Induction Chemotherapy and Dose Intensification of the Radiation Boost in Locally Advanced Anal Canal Carcinoma: Final Analysis of the Randomized UNICANCER ACCORD 03 Trial

Purpose Concomitant radiochemotherapy (RCT) is the standard for locally advanced anal canal carcinoma (LAACC). Questions regarding the role of induction chemotherapy (ICT) and a higher radiation dose in LAACC are pending. Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival (CFS). Patients and Methods Patients with tumors 40 mm, or 40 mm and N1-3M0 were randomly assigned to one of four treatment arms: (A) two ICT cycles (fluorouracil 800 mg/m 2 /d intravenous [IV] infusion, days 1 through 4 and 29 to 32; and cisplatin 80 mg/m 2 IV, on days 1 and 29), RCT (45 Gy in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), and standard-dose boost (SD; 15 Gy); (B) two ICT cycles, RCT, and high-dose boost (HD; 20-25 Gy); (C): RCT and SD boost (reference arm); and (D) RCT and HD boost. Results Two hundred eighty-three of 307 patients achieved full treatment. With a median follow-up period of 50 months, the 5-year CFS rates were 69.6%, 82.4%, 77.1%, and 72.7% in arms A, B, C, and D, respectively. Considering the 2 2 factorial analysis, the 5-year CFS was 76.5% versus 75.0% (P .37) in groups A and B versus C and D, respectively (ICT effect), and 73.7% versus 77.8% in groups A and C versus B and D, respectively (RT-dose effect; P .067).