An article published in JAMA reports that for patients with anal canal cancer, experimental chemotherapy treatment with the drug cisplatin (administered prior to other treatments) failed to increase disease-free survival rates. Compared to the standard treatment regimen, therapy with cisplatin also increased the likelihood of colostomy procedures.
Commonly, the first treatment therapy for anal canal cancer is chemoradiation. Radiation treatment combined with the anti-cancer drugs fluorouracil and mitomycin has a 5-year disease-free survival rate of about 65%. In recent studies, researchers have proposed that an effective treatment for anal canal cancer could be achieved by shrinking that cancer in the primary tumor and in the lymph node(s) before chemotherapy. The hypothesis held that disease-free survival rates could be increased if the cancer could be down-staged or downsized before concurrent chemoradiation by administering chemotherapy with the anti-cancer drug cisplatin as a treatment before surgery or radiotherapy of a malignancy. In earlier studies with this therapy, researchers received promising results.
To compare therapy with fluorouracil plus mitomycin and radiotherapy against treatment with fluorouracil plus cisplatin and radiotherapy, Jaffer A. Ajani, M.D. (University of Texas M. D. Anderson Cancer Center, Houston) and colleagues conducted a randomized controlled trial with 682 anal canal cancer patients. Of the total, 644 patients were assessable, and the median follow-up time for patients was 2.51 years.
The researchers found that for patients in the mitomycin-based group, the 5-year disease-free survival rate was 60%; for patients in the cisplatin-based group, it was 54%. In addition, the 5-year overall survival rates were 75% and 70% for the mitomycin-based group the cisplatin-based group, respectively. Cancer-related deaths were more frequent in the cisplatin-based group (54 patients) than in the mitomycin-based group (28 patients).
Patients in the mitomycin-based treatment group had 5-year local-regional recurrence rates of 25% and distant metastasis rates (spreading of the disease to other regions of the body) of 15%. These rates were 33% and 19% for the cisplatin-based treatment group, respectively. It was also found that patients in the mitomycin-based group had more severe hematologic (blood) toxicity than the other group.
Significantly higher cumulative rates of colostomy (a surgery that redirects waste to exit from the wall of the abdomen by connecting part of the colon onto the abdomen wall) were found in patients receiving cisplatin (19% vs. 10%), and the authors maintain that cisplatin as primary therapy should be avoided in this patient population.
“The question remains how to further improve disease-free and colostomy-free survival relative to the continued standard of concurrent chemoradiation with fluorouracil and mitomycin. Options to explore include targeted agents (e.g., results with concurrent cetuximab plus radiation for head/neck cancer), dose escalation with intensity-modulated radiation plus concurrent chemotherapy, and surgical excision of residual cancer after concurrent chemoradiation at an earlier interval, when sphincter preservation may still be feasible in select patients,” conclude the authors.
Fluorouracil, Mitomycin, and Radiotherapy vs Fluorouracil, Cisplatin, and Radiotherapy for Carcinoma of the Anal Canal
Jaffer A. Ajani, MD; Kathryn A. Winter, MS; Leonard L. Gunderson, MD; John Pedersen, MD; Al B. Benson III, MD; Charles R. Thomas Jr, MD; Robert J. Mayer, MD; Michael G. Haddock, MD; Tyvin A. Rich, MD; Christopher Willett, MD
JAMA. 2008;299(16):1914-1921.
Written by: Peter M Crosta