Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: Final results of a randomised, controlled, multicenter phase II study
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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.
KeywordsOxaliplatin Neurotoxicity Carbamazepine Randomised clinical trial Colorectal cancer
Computational assistance of Caterina Riehle, IMSE TU Munich, is gratefully acknowledged. We also thank Nadine Röthling for assistance with documentation. This study was supported by a grant from Sanofi-Aventis.
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