Toxicity and efficacy of four schedules of intensified neoadjuvant chemoradiotherapy (RCT) with irinotecan and 5-Fu or Capecitabine in patients with locally advanced rectal cancer (LARC)

Abstract

13550 Background: After neoadjuvant RCT in patients with LARC the rate of complete response (pCR), nearly complete response (nCR)and also the ypN0 category influences survival. So four different schedules of neoadjuvant RCT with irinotecan and 5-Fu or Capecitabine were compared in efficacy (pCR, nCR, ypN0) but also in the main toxicity (diarrea III/IV CTC). Methods: Conventional radiation was given at daily fractions of 1.8Gy to a total dose of 50.4Gy and 5.4Gy boost in all schedules. In our first schedule 5-Fu (250mg/m2, d1–43) and irinotecan (40mg/m2, d1,8,15,22,29,36) (group A), in our next schedule capecitabine (1500mg/m2, d1–43) and irinotecan (40mg/m2, d1,8,15,22,29,36) (group B), and then next capecitabine (1500mg/m2, d1–14, 22–35) and irinotecan (50mg/m2, d1,8,22,29) (group C) and now capecitabine (1500mg/m2, d1–14, 22–35) and irinotecan (60mg/m2, d1,8,22,29) (group D) was applicated concurrently. Surgery was performed 4–6 weeks after RCT. Results: Group A-B-C-D: number of patients: 37 - 28 - 20 - up to now 11; clinical state UICC II/III: 6/31 - 2/28 - 5/15 - 1/10; diarrhea (III+IV): 12/37(32%) - 11/28(39%) - 2/20(10%) - 1/11(9%); pCR: 9/37(24%) - 4/26(15%) - 0/20(0%) -3 /9(33%); nCR: 10/37(27%) - 3/26(12%) - 5/20(25%) - 1/9(11%); ypNo: 25/37(68%) - 15/26(58%) - 12/20(60%) - 6/9(67%). Conclusions: Neoadjuvant RCT with 5-Fu or capecitabine in combination with irinotecan is high effective. The splitting of capecitabine with a break in the third week of radiation reduces toxicity but not efficacy. In our trials during RCT a total dose of 240mg/m2 irinotecan in combination with 5-Fu/capecitabine must be applicated to receive a high rate of pCR. No significant financial relationships to disclose.