Mitomycin C with continuous fluorouracil or with cisplatin in combination with radiotherapy for locally advanced anal cancer (European Organisation for Research and Treatment of Cancer phase II study 22011-40014)

Purpose: To assess the feasibility and activity of radio-chemotherapy with mitomycin C (MMC) and cisplatin (CDDP) in locally advanced squamous cell anal carcinoma with reference to radiotherapy (RT) combined with MMC and fluorouracil (5-FU). Patients and methods: Patients with measurable disease >4 cm NO or N+ received RT (36 Gy + 2 week gap + 23.4 Gy) with either MMC/CDDP or MMC/5-FU (MMC 10 mg/m(2) d1 of each sequence; 5-FU 200 mg/m(2)/day c.i.v. daily; CDDP 25 mg/m(2) weekly). Forty patients/arm were needed to exclude a RECIST objective response rate (ORR), 8 weeks after treatment, of <75% (Fleming 1, alpha = 10%, beta = 10%). Results: The ORR was 79.5% (31/39) (lower bound confidence interval [CI]: 68.8%) with MMC/5-FU versus 91.9% (34/37) (lower bound CI: 82.8%) with MMC/CDDP. In the MMC/5-FU group, two patients (5.1%) discontinued treatment due to toxicity versus 11 (29.7%) in the MMC/CDDP group. Nine grade 3 haematological events occurred with MMC/CDDP versus none with 5-FU/MMC. The rate of other toxicities did not differ. There was no toxic death. Thirty-one patients in the MMC/5-FU arm (79.5%) and 18 in the MMC/CDDP arm (48.6%) were fully compliant with the protocol treatment (p = 0.005). Conclusions: Radio-chemotherapy with MMC/CDDP seems promising as only MMC/CDDP demonstrated enough activity (RECIST ORR >75%) to be tested further in phase III trials; MMC/5-FU did not. MMC/CDDP also had an overall acceptable toxicity profile. (C) 2009 Elsevier Ltd. All rights reserved.