Can severe vincristine neurotoxicity be prevented?

Abstract

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.

Hepatotoxicity of Chemotherapy

“…Transient aminotransferase elevations, confirmed on rechallenge, have also been reported in a single case [96]. Alkaline phosphatase elevations predict delayed clearance of vincristine and may lead to increased neurotoxicity [97].…”

Chemotherapy of Childhood Acute Lymphoblastic Leukemia

“…Some authors believe that toxicity is related to total cumulative dose [39][40][41], while others have stressed the importance of individual doses and the value of using serum alkaline phosphatase as a guide for dose reduction [34, 40,42]. At present, no guidelines exist for dose modification based on hepatobiliary dysfunction.…”

Horse Gram Seed Germination Inhibition Profiles in Response to Antimitotic Compounds

“…It would therefore be worthwhile to clinically investigate the likelihood of HST-K drug as a possible cost-effective and safer alternative to vinblastine. Likewise, adverse effects have also been reported for vincristine therapy [21]- [23], which should be considered despite the fact that vincristine inhibited horse gram significantly as compared to its inhibition of green gram [3]. The efficacy of the K-drug therefore deserves to be compared vis-à-vis both vinblastine as well as vincristine in clinical trials.…”