Chu Matsuda1, Michitaka Honda2, Chihiro Tanaka3, Ken Kondo4, Takao Takahashi5, Chihiro Kosugi6, Yukihiko Tokunaga7, Hiroyoshi Takemoto8, Ho Min Kim9, Junichi Sakamoto10, Koji Oba11, Hideyuki Mishima12. 1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. 2. Department of Disaster and Comprehensive Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan. mhonda@fukushimamed.com. 3. Gifu Prefectural General Medical Center, Gifu, Japan. 4. Nagoya Medical Center, Nagoya, Japan. 5. Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan. 6. Teikyo University Chiba Medical Center, Chiba, Japan. 7. Kyoto Japan Post Hospital, Kyoto, Japan. 8. Department of Surgery, Kinki Central Hospital, Osaka, Japan. 9. Department of Surgery, Rinku General Medical Center, Izumisano, Japan. 10. Tokai Central Hospital, Kagamigahara, Japan. 11. Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan. 12. Cancer Center, Aichi Medical University, Aichi, Japan.
Abstract
BACKGROUND: 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 for patients with metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatin and fluoropyrimidine were enrolled. Irinotecan (150 mg/m2) and bevacizumab (5 mg/kg) were given intravenously on day 1. Oral S-1 was administered on alternate days at a dose of 40-60 mg twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the incidence of grade ≥ 3 diarrhea. Our hypothesis set 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. RESULTS: 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). CONCLUSIONS: The alternate-day S-1 administration does not have significant effectiveness to reduce diarrhea in patients who received second-line treatment for metastatic colorectal cancer.
BACKGROUND: 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 for patients with metastatic colorectal cancer. METHODS:Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatin and fluoropyrimidine were enrolled. Irinotecan (150 mg/m2) and bevacizumab (5 mg/kg) were given intravenously on day 1. Oral S-1 was administered on alternate days at a dose of 40-60 mg twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the incidence of grade ≥ 3 diarrhea. Our hypothesis set 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. RESULTS: 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). CONCLUSIONS: The alternate-day S-1 administration does not have significant effectiveness to reduce diarrhea in patients who received second-line treatment for metastatic colorectal cancer.