A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study

Eiji Oki, Takeshi Kato, Hideaki Bando, Takayuki Yoshino, Kei Muro, Hiroya Taniguchi, Yoshinori Kagawa, Kentaro Yamazaki, Tatsuro Yamaguchi, Akihito Tsuji, Shigeyoshi Iwamoto, Goro Nakayama, Yasunori Emi, Tetsuo Touyama, Masato Nakamura, Masahito Kotaka, Hideki Sakisaka, Takeharu Yamanaka, Akiyoshi Kanazawa

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)147-155
ページ数9
ジャーナルClinical Colorectal Cancer
17
発行部数2
DOI
出版物ステータス出版済み - 6 2018

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irinotecan
oxaliplatin
Fluorouracil
Colorectal Neoplasms
Neutropenia
Febrile Neutropenia
Disease-Free Survival
Therapeutics
Survival Rate
Safety
Bevacizumab
Phase II Clinical Trials

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology

これを引用

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer : QUATTRO Study. / Oki, Eiji; Kato, Takeshi; Bando, Hideaki; Yoshino, Takayuki; Muro, Kei; Taniguchi, Hiroya; Kagawa, Yoshinori; Yamazaki, Kentaro; Yamaguchi, Tatsuro; Tsuji, Akihito; Iwamoto, Shigeyoshi; Nakayama, Goro; Emi, Yasunori; Touyama, Tetsuo; Nakamura, Masato; Kotaka, Masahito; Sakisaka, Hideki; Yamanaka, Takeharu; Kanazawa, Akiyoshi.

:: Clinical Colorectal Cancer, 巻 17, 番号 2, 06.2018, p. 147-155.

研究成果: ジャーナルへの寄稿記事

Oki, E, Kato, T, Bando, H, Yoshino, T, Muro, K, Taniguchi, H, Kagawa, Y, Yamazaki, K, Yamaguchi, T, Tsuji, A, Iwamoto, S, Nakayama, G, Emi, Y, Touyama, T, Nakamura, M, Kotaka, M, Sakisaka, H, Yamanaka, T & Kanazawa, A 2018, 'A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study', Clinical Colorectal Cancer, 巻. 17, 番号 2, pp. 147-155. https://doi.org/10.1016/j.clcc.2018.01.011
Oki, Eiji ; Kato, Takeshi ; Bando, Hideaki ; Yoshino, Takayuki ; Muro, Kei ; Taniguchi, Hiroya ; Kagawa, Yoshinori ; Yamazaki, Kentaro ; Yamaguchi, Tatsuro ; Tsuji, Akihito ; Iwamoto, Shigeyoshi ; Nakayama, Goro ; Emi, Yasunori ; Touyama, Tetsuo ; Nakamura, Masato ; Kotaka, Masahito ; Sakisaka, Hideki ; Yamanaka, Takeharu ; Kanazawa, Akiyoshi. / A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer : QUATTRO Study. :: Clinical Colorectal Cancer. 2018 ; 巻 17, 番号 2. pp. 147-155.
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title = "A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study",
abstract = "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.",
author = "Eiji Oki and Takeshi Kato and Hideaki Bando and Takayuki Yoshino and Kei Muro and Hiroya Taniguchi and Yoshinori Kagawa and Kentaro Yamazaki and Tatsuro Yamaguchi and Akihito Tsuji and Shigeyoshi Iwamoto and Goro Nakayama and Yasunori Emi and Tetsuo Touyama and Masato Nakamura and Masahito Kotaka and Hideki Sakisaka and Takeharu Yamanaka and Akiyoshi Kanazawa",
year = "2018",
month = "6",
doi = "10.1016/j.clcc.2018.01.011",
language = "English",
volume = "17",
pages = "147--155",
journal = "Clinical Colorectal Cancer",
issn = "1533-0028",
publisher = "Elsevier",
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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

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

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JO - Clinical Colorectal Cancer

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