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.
OBJECTIVE
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).


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.
Montefiore North Division Cancer Center, 600 E 233rd Street, Bronx, NY 10466, USA. stefanmadajewicz@yahoo.com
Stefan
S
Madajewicz
David M
DM
Waterhouse
Paul S
PS
Ritch
M Qaseem
MQ
Khan
Donald J
DJ
Higby
Cynthia G
CG
Leichman
Sandeep K
SK
Malik
Patricia
P
Hentschel
John F
JF
Gill
Luping
L
Zhao
Steven J
SJ
Nicol
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil