Oxaliplatin-induced peripheral neuropathy with hepatic arterial versus intravenous infusion in metastatic colorectal cancer.

Abstract Background – Oxaliplatin, a major drug in metastatic colorectal cancer (mCRC), is responsible for a cumulative, dose-limiting peripheral neuropathy (PN). Whether the hepatic arterial infusion (HAI) route can limit oxaliplatin-induced PN in comparison with intravenous (IV) route has not been specifically explored so far. Methods – We compared the frequency and severity of PN in oxaliplatin-naive patients with mCRC included in trials that evaluated treatment with oxaliplatin administered either by HAI (ACCORD 04, CHOICE, OSCAR, and PACHA-01 trials) or by IV route (FFCD 2000-05 trial). We retrieved anonymized, prospectively collected data from trial databases for the ACCORD 04, CHOICE and FFCD 2000-05 trials; and through a review of Gustave Roussy patients’ electronic medical records for PACHA-01 and OSCAR trials. The primary endpoint was the incidence of clinically significant PN (grade 2 to 4) according to the cumulative dose of oxaliplatin received. Secondary endpoints were time to onset of neuropathy as a function of the cumulative dose of oxaliplatin, discontinuation of oxaliplatin for neurotoxicity, and safety. Results – 363 patients were included (IV, 300; HAI, 63). 180 patients in the IV group (60%) and 30 patients in the HAI group (48%) developed clinically significant PN, with no significant difference between the two groups (p = 0.23). No difference was shown in the time to onset of PN, neither (p = 0.23). Conclusion – The administration of oxaliplatin HAI rather than IV in the treatment of mCRC does not seem to reduce the incidence, precocity and severity of PN.