A Phase I Study of Infusional 5-Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan in Japanese Patients with Advanced Colorectal Cancer Who Harbor <i>UGT1A1</i>*<i>1/</i>*<i>1</i>,*<i>1/</i>*<i>6</i> or *<i>1/</i>*<i>28</i>

<i>Objective:</i> 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. <i>Methods:</i> This phase I dose-finding study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD) or both of FOLFOXIRI. Patients with <i>UDP-glucuronosyltransferase (UGT) 1A1</i>*<i>6</i>/*<i>6</i>, *<i>28</i>/*<i>28</i> and *<i>6</i>/*<i>28</i> genotypes were excluded, because these <i>UGT1A1</i> genotypes are linked to severe neutropenia in Japanese. <i>Results:</i> 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%. <i>Conclusions:</i> We thus determined the RD of FOLFOXIRI in Japanese patients with advanced colorectal cancer who do not have <i>UGT1A1</i>*<i>28/</i>*<i>28</i>, *<i>6/</i>*<i>6</i> or *<i>6/</i>*<i>28</i> genotypes. Our results indicate that FOLFOXIRI is a well-tolerated regimen for these Japanese patients.