A multicenter phase-II study of 5-FU, leucovorin and oxaliplatin (FOLFOX6) in patients with pretreated metastatic colorectal cancer.
OBJECTIVE
Infusional 5-fluorouracil and leucovorin with oxaliplatin is one of the standard regimens for patients with pretreated metastatic colorectal cancer, as well as for first-line chemotherapy. FOLFOX4 has shown its efficacy in pivotal trials, but patients must make twice-weekly hospital visits. FOLFOX6 is a more convenient regimen, requiring a visit once every two weeks. The objective of this study was to evaluate the efficacy and safety profile of FOLFOX6 in Japanese patients with pretreated colorectal cancer.


METHODS
Fifty-one metastatic colorectal cancer patients who failed to respond to first-line chemotherapy were enrolled in the study from April to July 2005. Oxaliplatin, 5-fluorouracil and l-leucovorin were administered every two weeks. Oxaliplatin (100 mg/m(2)) and l-leucovorin (200 mg/m(2)) were given intravenously over 2 h followed by 5-fluorouracil bolus 400 mg/m(2) i.v. and 46-h infusion of 2400 mg/m(2). The primary endpoint was the response rate.


RESULTS
Two patients had no measurable lesions and were excluded from the efficacy analysis. Of the 49 eligible patients, one complete response and 6 partial responses were observed, resulting in a response rate (RR) of 14.3% (95% confidence interval: 5.9-27.2%). Median time to treatment failure and progression-free survival was 4.4 and 5.3 months, respectively. Overall survival was 11.4 months. The incidence of grade 2/3 (Debiopharm neurotoxicity criteria) peripheral neuropathy was 41.2%, whereas the overall incidence of grade 3/4 neutropenia was 43.2%.


CONCLUSIONS
The results of our study suggest that FOLFOX6 had an acceptable profile in terms of both efficacy and safety in previously treated colorectal cancer patients.
Kato
Ken
K
Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan. kenkato@ncc.go.jp
Inaba
Yoshitaka
Y
Tsuji
Yasushi
Y
Esaki
Taito
T
Yoshioka
Akira
A
Mizunuma
Nobuyuki
N
Mizuno
Toshiro
T
Kusaba
Hitoshi
H
Fujii
Hirohumi
H
Muro
Kei
K
Shimada
Yasuhiro
Y
Shirao
Kuniaki
K
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011446:Prospective Studies; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil