When administered before chemoradiation, the common anti-cancer drug cisplatin neither improved disease-free survival nor reduced the number of colostomies needed when compared to the standard treatment for patients with anal canal cancer, according to a study published in the April 23 issue of the JAMA, the Journal of the American Medical Association.
In the largest cooperative phase III randomized controlled trial of its kind, a multicenter research team led by Jaffer Ajani, M.D., professor in the Department of Gastrointestinal Medical Oncology at The University of Texas M. D. Anderson Cancer Center, compared the standard treatment regimen of fluorouracil plus mitomycin and radiotherapy to fluorouracil plus cisplatin and radiotherapy in 644 patients with anal canal cancer. The five-year disease-free survival rate was 60 percent in the mitomycin-based group and 54 percent in the cisplatin-based group. The five-year overall survival rate was 75 percent in patients receiving mitomycin versus 70 percent receiving cisplatin, with more cancer-related deaths in the cisplatin-based group (54 patients) compared to mitomycin-based group (28 patients).
Patients who received cisplatin-based treatment resulted in significantly higher rates of colostomy (19 percent versus 10 percent). It is widely held among practicing oncologists that the colostomy procedure, which creates an alternative exit from the colon to divert waste, should only be used as a last resort in the treatment of anal canal cancer due to its considerable affect on the patient's quality of life.
"Based on preliminary data from smaller trials that suggested considerable sensitivity to the fluorouracil plus cisplatin combination, cisplatin has gained popularity among oncologists as a drug to treat anal canal cancer," said Ajani. "However, it is clear from this data that cisplatin is not the drug to use and its use should be discontinued in standard therapy."
The study expanded on findings from two pilot studies that encouraged oncologists to believe that cisplatin could potentially be used to reduce the cancer in the primary tumor and lymph nodes prior to administration of concurrent chemoradiation. The research group hypothesized that using cisplatin to downsize the tumors first could be an effective strategy for treating the disease because previous studies have established that chemoradiation is more effective for smaller anal canal carcinomas than larger ones.
"There have been incremental advancements in the treatment for anal canal cancer in the last decade and there was hope that the unique cisplatin-based strategy would offer an improved, less-toxic therapy to patients suffering from the disease," Ajani said. "While our research did not uncover a new standard of treatment, comparative studies such as this one are imperative to determining best practices and informing community oncologists."
According to the American Cancer Society, an estimated 5,070 new cases of anal canal cancer will be diagnosed in 2008. The five-year disease-free survival of approximately 65 percent has not improved since the early 1990s. Primary anal canal tumor size has a direct bearing on cure rates, and the five-year survival rates decrease significantly for tumors larger than 5 cm diameter. Approximately 25 percent of newly diagnosed anal carcinomas are larger than 5 cm in diameter.
From this study, it is anticipated that researchers will look to explore other options such as newer targeted therapies and intensity-modulated radiation plus concurrent chemotherapy to improve disease-free and colostomy-free survival relative to the continued standard of concurrent chemoradiation with fluorouracil and mitomycin.
This study was part of the U.S. Gastrointestinal Intergroup trial RTOG 98-11. In addition to Ajani, researchers contributing to the study include Kathryn A. Winter, M.S., Radiation Therapy Oncology Group; Leonard L. Gunderson, M.D., Mayo Clinic, Scottsdale, Arizona; John Pedersen, M.D., Cross Center Institute, Edmonton, Alberta, Canada ; Al B. Benson III, M.D., Northwestern University, Chicago, Illinois; Charles R. Thomas Jr., M.D., University of Oregon, Portland; Robert J. Mayer, M.D., Dana-Farber Cancer Institute, Boston, Massachusetts; Michael G. Haddock, M.D., Mayo Clinic, Rochester, Minnesota; Tyvin A. Rich, M.D., University of Virginia, Charlottesville; Christopher Willett, M.D., Duke University, Durham, North Carolina.