Three cytotoxic drugs combined with pelvic radiation and as maintenance chemotherapy for patients with squamous cell carcinoma of the anus (SCCA): Long-term follow-up of a phase II pilot study using 5-fluorouracil, mitomycin C and cisplatin

PurposePhase III trials in the 1990s for squamous cell carcinoma of the anus (SCCA) demonstrated 5-fluorouracil (5FU) and mitomycinC (MMC) chemoradiation (CRT) improved outcome compared to radiation (RT) alone, but local recurrence remained significant. This prospective pilot study intensified treatment by integrating 3 cytotoxic drugs into CRT and maintenance chemotherapy.MethodsCRT comprised 5-FU 1000 mg/m2 days1–4,29–32, MMC 10 mg/m2 day1 and Cisplatin (CDDP) 60 mg/m2 days1 and 29, with 45 Gy in 25 daily fractions, followed by a 15 Gy boost. Maintenance chemotherapy started 4–8 weeks later, three courses repeated every 21 days, using 5-FU/CDDP doses above, with MMC reduced to 7 mg/m2 and administered with the first and third cycles.ResultsIn CRT only 14/19 (74%) patients received protocol-defined chemotherapy doses in week 5. Compliance to maintenance chemotherapy was poor. 15/19 started cycle 1, 13 started cycle 2 and 11 cycle 3. 17/19 experienced G3–G5 toxicity (16 Grade 3/4 and one Grade 5). 16/19 patients (84%) remain alive and disease-free – median follow-up 79 months (34–115).ConclusionsDespite favourable results, the significant toxicity and low compliance of the three-drug CRT regimen used, deemed it unsuitable for testing in a phase III trial. A two-drug maintenance regimen was explored in the ACT II trial.