5-Fluorouracil Versus Capecitabine as Perioperative Treatment for Locally Advanced Rectal Cancer. a Randomized Phase III Trial
5-Fluorouracil (5-FU) based chemoradiotherapy (CRT) is regarded a standard perioperative
treatment in locally advanced rectal cancer (LARC). We investigate the replacement of 5-FU
by the oral pro-drug capecitabine (cape) within a randomized phase III trial. Patients aged
≥18 years with LARC stage II or III are recruited into this two-arm, two-cohort randomized
non-inferiority phase-III trial (arm A: cape, arm B: 5-FU; cohort [C] I: adjuvant, C II:
neoadjuvant). Regimens: Arm A: CRT: 50.4 Gy + cape 1,650 mg/m² days 1-38 plus five cycles of
cape 2,500 mg/m² d 1-14, repeated d 22 (C I: 2 x cape, CRT, 3 x cape; C II: CRT, TME surgery
followed by cape x 5). Arm B: CRT: 50.4 Gy + infusional 5-FU 225 mg/m² daily [C I] or
infusional 5-FU 1,000 mg/m² d 1-5 and 29-33 [C II] plus 4 cycles of bolus 5-FU 500mg/m² d
1-5, repeated d 29 (C I: 2 x 5-FU, CRT, 2 x 5-FU; C II: CRT, TME surgery followed by 5-FU x
4). Primary endpoint is 5-year overall survival (OS), secondary endpoints comprise 3-year
disease-free survival (DFS) and safety.
The study is designed to investigate whether 5- year overall survival rate (SR5) is
non-inferior in arm A versus arm B. We hypothesize that SR5 in the standard arm B is 57.5%.
Sample size calculation is performed with a power of 80% and a type I error of 5% and with a
drop-out rate of 5%. Therefore, a total of at least 372 evaluable patients (i.e. 186 per
arm) is required to confirm non-inferiority of the experimental arm A with a non-inferiority
margin of maximal 12.5% and a median follow-up time of 48 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Ralf Hofheinz, MD
Universitätsmedizin Mannheim Germany, University of Heidelberg
Germany: Ethics Commission