" that boost the production of a gassy chemical messenger to dilate blood vessels and produce an erection now also show promise in unmasking cancer cells so that the immune system can recognize and attack them, say scientists at the Johns Hopkins Kimmel Cancer Center.

Tests at Hopkins on mice with implanted colon and breast tumors showed that tumor size decreased two- and threefold in sildenafil-treated animals, compared to mice that did not get the drug. In mice engineered to lack an immune system, tumors were unaffected, proof of principle, the scientists say, that the drug is abetting the immune system's own cellular response to cancer.

In a report published in the Nov. 27 issue of the Journal of Experimental Medicine, the Hopkins team says boosted levels of the chemical messenger nitric oxide appear to dampen the effects of a specialized cell that diverts the immune system away from tumors, allowing swarms of cancer-attacking T-cells to migrate to tumor sites in the rodents.

Lab-grown cancer cells treated with sildenafil showed similar results, as did tissue samples taken from 14 head and neck cancer and multiple myeloma patients.

Sildenafil, marketed under the trade name Viagra, is one of a class of drugs used to treat erectile dysfunction in millions of men, and in recent years, its ability to stimulate the production of NO has been investigated by experts in diseases linked to the activity of blood vessels and blood components.

The new Hopkins study homes in on a tactic used by cancers to avoid detection by the immune system by turning elements of that system to its own advantage, says Ivan Borrello, M.D., assistant professor at the Johns Hopkins Kimmel Cancer Center.

Borrello and his colleagues found that tumors exploit nitric oxide-producing immune cells to create a sort of "fog" that keeps them hidden from white blood cells (T-cells) that mount attacks on tumors.

These NO-producing cells, a.k.a. myeloid-derived suppressor cells (MDSCs), normally use nitric oxide to help bring the immune system back down to surveillance levels after an "attack mode" response to foreign material.

The impotence drugs seem to reverse this process, stopping the production of nitric oxide by MDSCs thereby allowing other immune cells to "see" the cancer and attack it, says Paolo Serafini, Ph.D., a research fellow in Borrello's laboratory and lead author on the paper.

Nitric oxide is infamous among city dwellers as a component of air-polluting smog, but is gaining importance in medical research for its cell-signaling duties and its ability to divert soldiering T-cells that patrol and protect.

The Hopkins team also analyzed gene expression patterns of the myeloid-derived suppressor cells and found that sildenafil blocked two genes regulating enzymes -- arginase and nitric oxide synthase -- which are key to triggering immune suppression via MDSCs. Borrello's team found that the arginase enzyme, which metabolizes a dietary supplement called L-arginine, also contributes to dampening the immune system through MDSCs much like nitric oxide, and its production can be reversed by sildenafil.

"Impotence drugs won't cure cancer," Borello cautioned, "but could be used in addition to standard chemotherapy or immunotherapy treatments."

The investigators are planning human studies to begin in the next year.
http://www.medilexicon.com/medicalnews.php?newsid=58508∞

For Best Survival Benefits In Colorectal Cancer Patients, Follow-Up Endoscopic Surveillance Essential

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18 Mar 2007

Colorectal cancer patients who undergo colonoscopic surveillance during follow-up after surgery experience improved survival, according to a study to be published in the April issue of Clinical Gastroenterology and Hepatology but currently available on-line. Results of the study suggest that colorectal cancer patients should undergo routine colonoscopic surveillance at one year after their surgery and that more intensive surveillance may be needed in patients found to have advanced neoplasia as well as those with a prior history of adenomatous colon polyps.

"The results of our study provide additional evidence that colorectal cancer survivors benefit from surveillance with colonoscopy, and it appears that the initial surveillance colonoscopy should be performed at one year after colon resection because of the significant risk of additional cancers and polyps in these patients," according to Stephen J. Rulyak, MD, MPH, lead author of the study and Acting Assistant Professor in the Division of Gastroenterology at the University of Washington in Seattle.

The study included a total of 1,002 patients identified from the Group Health Cooperative, a large health system in Washington State, and consisted of equal proportions of men and women, the majority of whom were aged 60 years or older. More than 700 (70 percent) were alive at the end of the study period and the cumulative survival for the study group was 96 percent at one year and 68 percent at five years.

Patients who underwent one or more colon examinations during follow-up had improved survival compared with patients who did not undergo examination (652 patients versus 350 patients). Patients' estimated five-year survival was similar regardless of whether the initial follow-up colon exam was performed within 18 months of diagnosis (78.0 percent), between 18 and 35 months of diagnosis (75.5 percent) or between 36 and 60 months of diagnosis (77.3 percent). However, among patients who did not undergo a colon examination during follow-up, the five-year survival was at least 45 percent lower (52.5 percent).

Twenty patients in the study (3.1 percent) were diagnosed with a second colorectal cancer, including nine cancers detected within 18 months of initial cancer diagnosis. Advanced neoplastic polyps were also more common (15.5 percent) when the initial colonoscopy was delayed until 36 to 60 months after diagnosis compared with patients who had an initial colonoscopy within 18 months (6.9 percent). Patients with a prior history of adenomas were more likely to have advanced neoplastic polyps on follow-up. In addition, patients with advanced neoplastic polyps on the initial surveillance colonoscopy were frequently found to have advanced neoplasia on subsequent colonsocopies (81 percent).

"The best prevention we have against colorectal cancer is screening. All individuals over the age of 50 or those with a family history of the disease should be screened for this deadly disease," according to Charles Mel Wilcox, MD, Editor-in-Chief, Clinical Gastroenterology and Hepatology, and professor of medicine, University of Alabama, Birmingham. "This study provides further proof of the value of screenings and the lives that can be extended and saved."

Colorectal cancer is the third leading cause of cancer-related deaths and affects men and women equally. An estimated 112,340 new cases of colon cancer and an estimated 41,420 cases of rectal cancer will be diagnosed this year, according to the National Cancer Institute. More than 52,000 Americans will die from colorectal cancer in 2007. Colorectal cancer rates have been decreasing steadily over the past several decades due to an increase in awareness and screening.
http://www.medilexicon.com/medicalnews.php?newsid=65319∞

For Some Colorectal Cancer Patients 1 Surgery Better Than 2

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21 Mar 2007

A single surgery to remove cancer from both the colon and the liver to which it has spread may be better in some cases than the current standard treatment of two separate surgeries with chemotherapy in between, according to a study led by Duke University Medical Center researchers.

Simultaneous surgeries on the colon and liver may reduce the length of a patient's stay in the hospital and potentially lessen the risk of surgical complications without compromising long-term survival, according to the study.

"In about a third of patients who are newly diagnosed with colorectal cancer, the cancer has already spread to the liver," said Bryan Clary, M.D., a surgical oncologist at Duke and senior investigator on the study. "The standard approach for these patients has been to remove the colorectal cancer and give them chemotherapy afterwards, waiting to remove liver tumors later if patients do not appear to be developing disease elsewhere in the body. These findings suggest there might be an alternative that is as safe and may even lead to better outcomes."

Colorectal cancer is the third most common cancer in both men and women in the United States, and it is the second-leading cause of cancer-related deaths in this country.

The researchers presented their findings in a plenary session at the annual meeting of the Society of Surgical Oncology in Washington, D.C. The study was funded by the National Institutes of Health and Duke's Department of Surgery.

The researchers looked at outcomes for 610 patients who had undergone either simultaneous or separate surgeries for removal of colorectal cancer from the colon or rectum and from the liver, where it had spread. The patients were treated at three academic medical centers -- Duke, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and the University of Texas M.D. Anderson Cancer Center -- between 1985 and 2006.

"We looked at factors including surgical complications and survival data among the groups and found that in certain patient groups, simultaneous surgery was as safe as separate surgeries, could shorten the length of hospital stay and might lead to fewer surgery-related complications," said Srinevas Reddy, M.D., a general surgery resident at Duke and the study's lead author.

Chemotherapy is used in addition to cancer surgery to kill cancer cells that may reside undetected in other parts of the body. Patients having separate surgeries commonly receive chemotherapy both after their initial colon surgery and then again after their liver surgery, Clary said. But the powerful drugs used in chemotherapy can have a toxic effect on other organs, including the liver, that may increase the risk of liver surgery, he said.

The researchers also discovered that chemotherapy administered after surgical removal of cancerous liver segments favorably affected survival rates, whether or not that surgery was done alone or in conjunction with colorectal surgery. Chemotherapy administered before liver surgery showed no benefits, Clary said.

The researchers found that simultaneous surgery was only as safe as standard treatment among patients who required a minimal amount of liver to be removed. But for those whose cancer was more extensive requiring larger amounts of liver to be removed, separate surgeries remain the better treatment choice.

"For patients who require a great deal of liver to be removed, the complication risks associated with such extensive surgery outweigh the benefits of doing it all at once," Clary said.

About half of patients with colorectal and liver tumors could be eligible for the simultaneous surgery, which could translate to about 25,000 patients per year, he said.

"This study is important because it shows that patients with liver metastases at the time of their original colorectal cancer diagnosis might benefit from evaluation at a multidisciplinary center that includes not only medical oncologists and surgical oncologists skilled in colorectal surgery, but also surgeons capable of performing liver surgery," Clary said.
http://www.medilexicon.com/medicalnews.php?newsid=65517∞

Amgen Discontinues Vectibix(TM) Treatment In PACCE Trial Evaluating Vectibix(TM) As Part Of Triple Combination Regimen

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26 Mar 2007

Amgen (NASDAQ: AMGN) today announced that it has discontinued Vectibix(TM) (panitumumab) treatment in the PACCE trial evaluating the addition of Vectibix to standard chemotherapy and Avastin(R)(bevacizumab) for the treatment of first-line metastatic colorectal cancer (mCRC). The PACCE trial investigated a treatment regimen that used dual biologics combined with oxaliplatin- or irinotecan-based chemotherapy. This regimen is not currently used in clinical practice.

The decision to discontinue Vectibix treatment in the trial was based on a preliminary review of data from a pre-planned interim efficacy analysis scheduled after the first 231 events (death or disease progression). This analysis revealed a statistically significant difference in progression-free survival in favor of the control arm. An unplanned analysis of overall survival also demonstrated a statistically significant difference favoring the control arm. Additional analyses are ongoing, and Amgen plans to present the results at an upcoming scientific forum.

"Patient safety is Amgen's top priority. For this reason, we have decided to discontinue Vectibix treatment in the PACCE trial while we complete additional analyses of these preliminary results. We had hoped that adding Vectibix to the current U.S. standard-of-care for patients newly-diagnosed with mCRC would improve outcomes without excessive added toxicity. Unfortunately, it appears that adding Vectibix to Avastin, when used in combination with oxaliplatin- or irinotecan-based chemotherapy, increased toxicity, without improving efficacy," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen.

Amgen has notified the FDA and study investigators that patients who are still receiving treatment in the PACCE study should discontinue Vectibix treatment. Patients will have the option of continuing per protocol treatment without Vectibix.

In January 2007, Amgen informed all investigators and regulatory authorities about safety information arising from a planned interim safety analysis of the PACCE trial. A review of the interim analysis showed an increased incidence of grade 3 severe events of diarrhea, dehydration and infections in the Vectibix-treated patients. In addition, an increased incidence of pulmonary embolism was observed in patients who received Vectibix compared with those who did not (4 percent and 2 percent, respectively). One (<1 percent) fatal event of pulmonary embolism occurred in a patient receiving Vectibix.

Amgen is continuing to explore Vectibix as a single biologic combined with chemotherapy in Phase 3 first- and second-line registrational trials. No other clinical studies are being modified at this time. However Amgen is evaluating data across all studies.
http://www.medilexicon.com/medicalnews.php?newsid=66111∞

Decision To Leave Small Colon Polyps In Place Has No Supporting Data

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01 May 2007

The American Gastroenterological Association (AGA) Institute is eager to increase the number of patients who receive screening for colon cancer. There are a variety of established screening methods that are widely available, and emerging technologies, such as computed tomography colonography (CT colonography), that are under investigation. As the medical community evaluates CT colonography, the AGA Institute offers the following comments regarding the study by Pickhardt et al published in Cancer on the cost-effectiveness of colorectal cancer screening with CT colonography and the impact of not reporting diminutive lesions.

"To date, there are no long-term, adequately controlled studies that define whether leaving small polyps is truly safe. The science is not there, and only anecdotal conclusions can currently be made," says John I. Allen, MD, MBA, AGAF, incoming chair of the AGA Institute Clinical Practice & Quality Management Committee. "We are especially concerned as more literature emerges about small, flat, right-sided polyps. These were traditionally called hyperplastic polyps but now are recognized to be sessile serrated polyps that have a malignant potential. Radiologic imaging would not be expected to detect these polyps. This should remind us all of the need for meticulous evaluation, slow withdrawal and inspection of the proximal colon during optical colonoscopy."

The AGA has asked the National Institutes of Health to pursue a study to establish the clinical significance of diminutive polyps (<5mm) using adequate controls and long term follow up.

"The need to define the natural history and biological significance of small polyps is central to refining colorectal cancer screening, irrespective of modality," says Joel V. Brill, MD, AGAF, incoming chair of the AGA Institute Practice Management & Economics Committee. "We support any technology that helps more patients get screened for colorectal cancer. However, in the rush to increase screening rates, we cannot lose sight of the importance of providing patient care that is based on evidence. Right now, the data to support leaving small polyps in place is lacking."

CT colonography is an emerging technology that shows promise, but it is not widely available. Medicare and most insurance companies do not cover the test for colon cancer screening. Many practical issues associated with CT colonography still need to be addressed - including standardization of test performance, patient preparation and interpretation of test results - before CT colonography can be recommended for routine clinical practice. If a polyp that needs removal is found during CT colonography, the patient must then undergo a colonoscopy. Some patients might find it more convenient to have a single definitive optical colonoscopy. Additionally, after a patient has a negative colonoscopy, there are studies that show that it is possible to wait for 10 years for subsequent screening. There is no information on whether it is safe to wait 10 years between CT colonographies.

"Patients should not put off screening for colorectal cancer and polyps. All adults should discuss options with their physicians and be certain of their life-time risk for colon cancer. People with a family history that includes colon cancer are at higher risk, as are certain racial and ethnic populations and people with inflammatory bowel disease or previous colon polyps or cancer. By age 50, all adults should undergo one of the colorectal cancer screening tests currently available to them," says Dr. Allen.

Guidelines of multiple agencies and professional societies, including the AGA Institute, underscore the importance of screening for all individuals 50 years of age and older (younger for certain groups known to be at higher risk). Currently, there are several tests that may be used to screen for colorectal cancer, the second-leading cause of cancer deaths in the United States. Recommended tests include colonoscopy, flexible sigmoidoscopy, fecal occult blood test and barium enema.
http://www.medilexicon.com/medicalnews.php?newsid=69160∞

Almac Diagnostics Announces Pioneering Genetic Research On Colorectal Pre-malignancies

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08 Apr 2007

Recently Almac Diagnostics announced a major study analysing colorectal polyp tissue samples using its novel Colorectal Cancer DSA? microarray. The DSA? research tool focuses on the transcriptome of an individual disease, in this case colorectal cancer, and contains significant additional data, relevant to the disease of interest that is not available on other generic microarrays. The study will be conducted in collaboration with leading genetic researchers at Massachusetts General Hospital (MGH) (in the US).

"Our novel technology has been developed to help researchers reduce discovery timelines, accelerate the validation process and ultimately deliver clinical applications in this disease setting. For researchers, our technology provides a comprehensive, long term, stable research platform," said Paul Harkin, BSc, PhD, Professor of Molecular Oncology at the Centre for Cancer Research and Cell Biology, Queen's University, Belfast and MD and President of Almac Diagnostics.

"Down the line, this particular study aims to more accurately determine the likelihood of colorectal polyps becoming cancer. Using our proprietary technology and MGH's expertise, we have a strong foundation for developing predictive signatures that can benefit patients," he added.

The study will use paraffin embedded samples and collection is currently underway. Tissue samples will be analysed by Almac Diagnostics over two years. Information derived from the study will be analysed by a joint Almac and MGH informatics team.

"Our research will use the DSA? microarray to examine the transcriptome of colorectal polyps at a greater level of specificity and to generate information that will help us draw meaningful conclusions from our data. Eventually we hope to develop a gene expression signature that will inform both surveillance and preventative protocols for colorectal cancer," said Sridhar Ramaswamy, MD, Tucker Gosnell Investigator & Assistant Professor of Medicine, Massachusetts General Hospital Cancer Center and a Principal Investigator on the study.

DSA? Technology

Almac Diagnostic's range of Cancer DSA? research tools are novel microarrays developed to enable accelerated research in discovery, development and validation and ultimately to deliver clinical applications.

As the first microarrays based around the transcriptome of an individual disease, this technology generates significantly more information, which is reliable and relevant to the disease of interest, than is available on a generic array.

Array content has been generated through a process of sequencing to redundancy the chosen tissue and disease, followed by extensive bioinformatics analysis to create and annotate the unique, comprehensive coverage of disease and tissue specific transcriptomes. This provides researchers with all the information required to draw meaningful conclusions from their experimental data.

Based upon the gold standard Affymetrix GeneChip? technology, the DSA? research tools provide multiple independent measurements for each transcript and content is both reliable and reproducible.

The Colorectal Cancer DSA? research tool contains 61,528 probesets covering 52,306 colorectal expressed transcripts:

* 21,968 (42%) are present in the human RefSeq database

* 26,676 (51%) of transcripts are not present in the human RefSeq database

* 7% of the content represents expressed antisense transcripts to annotated genes

To date, Almac Diagnostics has launched Colorectal Cancer DSA? and Breast Cancer DSA?. Lung Cancer DSA? will be launched in June, and Ovarian Cancer DSA? and Prostate Cancer DSA? will be launched later this year. A pipeline of tests and applications of DSA? research tools in other disease areas is under development. v
Clinical Application of the Colorectal Cancer DSA? Research Tool

The successful clinical application of the Colorectal Cancer DSA? research tool was first demonstrated in colorectal cancer as a prognostic signature in stage II colorectal cancer to identify patients at high risk of relapse post surgery. Results from this study were presented at the American Society of Clinical Oncology (ASCO) annual meeting in 2006.

Application of this technology provides clinically relevant data that may ultimately improve patient care in a wide range of contexts including companion diagnostics, biomarker discovery and patient stratification.

The Vital Role of Research on Colorectal Pre-Malignancies

Colorectal cancer is the second most frequent malignancy in affluent societies. More than 940,000 cases occur annually worldwide and nearly 500,000 die from the disease each year. Most colorectal cancers begin as polyps or adenomas, growths attached to the inside of the colon or rectum. Colorectal polyps commonly occur, but most of them do not turn into cancer.

US protocols advise screening for colorectal polyps at age 50 years, with followup surveillance anywhere from two years to ten years afterwards, while the NHS Bowel Cancer Screening Programme offers screening every two years to all men and women aged 60 to 69. The aim is to detect bowel cancer at an early stage, when treatment is more likely to be effective. However, these screening programmes represent a significant burden to both patients and healthcare systems. In addition, even with intensive surveillance programmes, there is still the possibility that colorectal cancer can go undetected.
http://www.medilexicon.com/medicalnews.php?newsid=67220∞

An Aspirin A Day Keeps Colorectal Cancer Away

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11 May 2007

Long term use of 300 mg or more of aspirin a day for five years can prevent colorectal cancer, conclude authors of a study published in this week's special gastroenterology edition of The Lancet.

But the authors of the Article and an accompanying Comment stress that the potential risks of long term aspirin use at this dose and the availability of alternative prevention strategies mean that widespread use of aspirin for cancer prevention cannot be recommended in the general population.

However, the benefits are likely to outweigh the risks in individuals at increased risk of colon cancer. The findings are also likely to influence the choice of antiplatelet drug in patients who require long-term treatment because of vascular disease.

The study was conducted by Professor Peter Rothwell, University Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK and colleagues. In collaboration with the original investigators (Sir Richard Doll, Sir Richard Peto and Charles Warlow), they determined the delayed effect of aspirin by following-up patients from two large randomised trials of aspirin performed in the late 1970s and early 80s - the British Doctors' Aspirin Trial and the UK-TIA Aspirin Trial.

The researchers were particularly interested in long term follow-up due to the likely time delay in any effect of aspirin on colorectal cancer. Adenomas (the pre-cancerous growths that aspirin is thought to reduce) take at least 10 years to develop into cancers. The study showed that use of aspirin for five years reduced the subsequent incidence of colorectal cancer by 37% overall, and by 74% during the period 10-15 years after treatment was started.

In an accompanying analysis of observational studies, the risk of colorectal cancer also appeared to be reduced by between 50-70% in patients taking medium-high doses of aspirin for 10 years or more. This analysis also showed that the effects of aspirin were consistent regardless of age, sex, race or country of origin of patients studied (all of which affect the general rate of colorectal cancer) and that the effect was also seen in individuals with a family history of colorectal cancer in a first degree family relative (which increases lifetime risk of an individual acquiring the disease by two to four times).

The authors conclude: "Use of 300 mg or more of aspirin a day for about five years is effective in primary prevention of colorectal cancer, with a latency of about 10 years, which is consistent with findings from observational studies.

"Long-term follow up is required from other randomised trials to establish the effects of lower or less frequent doses of aspirin."

In an accompanying Comment, Dr Andrew Chan, Gastrointestinal Unit, Massachusetts General Hospital, Boston, USA, says: "Rothwell and colleagues' results, when viewed in the context of the preponderance of laboratory studies, epidemiological data, and adenoma recurrence trials, do provide convincing evidence that aspirin, at biologically relevant doses, can reduce the incidence of colorectal cancer.

"However, with the concerns about the potential risks of long-term aspirin use and the availability of alternative prevention strategies (e.g. screening), these findings are not sufficient to warrant a recommendation for the general population to use aspirin for cancer prevention."

www.lancet.com
http://www.medilexicon.com/medicalnews.php?newsid=70463∞

Study Reveals Aspirin's Colorectal Cancer Prevention Mechanism

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01 Jun 2007

Aspirin therapy's ability to reduce the risk of colorectal cancer, an association seen in a large number of studies, appears to depend on the drug's inhibition of the COX-2 enzyme, the action that also underlies aspirin's usefulness for treating pain and inflammation. In the May 24 New England Journal of Medicine, investigators from Massachusetts General Hospital (MGH), Dana-Farber Cancer Institute and Brigham and Women's Hospital report that regular aspirin intake only reduced the incidence of colorectal tumors that overexpress COX-2.

"We knew that aspirin can block COX-2 function and that COX-2 is present in the vast majority of colorectal tumors but not in normal colon tissue," explains Andrew Chan, MD, MPH, of the MGH Gastrointestinal Unit, the paper's lead author. "Therefore we hypothesized that, if blocking the COX-2 pathway was the mechanism underlying aspirin-associated risk reduction, it should preferentially reduce the incidence of those tumors that rely on COX-2."

To investigate that theory, the research team compiled data from two ongoing prospective research studies - the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Both studies gather comprehensive health information on their participants every two years, data which is analyzed for associations between factors such as diet and the incidence of several diseases. Both the NHS, which enrolls more than 120,000 female registered nurses, and the HPFS, following more than 50,000 men employed in the health professions, have previously found associations between aspirin intake and reduced colorectal cancer risk.

For the current study, the researchers focused on almost 83,000 NHS participants and about 47,000 HPFS participants for whom necessary information was available. They received permission to acquire medical records and pathology reports from those who had reported being diagnosed with colorectal cancer, then retrieved more than 600 pathology specimens from participants whose diagnoses could be confirmed. The samples were analyzed for expression of COX-2.

As seen in previous reports, among the more than 120,000 participants, those who took at least two standard aspirin tablets a week had about three-quarters the risk of colorectal cancer that aspirin non-users did. However, analysis of tumor samples showed that reduction in risk only applied to tumors that expressed COX-2. The incidence of COX-2-negative tumors was virtually the same among those who did and did not take aspirin.

"These results will allow us to test another hypothesis: that in patients who have had colorectal cancer or polyps in the past, expression of COX-2 in the earlier lesion might indicate those for whom aspirin could reduce the risk of recurrence," says Charles Fuchs, MD, MPH, of Dana-Farber, the study's senior author. "Answering that will be our next target."

Both researchers note that current evidence does not support generally recommending aspirin therapy to reduce colorectal cancer risk. "For most people, the best way to prevent colorectal cancer is through screening, which we know saves lives by allowing us to treat polyps before they become cancers," says Chan.

Fuchs adds, "An individual who has had colorectal cancer in the past is at higher risk for subsequent tumors, and that might be someone who should discuss the advisability of taking aspirin with his or her primary care physician. We hope that our future research will further clarify who would benefit most from regular aspirin therapy and that understanding the mechanism of this effect will lead to new preventive and treatment strategies."

Fuchs is an associate professor of Medicine at Harvard Medical School, where Chan is an assistant professor of Medicine. Study co-author Shuji Ogino, MD, PhD, is an HMS assistant professor of Pathology at Brigham and Women's Hospital. The study was supported by grants from the National Cancer Institute, the National Institutes of Health, the Bennett Family Fund for Targeted Therapies Research, the Entertainment Industry Foundation National Colorectal Cancer Research Alliance, the Marshall S. Kates Memorial Fund, and the Foundation for Digestive Health and Nutrition.

Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology and physiologic genomics, transplantation biology, and photomedicine.

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), a designated comprehensive cancer center by the National Cancer Institute.

www.massgeneral.org
http://www.medilexicon.com/medicalnews.php?newsid=72670∞

Exploring Better Ways To Determine When To Change The Course Of Treatment

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04 Jun 2007

Counting circulating tumor cells before and after the start of treatment for patients with metastatic colorectal cancer could help doctors determine when or if a change in treatment should be made. The results of a large, multicenter, international study laying the groundwork for such decisions were presented at the Annual Meeting of the American Society of Clinical Oncology. The study showed the number of circulating tumor cells, or CTC, is a significant predictor of survival and cancer progression.

Few studies have examined the relationship of CTC and a patient's prognosis in cancer. This is an important area of research in metastatic colorectal cancer because there are little data to help physicians chose which treatment is best for which patients or to determine when a change in treatment is warranted.

"If we had a way to know early on that a tumor isn't responding to a particular drug, we could switch to a different treatment before growth of the cancer is seen on a CAT scan," said Neal J. Meropol, director of the gastrointestinal cancer program at Fox Chase Cancer Center and lead investigator of the study. "If we could determine that the tumor was destined to grow after a few weeks of treatment, we'd be able alter course even before the first scan."

For this study, Meropol and his colleagues examined the association between the circulating tumor cell number and progression-free and overall survival for 430 adult patients with metastatic colorectal cancer.

The number of CTC was measured at baseline, one month, and several other points after the start of treatment. CTC were isolated and counted by an immunomagnetic cell separation technique, an FDA-approved technology developed by Immunicon Corporation (Nasdaq-Global Market: IMMC}. CT scans were obtained in usual practice at baseline and every 6-12 weeks after starting treatment.

Having 3 or more CTC (per 7.5 mL of blood) was defined as "unfavorable" in an initial analysis. Patients with fewer than 3 CTC were considered favorable.

Before initiation of the first treatment (baseline), 53 percent of patients had no detectable CTC. These patients had superior median survival times compared with those patients who had circulating tumor cells. A favorable CTC number before treatment is associated with better progression free survival and overall survival.

In addition to its predictive value at baseline, the CTC was also a strong indicator of prognosis as early as 3-5 weeks after treatment initiation.

"Patients with unfavorable CTC had a shorter median survival time. This was even seen in those patients whose CT scan the gold standard for tumor evaluation- indicated no disease progression," Meropol explained.

The median overall survival of patients with a favorable CTC before treatment was almost double that of those with an unfavorable CTC (18.5 months vs. 9.4 months). Patients with a favorable CTC had a median progression free survival of 7.9 months and those with an unfavorable CTC had a progression free survival of 4.5 months. The measurement of CTCs consistently provided prognostic information even when tested at 6-12 weeks.

Another key finding was the predictive value of a change in CTC. Among patients with unfavorable CTC at baseline, those whose numbers decreased after treatment to fewer than 3 had improved progression-free survival and overall survival.

"Potentially, this tool could be useful in the clinic to make real-time decisions about whether a treatment is helping. Our ultimate goal is to continue effective treatment, but spare patients the side effects of a treatment that is destined to fail. This is the direction that future studies must take"

Fox Chase Cancer Center was founded in 1904 in Philadelphia as the nation's first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at http://www.fccc.edu∞.

Abstract #4010- Circulating tumor cells (CTC) predict progression free (PFS) and overall survival (OS) in patients with metastatic colorectal cancer. Oral Presentation - Gastrointestinal (Colorectal) Cancer - E Arie Crown Theater

Fox Chase Cancer Center
7701 Burholme Ave.
Philadelphia, PA 08065
United States
http://www.fccc.edu∞
http://www.medilexicon.com/medicalnews.php?newsid=72973∞

Sequential And Combination Chemotherapy Equally Effective In Treating Advanced Colorectal Cancer

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Article Date: 13 Jul 2007 - 1:00 PDT

Many patients with incurable advanced colorectal cancer could be offered a more gentle treatment strategy starting with a single chemotherapy drug, as an alternative to current standard initial combination chemotherapy, without compromising their survival. These are the conclusions of authors of two separate Articles published in this week's edition of The Lancet.

They believe their results challenge conventional clinical practice in this area; however, an accompanying Comment says that evidence supports the continuing use of initial combination chemotherapy.

Colorectal cancer causes over half a million deaths every year worldwide. This death toll could fall with advances in prevention, screening and treatment - but there are many patients in which controlling the cancer sufficiently to delay death and reduce symptoms is the only realistic therapeutic goal.

In the first Article, Professor Matt Seymour, University of Leeds and the Gastrointestinal Research Unit, Cookridge Hospital, Leeds, UK and colleagues at the UK National Cancer Research Institute discuss the results of the Medical Research Council FOCUS Trial. This trial is the largest randomised clinical trial ever conducted in the treatment of advanced colorectal cancer, and involved 2135 patients divided into three groups. The first group received single-drug treatment with fluorouracil for as long as it controlled their disease, followed by single-drug treatment irinotecan. The second group received fluorouracil followed by combination treatment (fluorouracil plus irinotecan or oxaliplatin), while the third group received combination chemotherapy from the outset.

The researchers found that patients in the first group had the shortest survival, but the second and third groups had similar overall survival. Toxic effects were lowest during the single-treatment fluorouracil, and quality of life scores were similar throughout all the treatment regimens.

The authors conclude: "This large randomised trial has produced a surprising result which challenges accepted standard treatment approaches in advanced colorectal cancer therapy." For the larger number of patients with more extensive metastases who will not be cured, they add: "FOCUS offers an important choice, informed by the knowledge that a decision to opt for staged treatment approach, starting with less toxic therapy and keeping active agents in reserve, entails minimal, if any, compromise in survival."

In the second Article, Professor Cornelis Punt, Department of Medical Oncology, Radboud University Nijmegen Medical Centre, The Netherlands, and colleagues report the results of the CAIRO trial. In this study, 820 patients were randomly assigned to receive either sequential treatment with capecitabine, irinotecan and oxaliplatin; or combination treatment of capecitabine plus irinotecan followed by capecitabine plus oxaliplatin. They found that median overall survival rates were similar in the two groups. Previous studies have shown at least similar efficacy and a favourable toxicity profile for capecitabine when compared with fluorouracil.

The authors conclude: "Our results show that, for patients with advanced colorectal cancer, combination treatment with all effective cytotoxic drugs was no better than their sequential use. Progression-free survival over all subsequent treatment lines was not significantly different between the study groups. Additionally, sequential treatment was associated with less toxicity during first-line treatment than was combination therapy."

"Chemotherapy remains the backbone of systemic treatment in this disease, and our results indicate that sequential treatment remains a valid treatment option for these patients."

In the accompanying Comment, Dr Hans-Joachim Schmoll, Martin-Luther University, Halle, and Dr Daniel Sergeant, Mayo Clinic, Rochester, Minnesota, USA, say: "Clinically validated prognostic and predictive factors, such as genomic tests, are needed to define in which patients more intensive therapy is worthwhile, and ideally, which specific treatment should be used.

"Until then, to maximise potential benefit for each patient, an approach based on prognosis and disease presentation with initial combination chemotherapy for most patients, reserving single-agent fluorouracil for a subgroup with less aggressive or never-resectable disease, should be the standard of care for first-line treatment of metastatic colorectal cancer.

"FOCUS and CAIRO support the use of first-line single agent fluorouracil for the latter subgroup of patients and therefore provide an ethical basis for investigating novel drugs in combination with single-agent fluoropyrimidines in future trials, to further develop the treatment armamentarium for patients with colorectal cancer."

http://www.lancet.com∞
http://www.medicalnewstoday.com/articles/76625.php∞

Chemotherapy For Advanced Colorectal Cancer Prolongs Survival Of Patients

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Article Date: 20 Sep 2007 - 0:00 PDT

Modern chemotherapy treatment for advanced colorectal cancer, such as irinotecan, oxaliplatin, and molecular-targeted treatments, are successful in extending the lives of patients by several months - not the case a few years ago when these treatments were unavailable, says a report in The Lancet Oncology September 20th Edition.

Professor Loennidis, University of Ioannina School of Medicine, Greece, and team comment that while prior studies indicated that newer therapies were beneficial, how beneficial they really are was never that clear. The scientists wanted to find out whether some regimens were linked to improved survival rates and delayed disease progression. They also wanted to assess the magnitude of these benefits.

They examined 242 randomized trials to compare systemic treatment regimens in advanced colorectal cancer patients during the last four decades.

The scientists report that for patients who had been expected to survive for one year on fluorouracil and leucovorin, the estimated absolute survival benefit of additional treatment with irinotecan + bevacizumab was eight months - in other words, irinotecan plus bevacizumab gave patients an extra eight months. Patients survived for an extra 4.7 months with the addition of oxaliplatin + bevacizumab or irinotecan + oxaliplatin.

The authors explained that as newer and more intensive treatments have higher toxicity this type of quantification is required to ascertain the incremental survival benefits of each type of chemotherapy compared to older treatments so that toxic effects can be weighed up against improved efficacy.

Although patients are surviving for longer, multidrug combinations often have serious toxic effects, caution the authors. They say additional and longer-term follow-up data on toxicity in different settings is required on these new regimens. "The fluorouracil, leucovorin, irinotecan, plus bevacizumab regimen especially, which has the highest probability to be the best in improving survival according to our analysis, might be complicated by up to 84?9% of grade 3 or 4 adverse events, including a 1?5% chance of gastrointestinal perforation. Existing uncertainties suggest that more data are needed, especially for the newest regimens."
http://www.medicalnewstoday.com/articles/83002.php∞

Kaiser Permanente Study Shows Under Used Colon Cancer Screening Test Is Effective

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Article Date: 26 Sep 2007 - 0:00 PDT

An under used colon cancer screening test now available in the U.S. effectively detects colorectal cancer and may help to improve colon cancer screening rates, according to investigators at the Kaiser Permanente Division of Research. The study appears in the September 25, 2007 issue of the Journal of the National Cancer Institute (JNCI).

Improved Fecal Occult Blood Tests (FOBT) called Fecal Immunochemical Tests (FITs), look for human blood in the stool and are more effective at detecting cancers and polyps than the older and more widely used stool screening tests -- the guaiac tests (GTs), said James Allison, MD, an adjunct investigator with the Kaiser Permanente Division of Research, UCSF Clinical Professor of Medicine Emeritus and lead author of the study.

Investigators and gastroenterologist clinicians at Kaiser Permanente's Northern California Division of Research compared the performance of FIT and a sensitive GT in 5,841 people with an average risk for colorectal cancer and looked at the tests' ability to detect colorectal cancers and polyps in people with the disease (sensitivity) and the tests' ability to determine which people do not have the disease (specificity).

The FIT had a sensitivity of 81.8% for detecting colorectal cancers and a specificity of 96.9%. The GT was 64.3% sensitive for detecting colorectal cancers and 90.1% specific. The higher specificity of the FIT means that there are fewer false positive results and, therefore, fewer interventional procedures need to be performed in patients without disease, said the researchers.

"FIT is an important and a welcome addition to our screening tool kit, especially because according to the National Cancer Institute, colorectal cancer screening rates continue to lag well behind those for other cancers. All recommended screening tests are effective tools for detecting colorectal cancer early, when it is highly curable," said Allison. "No screening test is perfect, but any is better than none, and ultimately, the best screening test is the one the patient actually completes." FIT is convenient for patients because it is easy to prepare and complete at home and does not involve dietary restriction, explained the researchers.

FIT is more specific than the sensitive GT for detecting cancers and polyps because it detects human blood in the stool. The GT, on the other hand, detects peroxidase activity found in both human and non-human blood as well as in many vegetables such as broccoli and horseradish. This can lead to more false positives, explained the researchers.

FIT has other advantages as well, according to the researchers. Some FITs can be developed and interpreted by lab equipment. This innovation allows for management of large numbers of tests in a standardized manner with excellent quality assurance, they explained.

The study was funded by the National Cancer Institute, American Digestive Health Foundation Outcomes Research Training Award, Kaiser Foundation Health Plan Community Benefit Program, The Permanente Medical Group Innovation Program; Beckman Coulter, Inc., and Enterix Corporation.

Additional authors on this study include Theodore R Levin, Jo P. Tucker, Irene S. Tekawa, Wei K. Zhao, and Joseph Selby all from the Kaiser Permanente Division of Research in Oakland, Ca; Albert M. Palitz, from the department of gastroenterology, Kaiser Permanente Medical Center in Walnut Creek; Lori C. Sakoda, department of epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle; Thomas Cuff, department of medicine, Kaiser Permanente Medical Center in Richmond, CA; Mary Pat Pauley, department of medicine Kaiser Permanente Medical Center, Sacramento; Lyle Shlager, department of internal medicine Kaiser Permanente Medical Center, San Francisco; J. Sanford Schwartz, department of medicine, University of Pennsylvania; David F. Ransohoff, departments of medicine and epidemiology, University of North Carolina at Chapel Hill.
http://www.medicalnewstoday.com/articles/83628.php∞

Molecular Profiling Can Accurately Predict Survival In Colon Cancer Patients

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Article Date: 27 Sep 2007 - 17:00 PDT

Researchers in The Netherlands have developed a method of accurately predicting which patients with colon cancer are most likely to have their disease recur after surgery and who would, therefore, be likely to benefit from additional chemotherapy.

Led by Professor Rob Tollenaar at Leiden University Medical Center and Dr Laura Van 't Veer at The Netherlands Cancer Institute, they have analysed for the first time the different expressions of genes in the entire genome of tumour tissues from 121 patients with stage II colon cancer who had not received adjuvant chemotherapy.

Prof Tollenaar, who is head of sections endocrine, gastrointestinal and oncologic surgery in the department of surgery, told a news briefing at the European Cancer Conference (ECCO 14) in Barcelona, today (Tuesday) that the full-genome molecular expression profiling had identified two groups of patients that had distinct clinical outcomes.

"Patients with stage II colon cancer have an overall five-year survival of about 80%," he explained. "So far, no randomised clinical trials has shown significant benefit from giving adjuvant chemotherapy. Three-quarters of patients are cured by surgery alone and, therefore, less than 25% of patients would benefit from additional chemotherapy.

"Our analysis showed a cluster of 75% of the patients, of whom approximately 90% were likely to survive for at least five years with no distant metastases. In the second cluster of the remaining 25% of the patients, only about 65% of them had five-year survival without distant metastases, and this is the group who would be likely to benefit from adjuvant chemotherapy.

"This is the first time that the identification of a poor survival group has been based on genome-wide expression analysis and, therefore, it relates tumour biology more accurately to the outcome of disease."

Further analysis of the results showed that patients in the "poor outcome" group were over three times (3.2) more likely to develop metastases than the patients in the "good outcome" group. This method of identifying "poor outcome" patients was better at predicting which patients should have adjuvant chemotherapy than the commonly-used method that follows recommendations from the American Society of Clinical Oncology (ASCO).

The researchers checked their findings against information from another set of colon cancer patients that had been published in the Journal of Clinical Oncology in 2005. Prof Tollenaar said: "In these stage II colon cancer patients, the five-year metastasis-free survival prediction was confirmed; for the good outcome group, five-year survival was 90% and for the poor outcome group it was 40%. This was important validation of our own results."

From the genome-wide analysis, the researchers identified a subset of 100 genes that were able to predict outcome equally as well as the full-genome molecular expression profile. Many of these genes are know to regulate the Epithelial-Mesenchymal transition (EMT) - a programme of cell development that is thought to be a driving force behind the development of metastases in colorectal cancer.

Prof Tollenaar said that although his research predicted outcome of disease in patients who had not received adjuvant chemotherapy, more work would need to be done to identify the molecular profile for those patients who would actually benefit from chemotherapy.

Before the results of this research could start to be used in the clinic, Prof Tollenaar said two things needed to happen: "Current, ongoing validation studies required to confirm our findings have to be completed, and the test needs to be developed into a robust diagnostic device. The molecular profiling company Agendia BV of Amsterdam has taken this up and it is likely to be available in early 2008."

As to whether these findings would save large numbers of colon cancer patients from unnecessary chemotherapy, Prof Tollenaar said: "This depends greatly on the current practice in different European countries. For example, in Spain 60% of stage II colon cancer patients receive adjuvant chemotherapy, while in The Netherlands only 20% do. So in some countries it will result in a decrease in the number of patients receiving chemotherapy and in others, an increase; but both outcomes will result in a more accurate selection of patients."

http://www.fecs.be/∞
http://www.medicalnewstoday.com/articles/83725.php∞

Patients With Chronic Conditions In Addition To Colon Cancer Still Benefit From Chemotherapy

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Article Date: 29 Sep 2007 - 1:00 PDT

Patients with chronic conditions such as diabetes and heart failure benefit just as much from adjuvant chemotherapy after surgery for colon cancer than patients without these conditions - although they are less likely to receive this extra treatment, according to an analysis of drug treatment and outcomes in patients with colon cancer, published in Cancer this month.

Most patients who are diagnosed with colon cancer have at least three different chronic conditions in addition to their cancer diagnosis because they are generally at an age when chronic conditions are more prevalent. These diagnoses are important because patients with comorbidities are less likely to survive for a long time after cancer than those without, and evidence also suggests that physicians are less likely to recommend chemotherapy for such patients, believing it might adversely affect outcomes. However, while this assumption is often made in clinical decision-making, accurate information about how specific conditions affect choices of care or outcomes is scarce.

The only available evidence is from studies that look at comorbid conditions as a single group, rather than teasing out how specific disorders affect outcomes. This information dearth leaves physicians unable to assess the real risks and benefits of adjuvant treatment in individual patients. Evidence from clinical trials suggests that adjuvant chemotherapy is associated with a 34% reduction in mortality and this benefit does not diminish with increasing age. However, increasing age
which equates to increasing prevalence of chronic conditions
is associated inversely with the receipt of adjuvant therapy.

To investigate how patients with colon cancer are affected by non-cancer illness, Cary Gross and colleagues from Yale University School of Medicine did a population-based study of older patients with stage III colon cancer. "Specifically, we determined the degree to which specific conditions affected the probability of receiving adjuvant chemotherapy from 1995 to 1999 as well as the risks and benefits of therapy," the authors explain.

Using the US SEER (Surveillance, Epidemiology, and End Results) database, which is a tumour registry linked into records of patients who receive government-financed treatment in the USA , the researchers identified all patients older than 67 years who were diagnosed with primary adenocarcinoma of the colon between 1993 and 1999. After excluding patients who did not receive adjuvant chemotherapy because of a very poor prognosis, the team was left with a sample size of 5330 patients. They identified the presence of comorbid conditions by tracing claims through Medicare, the US insurance programme for older people, for any comorbid conditions made from 2 years before a cancer diagnosis up to 30 days afterwards.

Of the final study sample, 60.3% of patients had received adjuvant therapy, and, as expected, the probability of a patient being offered this treatment decreased with increasing age and the total number of comorbid conditions. The total number of chronic conditions was related strongly to the receipt of chemotherapy. Overall, 69.1% of patients with no conditions received treatment compared with just 38.6% of patients with greater than three conditions received treatment.

When these figures were broken down by the three most common comorbid disorders
heart failure, which affected 16% of the group, chronic obstructive pulmonary disease (18%), and diabetes (17.8%)
the researchers found that heart failure was most significantly related to receipt of chemotherapy: 36.2% of patients with this condition got the extra drugs compared with 64.9% of those without. The effects were more modest for the other two chronic conditions: 55.2% versus 61.5% for patients with and without chronic obstructive pulmonary disease, respectively and 58.3% versus 60.7% for patients with and without diabetes, respectively. There was no consistent relation between chronic conditions and completion of chemotherapy.

Adjuvant therapy was associated with a significant reduction in mortality in all groups, but patients who received chemotherapy and did not have heart failure had the highest survival probability. Patients who did not receive chemotherapy and did have heart failure had the lowest probability of survival. However, while chemotherapy increased the risk of hospitalisation for gastrointestinal, infectious or haematological complications for patients without heart failure, it did not do the same for patients with heart failure, suggesting that chemotherapy may increase the risk of chemotherapy-related toxicity in heart failure patients to a lesser extent that it does in patients without this disorder.

The researchers concluded that although comorbidity was associated with an increased risk of death, it did not diminish the relative survival benefit associated with treatment. What is more, the observed differences between use of chemotherapy and associated outcomes with the different conditions "emphasizes the importance of moving beyond a comorbidity index when investigating the care and outcomes of older cancer patients," say the authors. "Simply counting the number of conditions with which each patient has been diagnosed may overlook important distinctions between conditions."
http://www.medicalnewstoday.com/articles/84036.php∞

Colonoscopy Remains The Most Effective Screening Option For Colon Cancer

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Article Date: 03 Oct 2007 - 0:00 PDT

According to the American Society for Gastrointestinal Endoscopy (ASGE), colonoscopy remains the most effective screening option for colorectal cancer. Colonoscopy is widely accepted as the best method for colon cancer screening because it allows the trained physician to thoroughly evaluate the entire colon. Colonoscopy has a high detection rate for polyps, including small lesions, and the ability to remove them immediately during the procedure, rather than scheduling a second exam. Biopsies can also be taken of any abnormal areas at the same time as the screening or diagnostic test.

"Although there have been recent studies showing improvements in other colon cancer screening modalities, colonoscopy is the most effective because it is both diagnostic and therapeutic. Not only does it allow us to see the entire colon and identify polyps of all sizes, but it also allows us to remove polyps during the same exam, before they turn into cancer," said Mark Pochapin, MD, spokesperson for the ASGE. "Many colorectal cancer deaths can be prevented through proper detection. If you are over 50 or have a family history of colorectal cancer, talk to your doctor about getting screened today."

Earlier this year, the American Cancer Society announced drops in cancer deaths, which were attributed to earlier detection and improved treatment. The biggest decrease occurred in colorectal cancer deaths.

A 2006 study by Yale researchers found that, as Medicare coverage for colorectal cancer screening expanded, so did colonoscopies and with that, early cancer detection rates. The key variable in survival statistics among cancers, including colorectal, is early detection and prevention. These findings support ASGE's position that colonoscopy is the most effective screening and prevention method.

Colore