The aim of this single-arm phase II clinical trial was to evaluate whether the alternate-day administration of S-1 plus irinotecan would reduce the incidence of severe diarrhea in comparison to consecutive-day S-1 administration (standard IRIS regimen) in second-line treatment in patients with metastatic colorectal cancer.
Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatin and fluoropyrimidine were enrolled. Irinotecan (150 mg/m2) and bevacizumab (5mg/kg) were given intravenously on day 1. Oral S-1 was administered on alternate-days at a dose of 40-60mg twice a day. Cycles were repeated every two weeks. The primary endpoint was the incidence of grade ≥3 diarrhea. Our hypothesis set the 21% as a threshold incidence and 10% as an expected incidence from previous studies with one-sided alpha = 0.05. The secondary endpoints included the relative dose intensity, progression free survival, overall survival and other adverse events.
A total of 51 patients were enrolled. The incidence of grade ≥3 diarrhea was 15.7% (8/51). Other common grade ≥3 adverse events were neutropenia, anemia, thrombocytopenia and fatigue were 13.7% (7/51), 5.9% (3/51), 2.0% (1/51) and 5.9% (3/51), respectively. The relative dose intensities of irinotecan, bevacizumab, and S-1 were 80.0%, 86.8%, and 77.7%, respectively. The median progression free survival and overall survival were 8.4 months (5.8 - 9.8) and 17.1 months (11.8 - 22.3).
The alternate day S-1 administration doesn’t have significant effectiveness to reduce diarrhea in patients who received second line treatment for metastatic colorectal cancer.
Clinical trial identification
Legal entity responsible for the study
Epidemiological and Clinical research Information Network (ECRIN).
Taiho Pharmaceutical Co., Ltd.
All authors have declared no conflicts of interest.