INITIAL RESULTS OF A PHASE-II TRIAL OF HIGH-DOSE RADIATION-THERAPY, 5-FLUOROURACIL, AND CISPLATIN FOR PATIENTS WITH ANAL CANCER (E4292) - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY

Purpose: A prospective clinical trial was performed to assess the resp onse and toxicity associated with the use of high dose radiation thera py, S-fluorouracil, and cisplatin in patients with anal cancer. Method s and Materials: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy i n 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m(2) per day intra venously, was given for the first 4 days of radiation therapy, and cis platin, 75 mg/m(2) intravenously, was given on day 1 of radiation ther apy. A second coarse of 5-fluorouracil and cisplatin was given after 3 6 Gy of radiation, when the radiation therapy was resumed. Results: Ni neteen patients entered this study and received treatment. Thirteen (6 8%) had a complete response, 5 (26%) had a partial response, and 1 (5% ) had stable disease. The patient with stable disease and one of the p atients with a partial response had complete disappearance of tumor mo re than 8 weeks after completion of radiation therapy. Fifteen patient s had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which wa s a complication of antibiotic therapy for a urinary tract infection. Conclusion: Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Pha se III clinical trial is planned in which radiation therapy, cisplatin , and 5-fluorouracil will be used as an experimental arm.