Pharmacological approaches to ameliorate vincristine neuropathy

Vincristine has been an important agent in the treatment of especially pediatric malignancies for four decades. The dose-limiting side effect of vincristine is peripheral neuropathy resulting in pain, constipation, paresthesisas, and impaired motor function. Besides this neuropathy, other side effects are relatively mild and no serious long-term side effects are known, such as second malignancies or infertility. At present, we still don't know how to prevent or overcome vincristine neuropathy other than by reducing or interrupting therapy, which might lead to a less optimal oncolytic effect. Because of its efficacy and relatively mild non-neurotoxic side effects, it is worthwhile to try to maximize its use as an anticancer agent. Finding ways to ameliorate vincristine neuropathy would therefore be of treat interest. In this thesis two pharmacological approaches are described to achieve this goal. First, we hypothesized that neuropathy might be related to vincristine pharmacokinetics; a higher degree of neuropathy might correlate with a higher systemic exposure. ... Zie: Summary.