VINCRISTINE AND NEUROPATHY


Editors:

Elham Reshid and Hailemariam Shimelis

Vincristine is a chemotherapeutic drug under the class of vinca alkaloid, first approved by FDA before 1984. It works by inhibiting microtubule assembly in formation of the mitotic spindle, resulting in an arrest of dividing cells and cell death. Vincristine is usually used in combination with other chemotherapy drugs to treat some leukemias, lymphomas, and childhood cancers, as well as several other types of cancer and some non-cancerous conditions.

Vincristine is available as a solution to be injected intravenously. The standard maximum adult intravenous (IV) vincristine dose is 2 mg IV per dose given at weekly intervals. Among the side effects, neuropathy is the dose-limiting side effect of all vinca alkaloids, with vincristine being the most notorious. This side effect is most likely results from impaired microtubule function involved in axonal transport.

Vincristine produces a predictable mixed motor and sensory neuropathy, as well as an autonomic neuropathy. Approximately, one half of patients develop a sensorimotor neuropathy at normal doses of 1.4 mg/m2/ week. The actual dose and the interval between doses appear to be important in the development of neuropathy.

Treatment with IV vincristine at doses above 5 mg leads to a dose -dependent neuropathy with sensory symptoms but higher cumulative doses at around 30 to 50 mg are needed for the development of motor symptoms. Similarly, intervals of 1 week are more toxic than 3 weeks, even at the same cumulative dose.

There are several lines of evidence supporting the dose-related vincristine-induced neuropathy. Patients with clinically significant neuropathy during vincristine therapy should be monitored closely and considered for dose-reduction. Although discontinuation has been proposed as an option, dose reduction usually reverse most sign and symptoms without discontinuation.

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References:

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682822.html  

http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/vincristine  

http://www.ncbi.nlm.nih.gov/pubmed/15781834

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