Carbamazepine does not prevent Oxaliplatin-Related Neurotoxicity in Patients with Advanced Colorectal Cancer: Final Results of a Randomised, Controlled, Multicenter Phase II Study

Background: Oxaliplatin-induced neurotoxicity is a growing, relevant clinical problem. In this study we evaluated the efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer. Methods: Chemotherapeutic treatment consisted of oxaliplatin 85mg/m² given biweekly and weekly folinic acid 500mg/m² followed by a 24-hour infusion of 5-FU 2000mg/m² (FUFOX). One cycle consisted of six consecutive weeks of treatment followed by two weeks of rest (=Treatment B). For Treatment A carbamazepine was added in a dosage for targeted plasma levels of 4–6mg/L. Neurotoxicity was regularly assessed using a specific scale. Moreover, an evaluation of chronic sensory symptoms and a neurologic examination including tests for vibrational sense, strength and deep tendon reflexes were added creating a peripheral neuropathy (PNP) score. Results: 19 patients were assigned to Treatment A and 17 to Treatment B. At baseline, the distribution of all clinicopathologic variables was comparable between the two groups. The addition of carbamazepine did not alter anti-tumor activity of oxaliplatin in terms of response rate and median progression free and overall survival. Between Treatment A and Treatment B there were no statistical significant differences when considering worst neurotoxicity during the study period (p=0,46). Both groups were also similar when comparing the occurrence of grade 3/4 neurotoxicity (p=0,72). There were no statistical significant differences in each category of the PNP score. Conclusions: Carbamazepine does not affect anti-tumor activity of oxaliplatin, but has no relevant protective effect regarding the development of acute and chronic oxaliplatin-induced neurotoxicity.