Faculty Collaboration Database

Multicenter, randomized phase II trial of bevacizumab plus folinic acid, fluorouracil, gemcitabine (FFG) versus bevacizumab plus folinic acid, fluorouracil, oxaliplatin (FOLFOX4) as first-line therapy for patients with advanced colorectal cancer. Invest New Drugs 2012 Apr;30(2):772-8

Date

12/02/2010

Pubmed ID

21120580

DOI

10.1007/s10637-010-9598-9

Scopus ID

2-s2.0-84862274484 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

PURPOSE: To assess safety and efficacy of folinic acid, 5-fluorouracil, gemcitabine (FFG) and folinic acid, fluorouracil, oxaliplatin (FOLFOX4) regimens with added bevacizumab as first-line treatment in patients with advanced colorectal cancer (CRC).

PATIENTS AND METHODS: Patients with Stage III unresectable or Stage IV adenocarcinoma of the colon or rectum were randomly assigned to either FFG weekly for 6 weeks of an 8-week cycle or FOLFOX4 every 2 weeks. After FDA approval, bevacizumab 5 mg/kg was added every 2 weeks. Treatment continued until disease progression. Planned enrollment was 190 patients. Primary endpoint was overall response rate (ORR); secondary endpoints included evaluation of adverse events, time to progression (TTP), and overall survival (OS). Disease Control Rate (DCR; % of patients with complete or partial responses or stable disease) was a post hoc analysis.

RESULTS: The trial was stopped prematurely due to low enrollment. Of 84 enrolled patients (42 to each arm), 36 patients (18 in each arm) received bevacizumab. ORR was greater (P = .002) for FOLFOX4 (17/42; 40.5%) than for FFG (4/42; 9.5%); however, TTP, OS, and DCR results were not statistically different comparing FOLFOX4 and FFG. Peripheral neuropathy was more frequent (P = <.001) with FOLFOX4 (18/42; 42.9%) than with FFG (1/42; 2.4%).

CONCLUSIONS: FFG and FOLFOX4 were generally well tolerated. Based on ORR, FOLFOX4 was superior to FFG. However, differences in TTP and OS comparing regimens were inconclusive. General use of gemcitabine as a biomodulator of 5-fluorouracil in CRC cannot be recommended at this time and the regimen remains investigational.

Author List

Madajewicz S, Waterhouse DM, Ritch PS, Khan MQ, Higby DJ, Leichman CG, Malik SK, Hentschel P, Gill JF, Zhao L, Nicol SJ

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Colorectal Neoplasms
Deoxycytidine
Disease Progression
Drug Administration Schedule
Fluorouracil
Humans
Infusions, Intravenous
Kaplan-Meier Estimate
Leucovorin
Neoplasm Staging
Organoplatinum Compounds
Time Factors
Treatment Outcome
United States