PRIMARY CHEMORADIATION THERAPY WITH FLUOROURACIL AND CISPLATIN FOR CANCER OF THE ANUS - RESULTS IN 35 CONSECUTIVE PATIENTS

Purpose: This prospective phase II study was design to test the activi ty and toxicity of a regimen of (5-FU) and cisplatin (CDDP) in combina tion with radiation therapy in the treatment of epidermoid cancer of t he anal canal. Patients and Methods: Thirty-five consecutive patients with untreated epidermoid cancer of the anal canal were candidates for chemoradiation therapy (CRT). Staging of cancer was as follows: T1, 2 6%; T2, 60%; T3, 14%; and N1,2,3, 26%. No patient had distant metastas es. The treatment protocol consisted of two to three cycles of chemoth erapy starting on days 1 and 21 and concurrent radiotherapy at a daily dose of 1.8 Gy up to a total dose of 36 to 38 Gy in 4 weeks, delivere d to the anal region, perineum, middle and lower pelvis, and inguinal and external iliac nodes. Radiotherapy was then delivered to the anope rineal region and metastatic inguinal nodes to a total dose of 18 to 2 4 Gy in 10 fractions. Chemotherapy consisted of 24-hour intravenous (I V) infusion of 5FU 750 mg/m2 on days 1 to 4 and CDDP 100 mg/m2 by 60-m inute IV infusion on day 1. Results: All patients received two cycles of chemotherapy; the second was delayed in three patients because of l eukopenia that was evident in 11 (31%). In eight patients, a third cyc le was added. They all experienced nausea or vomiting; one patient sho wed signs of cardiotoxicity and one developed proctitis, dermatitis, a nd diarrhea (grade 3). Complete regression (CR) was assessed in 33 pat ients (94%); nine patients with metastatic lymph nodes also had CR. Tw o patients had a partial response (PR); both underwent abdominoperinea l resection, which was not curative in one. Two patients (6%) had a lo cal recurrence; in one, this was associated with hepatic metastases. O ne of these patients underwent surgery and is alive after about 4 year s, while the other is undergoing chemotherapy. After a median follow-u p duration of 37 months, 94% of patients are alive without evidence of disease and 86% are colostomy-free. Conclusion: This regimen is well tolerated: its toxicity does not exceed that observed with the combina tion of 5-FU and mitomycin (MMC). Compared with our previous experienc e based on the classic CRT (5-FU, MMC, and radiation), the objective r esponse rate observed with this new combination was similar. However, the local recurrence rate, observed in patients treated with the new r egimen, was lower (6% v 24%). According to more recent data from the l iterature, primary CRT is the elective indication in epidermoid cancer of the anus and replacement of MMC with CDDP seems on effective and l ogical evolution. (C) 1996 by American Society of Clinical Oncology.