Capecitabine (Cape) versus 5-fluorouracil (5-FU)-based (neo-)adjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC): Safety results of a randomized, phase III trial

Abstract

4014 Background: 5-FU based CRT is regarded standard perioperative treatment in LARC. Here we report safety data of a non-inferiority phase III trial investigating (neo-)adjuvant CRT with Cape in comparison with 5-FU. Methods: Patients (pts) aged ≥18 years with LARC UICC stages II or III were recruited in this two-arm, two-strata randomized phase-III trial (arm A: Cape, arm B: 5-FU; stratum [S] I: adjuvant, S 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, rep. d 22 (S I: 2 x Cape, CRT, 3 x Cape; S II: CRT, TME surgery followed by Cape x 5). Arm B: CRT: 50.4 Gy + 5-FU 225 mg/m2 c.i. daily [S I] or 5-FU 1,000 mg/m2 c.i. d 1–5 and 29–33 [S II] plus 4 cycles of bolus 5-FU 500mg/m2 d 1–5, rep. d 29 (S I: 2 x 5-FU, CRT, 2 x 5-FU; S II: CRT, TME surgery followed by 5-FU x 4). Primary endpoint was survival, secondary endpoints comprised safety and disease-free survival. Results: Of 401 randomized pts a total of 392 are evaluable (Arm A n=197, arm B n=195; S I n=231, S II n=161). Both arms were well balanced with respect to age, sex, WHO status, T- and N- stages. Regarding duration of treatment, 78% (Cape) and 80% (5-FU) completed all scheduled treatment cycles in S I, and 46% (Cape) and 40% (5-FU) in neoadjuvant stratum S II. In S II a total of 38% (Cape) and 43% (5-FU) did not continue chemotherapy after tumour resection. Concerning early efficacy endpoints in S II, pts treated with Cape (evaluable thus far n=121) exhibited a higher rate of T-downstaging (defined as ypT0–2; 52 vs 39%; p=0.16) and N0 (71 vs 56%; p=0.09). Regarding overall safety (NCI-CTC), pts receiving Cape experienced significantly less leukopenia (25 vs 35%; p=0.04), but more hand-foot syndrome (31 vs. 2%; p<0.001). Stomatitis/mucositis, diarrhea, nausea/vomiting, and radiodermatitis were not significantly different between both arms. Conclusions: Given the observed safety profile and the trend in improved downstaging in neoadjuvant stratum, Cape exhibits a potential to replace 5-FU as perioperative treatment of LARC. Efficacy results on the primary endpoint are expected for 2010. [Table: see text]