Vincristine neurotoxicity. Pathophysiology and management

Abstract

Vincristine is an antineoplastic drug with a broad spectrum of activity against haematological malignancies and childhood sarcomas. Besides useful activity, it lacks the usual emetic and myelotoxicity of anticancer drugs, but its use is limited by neurotoxicity. The neurotoxicity commonly manifests as reduced motility of the intestines resulting in constipation, and peripheral neuropathy which is predominantly sensory in nature. The early symptoms include numbness and tingling of hands and feet which is accompanied by loss of deep tendon reflexes. In its more severe form, muscle weakness develops which is more marked in distal muscles of the hands and feet. Other manifestations of neurotoxicity include ocular palsies, hoarseness of voice, and autonomic neuropathy in the form of postural hypotension and atony of the urinary bladder. The neurotoxicity is dose related and cumulative with repeated dosage such that the drug therapy has to be stopped after a cumulative dose of 30 to 50 mg. The neurotoxicity is usually reversible on interruption of the therapy, but the recovery is slow and takes several months. There are no specific antidotes which have established usefulness against neurotoxicity.