Can severe vincristine neurotoxicity be prevented?

Neurotoxicity in vincristine treatment has generally been considered a consequence of the cumulative dose of the drug, and liver dysfunction had been recognised as an indication to reduce the dosage. We demonstrate that neurotoxicity is also related to individual doses and that even when there is no other evidence of liver dysfunction, a raised level of serum alkaline phosphatase may predict severe neurotoxicity. Exposure to vincristine following IV injection of the drug was studied in 27 subjects by measuring the area under the vincristine plasma concentration time curve (AUC 0-infinity). A statistically significant relationship was found between the AUC0-infinity and the degree of neurotoxicity. The AUC0-infinity was related both to dose and to elevation of serum alkaline phosphatase, suggesting that elimination of the drug is impaired when serum alkaline phosphatase is raised. Among patients with elevated serum alkaline phosphatase, a small reduction in the dose of the drug resulted in lower vincristine plasma AUC0-infinity and less neurotoxicity.