Preliminary results of a phase II study of high-dose radiation therapy and neoadjuvant plus concomitant 5-fluorouracil with CDDP chemotherapy for patients with anal canal cancer: A French cooperative study

Background. Chemotherapy (5-fluorouracil-milomycin C) concomitant with radiotherapy (RT) increases local control and colostomy-free survival in advanced anal canal carcinomas (ACC). The purpose of this prospective trial was to analyse the toxicity of and response to an induction chemotherapy combining 5-fluorouracil (5-FU) and CDDP administered concomitantly with irradiation. Patients and methods. Thirty patients (24 F/6 M, mean age 60, range 38-74) with an advanced ACC > 40 mm and/or with node involvement were prospectively treated(1 T1, 16 T2, 8 T3, 5 T4, 10 N1, 1 N2, 8 N3) from November 1994 to January 1996. Two induction and two concomitant cycles of 5-FU (800 mg/ m(2) D1-4 infusion) and CDDP (80 mg/i.v./m(2) at D1) were delivered. RT consisted of 45 Gy (1.8 Gy/fr, 5 fr/w) on pelvis +/- inguinal nodes or 30 Gy (3 Gy/fr, 4 fr/w) by direct perineal field. A roost (15-20 Gy) was delivered six weeks later. Results. Toxicity one patient died of a pulmonary embolism on D4. The remaining 29 received the entire treatment, with reduced 5-FU doses in 11 patients because of acute toxicity. The RT boost was delayed for one patient (aplasia). In 109 cycles, 3 grade 4 and 17 grade 3 toxicities were observed, there were no toxic deaths, Tumor response: the complete response (CR) and partial response (PR) rates were, respectively: 11% and 61% after induction chemotherapy, 59% and 31% after concomitant radiochemotherapy and 96% and 0% two months after completion of the treatment. No tumor progression was observed. Conclusion, the treatment was well tolerated and there was good compliance. After induction chemotherapy, most of the patients were in PR, with some even in CR. After completion of the treatment all but one were in CR. The tumor response and the long term results of 50 patients will be analysed before initiation of a randomised trial is considered.