Predictors of oxaliplatin-induced peripheral neuropathy in patients with advanced colorectal cancer (CRC).

Abstract

619 Background: Chemotherapy-induced neuropathy (CINP) is one of the major dose-limiting toxicities of oxaliplatin. The purpose of this study was to identify early predictors of CIPN and investigate the feasibility of using nerve conduction studies (NCS) to monitor CINP. Methods: Under IRB-approved protocol, we systematically examined patient-reported symptoms, neurological tests and bilateral NCS of the peroneal, superficial peroneal and sural nerves every 3 weeks before each dose of oxaliplatin (75-130 mg/m2) in 12 CRC patients receiving 8 to 13 cycles of XELOX. The severity of neuropathy was graded by the NCI Common Toxicity Criteria (CTC v.4.0) and the Oxaliplatin-Specific Neurotoxicity Scale (OSNS). Results: At the end of chemotherapy three of 12 patients developed peripheral sensory neuropathy CTC grade 3, five had grade 2, and four had grade 1 (3 of them had no self-reported symptoms with loss of Achilles tendon reflexes). At the eighth cycle test only 4 patients experienced CTC grade 2 criteria, but 7 of 12 patients had paresthesias persisting between the cycles of chemotherapy (OSNS grade 2 or higher). Development of grade 2 CINP by CTC or OSNS criteria by the eights cycle of chemotherapy was not associated with the total dose of oxaliplatin received (ANOVA p = 0.86 and 0.78 accordingly), but was significantly associated with administration of concomitant medication (Spearman correlation = 0.62, p = 0.03 for OSNS and 0.6, p = 0.04 for CTC grade 2 CINP). Presence of grade 2 or higher sensory neuropathy before the 8th cycle of oxaliplatin was significantly associated with development of grade 3 CINP by the time of chemotherapy completion (Spearman correlation = 0.8, p = 0.001). The maximal CINP grade that patients have reached during chemotherapy was also significantly associated with concomitant medication use (Spearman correlation = 0.76, p = 0.004). Conclusions: Concomitant administration of medications was the only factor significantly associated with severity of CINP in our study cohort. Further study is needed to verify if it is associated with altered bioavailability of oxaliplatin. No significant financial relationships to disclose.