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A Phase I Study of Infusional 5-Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan in Japanese Patients with Advanced Colorectal Cancer Who Harbor UGT1A1*1/*1,*1/*6 or *1/*28Sunakawa Y.a · Fujita K.a, b · Ichikawa W.a, c · Ishida H.a · Yamashita K.a · Araki K.a · Miwa K.a · Kawara K.a · Akiyama Y.a, b · Yamamoto W.a · Nagashima F.a · Saji S.a · Sasaki Y.a, b
aDepartment of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University, bProject Research Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, and cDepartment of Clinical Oncology, National Defense Medical College, Tokorozawa, Japan
Objective: To evaluate the safety and efficacy of combination chemotherapy with 5-fluorouracil (5-FU), leucovorin, irinotecan and oxaliplatin (FOLFOXIRI) in Japanese patients with advanced colorectal cancer. Methods: This phase I dose-finding study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD) or both of FOLFOXIRI. Patients with UDP-glucuronosyltransferase (UGT) 1A1*6/*6, *28/*28 and *6/*28 genotypes were excluded, because these UGT1A1 genotypes are linked to severe neutropenia in Japanese. Results: A total of 10 Japanese patients with advanced colorectal cancer were studied. The MTD of FOLFOXIRI in these Japanese patients was 165 mg/m2 irinotecan, 85 mg/m2 oxaliplatin and 2,400 mg/m2 5-FU. Accordingly, the RD of FOLFOXIRI was determined to be 150 mg/m2 irinotecan, 85 mg/m2 oxaliplatin and 2,400 mg/m2 5-FU. Toxic effects, evaluated until the completion of 4 cycles, were manageable. Grade 3–4 neutropenia occurred in 27% of cycles, but there was no febrile neutropenia. Among the 9 assessable patients, the objective response rate was 89%. Conclusions: We thus determined the RD of FOLFOXIRI in Japanese patients with advanced colorectal cancer who do not have UGT1A1*28/*28, *6/*6 or *6/*28 genotypes. Our results indicate that FOLFOXIRI is a well-tolerated regimen for these Japanese patients.
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