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 ofneoadjuvant 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/orwith lymph node involvement were included (1 T₁, 52 T₂,14 T₃, 13 T₄, 18 N₀, 30 N₁, 32N₂–N₃). Two cycles of 5-fluorouracil (5-FU) andCDDP were delivered as neoadjuvant CT and two during RT–CT. Pelvic(± inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involvedfields were boosted after a one to two month gap (15–20 Gy). The medianfollow-up was 29 months.Results:One patient died of a pulmonary embolism on day 4. Allpatients 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 4toxicities 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 thepatients were objective responders. After treatment completion, all but fiveachieved CR. The long-term results confirm the durability of local control andlow toxicity on the sphincter. An ongoing phase III intergroup trial analysesthe impact of neoadjuvant CT, and the benefit of a high-dose boostirradiation, on local control and colostomy-free survival.