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.
Purpose: We performed a retrospective study on the recovery from chronic neurotoxicity and period for discontinuing FOLFOX4 therapy due to neurotoxicity.
Patients and method: 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.
Result: 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.