NCI Cancer Bulletin: A Trusted Source for Cancer Research News
NCI Cancer Bulletin: A Trusted Source for Cancer Research News
July 24, 2007 • Volume 4 / Number 22 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Studies Suggest More Flexibility in Treating Advanced Colorectal Cancer

The results of two new large European clinical trials challenge the conventional thinking on the initial treatment of patients with advanced colorectal cancer, particularly those undergoing treatment almost strictly for palliative purposes, the studies' leaders say.

Published in the July 14 Lancet, the trials' results suggest that using either fluorouracil or capecitabine as single agents for first-line treatment in this patient population is no less effective and potentially less toxic than using a combination of two chemotherapy drugs, as is commonly recommended in the United States and Europe.

However, several leading experts on the treatment of colorectal cancer in the U.S. and abroad cautioned against overinterpreting the trials' results, arguing that combination chemotherapy should still be the standard of care for the first-line treatment of most patients with advanced disease.

In both trials, there was no statistically significant difference in overall survival between patients treated with regimens in which either single agent was used as a first-line treatment before moving on to other chemotherapy drugs or combinations that have shown activity in this patient population, which they called a sequential or staged approach.

For patients who are undergoing treatment without curative intent, wrote Dr. Matthew T. Seymour, from Cookridge Hospital in Leeds, United Kingdom, and colleagues who led the larger of the two trials, dubbed FOCUS, the results provide "an important choice, informed by the knowledge that a decision to opt for a staged treatment approach, starting with less toxic therapy and keeping active agents in reserve, entails minimal, if any, compromise in survival."

The trials took somewhat different approaches in the staged-therapy arms, but both had one arm in which patients were randomized to combination chemotherapy for first-line treatment. FOCUS was the larger of the two, with more than 2,100 patients. The other trial, CAIRO, which used capecitabine as its single agent first-line therapy, had 820 patients.

In a commentary accompanying the trial results, Drs. Hans-Joachim Schmoll from Martin Luther University in Germany and Daniel Sargent from the Mayo Clinic cited several factors that support the limited use of a single-agent, first-line approach.

Several other clinical trials have shown that combination chemotherapy is superior to single-agent fluorouracil in improving overall survival, they wrote.

In addition, the first-line combination chemotherapy regimens used in FOCUS and CAIRO were not accepted standard regimens, which they argued was essential for any "trial designed to test a reduction in therapy."

Even in the context of palliative treatment, combination chemotherapy is most often the wisest choice, says Dr. Heinz-Josef Lenz, associate director of the Gastrointestinal Oncology Program at USC/Norris Comprehensive Cancer Center.

"The data are clear: Response rates are higher with first-line combination treatment, and progression-free survival is higher," Dr. Lenz says. That often translates into better palliation, he adds.

Use of a single agent as first-line therapy may be appropriate in some patients, advises Dr. Wasif Saif, director of the Gastrointestinal Cancers Program at Yale Cancer Center, such as those with a poor performance status and less aggressive disease in whom the intent is clearly palliation.

The trials' results "present very important options for certain patients, but," he cautions, "I still believe a lot needs to be done before we change the standard of care."

Dr. Saif stressed that identifying molecular biomarkers indicative of response to certain agents or treatments must be the highest research priority.

Dr. Lenz agreed, but explained that the pursuit of such biomarkers has been hampered by rapidly changing treatment patterns. He is hopeful, however, that there may now be a "window of opportunity" to develop and validate biomarkers for response to chemotherapy and targeted agents, primarily bevacizumab (Avastin) and cetuximab (Erbitux), which have shown a benefit in some patients with advanced colorectal cancer.

By Carmen Phillips