High-dose radiation therapy and neoadjuvant plus concomitant chemotherapy with 5-fluorouracil and cisplatin in patients with locally advanced squamous-cell anal canal cancer: Final results of a phase II study

Purpose: to analyse toxicity and response to a new scheme of neoadjuvant ch emotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advan ced anal canal squamous-cell carcinoma (ACC). Patients and methods: Eighty patients with an ACC > 40 mm and/or with lymph node involvement were included (1 T-1, 52 T-2, 14 T-3, 13 T-4, 18 N-0, 30 N-1, 32 N-2-N-3). Two cycles of 5-fluorouracil (5-FU) and CDDP were deliver ed as neoadjuvant CT and two during RT-CT. Pelvic (+/- inguinal) RT deliver ed 45 Gy in 25 fractions of 1.8 Gy. Involved fields were boosted after a on e to two month gap (15-20 Gy). The median follow-up was 29 months. Results: One patient died of a pulmonary embolism on day 4. All patients re ceived the entire treatment, with reduced 5-FU doses in 27% of the cases be cause of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities wer e observed. No toxic death occurred. Complete response (CR) and partial response (PR) rates were, respectively, 10% and 51% after neoadjuvant CT, 67% and 28% after RT-CT and 93% and 5% af ter treatment completion (including 4 abdomino-perineal resections). The three-year actuarial overall, tumour-specific, colostomy-free, relapse- free, disease-free and event-free survivals were 86%, 88%, 73%, 70%, 67% an d 63%, respectively. Conclusions: Tolerance was good. After neoadjuvant CT, most of the patients were objective responders. After treatment completion, all but five achiev ed CR. The long-term results confirm the durability of local control and lo w toxicity on the sphincter. An ongoing phase III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a high-dose boost irradia tion, on local control and colostomy-free survival.