Peripheral neuropathy with microtubule-targeting agents: occurrence and management approach

Abstract

Microtubule-targeting agents (MTAs), which include vinca alkaloids, taxanes, and the recently introduced epothilone, ixabepilone, are widely used chemotherapeutic agents for treatment of patients with cancer. MTAs interfere with the normal structure and function of microtubules, leading to cell-cycle arrest and tumor cell death. Microtubule function is critical to normal neuronal function, thus MTA therapy is commonly associated with some form of neuropathy. There is poor agreement between tools for clinical assessment of MTA-associated peripheral neuropathy, and standardization of grading scales is needed to reduce variability. For a majority of patients, MTA-associated neuropathy is mild to moderate in intensity and reversible, but it can be severe and resolve incompletely. The incidence and severity of MTA-associated neuropathy is drug, dose, and schedule dependent. The first-generation vinca alkaloids (eg, vincristine) are associated with severe mixed sensory and motor neuropathy, whereas the newer vinca alkaloids (eg, vinorelbine, vinflunine) induce a milder sensory neuropathy. Taxane-associated sensory neuropathy occurs more often with standard (polyoxyethylated castor oil-based) and albumin-bound paclitaxel than with docetaxel. The incidence and presentation of peripheral neuropathy with ixabepilone, alone or in combination with capecitabine, are similar to that with taxanes. Management of neuropathy may involve reducing or delaying the MTA dose, or in severe persistent or disabling cases discontinuing treatment. Reversal of neuropathy after dosage intervention appears to be more rapid with ixabepilone than with other MTAs.