Toshihiro Kudo1,2, Ichiro Takemasa3, Tsuyoshi Hata4, Daisuke Sakai5, Hidekazu Takahashi4, Naotsugu Haraguchi4, Junichi Nishimura4, Taishi Hata4, Chu Matsuda4, Taroh Satoh5, Tsunekazu Mizushima6, Masaki Mori7, Yuichiro Doki4. 1. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan, tkudo@mc.pref.osaka.jp. 2. Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan, tkudo@mc.pref.osaka.jp. 3. Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan. 4. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. 5. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan. 6. Department of Therapeutics for Inflammatory Bowel Diseases, Graduate School of Medicine, Osaka University, Osaka, Japan. 7. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract
OBJECTIVES: The aim of this study was to determine the recommended dose (RD) of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as a neoadjuvant chemotherapy in patients with locally advanced rectal cancer. METHOD: Patients received irinotecan and oxaliplatin (85 mg/m2) on day 1, and capecitabine (1,000 mg/m2 orally twice daily) on days 1-7 of a biweekly schedule. Three dose levels, ranging from 100 to 150 mg/m2, were explored for irinotecan in sequential cohorts of 6 patients. Dose-limiting toxicities (DLTs) were assessed in the first cycle to determine the RD. RESULTS: Six patients were enrolled. The DLT was grade 3 febrile neutropenia, which was observed in 2 of the 6 patients at dose level 1. The RD of irinotecan was defined as 150 mg/m2. Toxicity was manageable: the most common grade ≥3 toxicities were neutropenia (2 patients), anemia (1 patient), and anorexia (1 patient). Nodal downstaging (cN+ to ypN0) was detected in 2 patients and the T stage was downstaged in 3 patients. CONCLUSIONS: XELOXIRI is a feasible and active regimen for patients with locally advanced rectal cancer. Febrile neutropenia was the DLT, and the RD of irinotecan is 150 mg/m2.
OBJECTIVES: The aim of this study was to determine the recommended dose (RD) of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as a neoadjuvant chemotherapy in patients with locally advanced rectal cancer. METHOD:Patients received irinotecan and oxaliplatin (85 mg/m2) on day 1, and capecitabine (1,000 mg/m2 orally twice daily) on days 1-7 of a biweekly schedule. Three dose levels, ranging from 100 to 150 mg/m2, were explored for irinotecan in sequential cohorts of 6 patients. Dose-limiting toxicities (DLTs) were assessed in the first cycle to determine the RD. RESULTS: Six patients were enrolled. The DLT was grade 3 febrile neutropenia, which was observed in 2 of the 6 patients at dose level 1. The RD of irinotecan was defined as 150 mg/m2. Toxicity was manageable: the most common grade ≥3 toxicities were neutropenia (2 patients), anemia (1 patient), and anorexia (1 patient). Nodal downstaging (cN+ to ypN0) was detected in 2 patients and the T stage was downstaged in 3 patients. CONCLUSIONS:XELOXIRI is a feasible and active regimen for patients with locally advanced rectal cancer. Febrile neutropenia was the DLT, and the RD of irinotecan is 150 mg/m2.