Published in:
01-04-2007 | PHASE II STUDIES
Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: Final results of a randomised, controlled, multicenter phase II study
Published in: Investigational New Drugs | Issue 2/2007
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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 85 mg/m2 given biweekly and weekly folinic acid 500 mg/m2 followed by a 24-h infusion of 5-FU 2000 mg/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 4–6 mg/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: The prospectively defined adequate number of patients needed to provide power for the primary outcome could not be achieved. 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. Overall response rates were 16% and 24% and overall survival 15.1 months and 17.4 months for Treatment A and Treatment B, respectively. Between Treatment A and Treatment B there were no major differences when considering worst neurotoxicity during the study period (p=0.46). Grade 3/4 neurotoxicity occured in 4 patients with Treatment A vs. 6 patients with Treatment B. There were no major differences between both groups in each category of the PNP score.
Conclusions: Based on the small number of patients and low statistical power of our study definite conclusions regarding efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer cannot be drawn.