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

Purpose: to analyse toxicity and response to a new scheme of neoadjuvant chemotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advanced 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 T₁, 52 T₂, 14T₃, 13 T₄, 18 N₀, 30 N₁, 32 N₂-N₃). Two cycles of 5-fluorouracil (5-FU) and CDDP were delivered as neoadjuvant CT and two during RT-CT. Pelvic (± inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involved fields were boosted after a one 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 received the entire treatment, with reduced 5-FU doses in 27% of the cases because of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities were 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% after 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% and 63%, respectively. Conclusions: Tolerance was good. After neoadjuvant CT, most of the patients were objective responders. After treatment completion, all but five achieved CR. The long-term results confirm the durability of local control and low toxicity on the sphincter. An ongoing phase III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a high-dose boost irradiation, on local control and colostomy-free survival.