[Retrospective analysis of FOLFOX4 neurotoxicity for recovery from advanced colorectal cancer].
BACKGROUND
Oxaliplatin (L-OHP) in combination with infusional 5-fluorouracil/leucovorin (FOLFOX), has been established as a key drug for advanced colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. No prior recovery from neurotoxicity data is available for Japanese patients treated by FOLFOX4 for advanced colorectal cancer.


OBJECTIVE
We performed a retrospective study on the recovery from chronic neurotoxicity and period for discontinuing FOLFOX4 therapy due to neurotoxicity.


METHODS
One hundred eighty-seven patients with advanced or recurrent colorectal cancer were treated with FOLFOX4 regimen between April 2005 and March 2006. We evaluated chronic peripheral sensory neuropathy by National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0), and calculated the period of recovery from grade 3 and grade 2 neurotoxicity by the Kaplan-Meier method.


RESULTS
Seventy-two patients had to discontinue FOLFOX4 due to grade 3 and grade 2 neurotoxicity. grade 2 and grade 3 neurotoxicity was observed in 39 (20.8%) and 33 (17.6%) patients, respectively. Patients with grade 2 and grade 3 neurotoxicity had a median age of 59 years (range, 35-75 years), and 62 years (range, 36-73 years), respectively. The median number of courses until expression of grade 2 neurotoxicity was ten (range, 2-23 courses) and that for grade 3 neurotoxicity was also ten (range, 4-14 courses). The period of reducing grade 2 neurotoxicity to grade 1 was 56 days, while that for reducing grade 3 neurotoxicity to grade 1 was 106 days. FOLFOX4 was reintroduced in 15 patients with grade 2 neurotoxicity and in 14 patients with grade 3 neurotoxicity. The main reason that patients could not have reintroduction FOLFOX4 was early progression before reducing neurotoxicity to grade 1. The period from discontinuation of FOLFOX4 to disease progression was 88.5 days in partial response (PR) cases and 58 days in stable disease (SD) cases. PR cases took longer until disease progression than SD cases.


CONCLUSIONS
The incidences of neurotoxicity were similar in Japanese patients compared with those reported in Western studies. These findings provide useful information for clinicians and patients using oxaliplatin.
Matsuda
Masanori
M
Division of Medical Oncology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Japan.
Matsusaka
Satoshi
S
Kuboki
Yasutoshi
Y
Itimura
Takashi
T
Ogura
Mariko
M
Suenaga
Mitsukuni
M
Syouji
Daigo
D
Watanabe
Chie
C
Chin
Keisho
K
Mizunuma
Nobuyuki
N
Hatake
Kiyohiko
K
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D000077150:Oxaliplatin; D012189:Retrospective Studies
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil