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

Abstract

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.

• Authors: 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
• Journal: Clinical colorectal cancer (Clin Colorectal Cancer) Vol. 17 Issue 2 Pg. 147-155 (06 2018) ISSN: 1938-0674 [Electronic] United States
• PMID: 29530335 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Organoplatinum Compounds
• Bevacizumab
• UGT1A1 enzyme
• Glucuronosyltransferase
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adenocarcinoma (drug therapy, genetics, mortality)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Asian People
• Bevacizumab (administration & dosage, adverse effects)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Chemotherapy-Induced Febrile Neutropenia (epidemiology, genetics)
• Colorectal Neoplasms (drug therapy, genetics, mortality)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Glucuronosyltransferase (genetics)
• Humans
• Induction Chemotherapy (methods)
• Kaplan-Meier Estimate
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Progression-Free Survival