TY - JOUR
T1 - A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer
T2 - QUATTRO Study
AU - Oki, Eiji
AU - Kato, Takeshi
AU - Bando, Hideaki
AU - Yoshino, Takayuki
AU - Muro, Kei
AU - Taniguchi, Hiroya
AU - Kagawa, Yoshinori
AU - Yamazaki, Kentaro
AU - Yamaguchi, Tatsuro
AU - Tsuji, Akihito
AU - Iwamoto, Shigeyoshi
AU - Nakayama, Goro
AU - Emi, Yasunori
AU - Touyama, Tetsuo
AU - Nakamura, Masato
AU - Kotaka, Masahito
AU - Sakisaka, Hideki
AU - Yamanaka, Takeharu
AU - Kanazawa, Akiyoshi
N1 - Funding Information:
This study was supported by funding from Chugai Pharmaceutical Co, Ltd. The medical writing and editorial support for this article was also supported by funding from Chugai Pharmaceutical Co, Ltd. E. Oki has received honoraria for lecturing from Bayer, Chugai Pharmaceutical, Eli Lilly, Johnson & Johnson, Merck Serono, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha. T. Kato has received honoraria for lecturing from Bayer, Chugai Pharmaceutical, Eli Lilly, Yakult Honsha, and Takeda Pharmaceutical. K. Muro has received research funding from Daiichi Sankyo, Gilead Sciences, Kyowa Hakko Kirin, MSD, and Shionogi; and honoraria for lecturing from Chugai Pharmaceutical, Eli Lilly, Merck Serono, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha. K. Yamazaki has received honoraria for lecturing and research funding from Bristol-Myers Squibb; honoraria for lecturing from Bayer, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Merck Serono, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha; and research funding from Sanofi Aventis. A. Tsuji has received honoraria for lecturing and speaker’s bureau from Chugai Pharmaceutical, Taiho Pharmaceutical, and Takeda Pharmaceutical; and honoraria for lecturing from Bristol-Myers Squibb, Daiichi Sankyo, and Merck Serono. Y. Emi has received honoraria for lecturing from Chugai Pharmaceutical. M. Kotaka has received honoraria for lecturing from Chugai Pharmaceutical. T. Yamanaka has received honoraria for lecturing from Boehringer-Ingelheim, Chugai Pharmaceutical, Merck Serono, Taiho Pharmaceutical, and Takeda Pharmaceutical. All remaining authors have declared no conflicts of interest.
Publisher Copyright:
© 2018 The Authors
PY - 2018/6
Y1 - 2018/6
N2 - FOLFOXIRI plus bevacizumab is an effective for Asian metastatic colorectal cancer patients and the safety profile is manageable by adopting appropriate measures, even if severe neutropenia and febrile neutropenia develop at a higher frequency in ethnic Asian patients with UGT1A1*6 and *28 polymorphism. Background: FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet. Patients and Methods: This study was an open-label, single-arm, multi-centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab. The primary endpoint was the PFS rate at 10 months. Secondary endpoints included overall survival, response rate, and safety. Results: A total of 69 patients received FOLFOXIRI plus bevacizumab as induction therapy and were assessed for efficacy and safety. The PFS rate at 10 months was 75.2% and the median PFS was 13.3 months. Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively. Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%). Significantly more patients with grade 4 neutropenia had single-heterozygous UGT1A1*1/*6 or *1/*28 (46.2%) than UGT1A1 wild-type genotype (*1/*1) (13.3%) (P =.004). Conclusions: FOLFOXIRI plus bevacizumab is considered an effective first-line regimen that improves the outcome of patients with mCRC regardless of ethnicity. In Asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of UGT1A1*6 and *28 polymorphism, when FOLFOXIRI plus bevacizumab is administered.
AB - FOLFOXIRI plus bevacizumab is an effective for Asian metastatic colorectal cancer patients and the safety profile is manageable by adopting appropriate measures, even if severe neutropenia and febrile neutropenia develop at a higher frequency in ethnic Asian patients with UGT1A1*6 and *28 polymorphism. Background: FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet. Patients and Methods: This study was an open-label, single-arm, multi-centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab. The primary endpoint was the PFS rate at 10 months. Secondary endpoints included overall survival, response rate, and safety. Results: A total of 69 patients received FOLFOXIRI plus bevacizumab as induction therapy and were assessed for efficacy and safety. The PFS rate at 10 months was 75.2% and the median PFS was 13.3 months. Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively. Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%). Significantly more patients with grade 4 neutropenia had single-heterozygous UGT1A1*1/*6 or *1/*28 (46.2%) than UGT1A1 wild-type genotype (*1/*1) (13.3%) (P =.004). Conclusions: FOLFOXIRI plus bevacizumab is considered an effective first-line regimen that improves the outcome of patients with mCRC regardless of ethnicity. In Asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of UGT1A1*6 and *28 polymorphism, when FOLFOXIRI plus bevacizumab is administered.
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U2 - 10.1016/j.clcc.2018.01.011
DO - 10.1016/j.clcc.2018.01.011
M3 - Article
C2 - 29530335
AN - SCOPUS:85043333060
VL - 17
SP - 147
EP - 155
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
SN - 1533-0028
IS - 2
ER -