Measures of oxaliplatin-induced neutrotoxicity in 187 patients with FOLFOX4

Abstract

14552 Background: Oxaliplatin-based regimen (FOLFOX regimen) for patients with colorectal cancer have improved survival. Neurotoxicity is the most frequent dose-limiting toxicity of oxaliplatin. Various strategies and pharmacologic agents are currently under investigation to prevent or treat oxaliplatin-induced neurotoxicity. One of them is Stop-and-Go strategy based on the observation of reversibility of the neurotoxic symptoms after discontinuation of oxaliplatin. Stop-and-Go concept will prolong the time of oxaliplatin-based therapy as long as antitumor efficacy is still maintained. Methods: Patients with a histologically verified advanced colorectal carcinoma were eligible for the study. From April 2005 to March 2006 at Cancer Institute Hospital, 187 patients whom treated with bimonthly oxaliplatin-based regimen (FOLFOX4) were enrolled. An oxaliplatin specific neurotoxicity scale are distinct from the National Cancer Institute common toxicity criteria classification (CTC-AE vol. 3). This study was performed to carefully assess the onset and duration to recovery of oxaliplatin neurotoxicity and resumption rate of FOLFOX4. Results: Neurotoxicity was observed in 72 patients with Grade 1, 56 patients with Grade 2 and 33 patients with Grade 3. Oxaliplatin-induced cumulative neurotoxicity develops progressively. The median cumulative doses of oxaliplatin were 170 mg/m2 with Gr. 1; 845.8 mg/m2 with Gr. 2; and 850 mg/m2 with Gr. 3. The median time to onset were 16 days with Gr. 1; 174 days with Gr. 2; and 177 days with Gr. 3. The median time to recovery after stopping the therapy and the median time to progression during the discontinuation of oxaliplatin were 56 and 59 days, respectively, in patients allocated to Gr. 2 compared with 106 and 73 days, respectively, in patients allocated to Gr. 3. The recovery time during the discontinuation showed a statistically significant reduction of the values in the Gr. 2 but not in Gr. 3 (p = 0.0024). The resumption rates of oxaliplatin were 73.7% with Gr. 2 and 46.4% with Gr. 3. Conclusions: Our results may focus to manage time course of Stop-and-Go strategy in clinical practice. No significant financial relationships to disclose.