Background: For colorectal cancer patients treated with the chemotherapy drug oxaliplatin, oxaliplatin-induced peripheral neuropathy (OIPN) is a serious side effect. We conducted an observational comparative effectiveness study to evaluate whether several potential preventives reduced the rate of OIPN diagnosis in the two years following chemotherapy initiation. Methods: This was a retrospective cohort study that utilized the Surveillance, Epidemiology, and End Results database combined with Medicare claims (SEER-Medicare). Eligible patients were diagnosed with colorectal cancer between 2007-2015, 66 years of age or older, and received at least two cycles of oxaliplatin. We used two definitions to denote diagnosis of OIPN: OIPN 1 (diagnosis codes specific to CIPN) and OIPN 2 (additional codes for peripheral neuropathy). Multinomial propensity score weighting was used to balance potential confounders. The Fine-Gray subdistribution hazards model was used to perform a competing risk, time to event analysis for diagnosis of OIPN. Results: There were 4,482 subjects analyzed for the outcome of OIPN 1 (n = 477, 10.1%), and 4,561 for OIPN 2 (n = 1,191, 26.1%). Duloxetine, venlafaxine (marginally significant for OIPN 1), opioids, and minocycline were associated with a decreased rate of OIPN according to both definitions. In addition, memantine and neuromuscular therapy were associated with a decreased rate of OIPN 1 but not OIPN 2. Gabapentin and pregabalin exposure was associated with an increased rate of OIPN diagnosis according to both definitions. Mixed results were obtained for nortriptyline and cannabinoids. Conclusions: This study revealed several potentially effective preventive options for OIPN in colorectal cancer patients receiving oxaliplatin. A limitation of this study is the observational design which cannot directly inform treatment guidelines. However, evidence from this study may serve as preliminary data to support a future randomized clinical trial.

Abbreviations: sHR, subdistribution hazard ratio; CI, confidence interval; ref, reference group.