A patient with breast cancer undergoing chemotherapy develops numbness and tingling in the hands and feet during treatment cycles. Which chemotherapeutic agent is most likely responsible for this peripheral neuropathy?

• A. Vincristine
• B. Doxorubicin
• C. Paclitaxel
• D. Cyclophosphamide

Answer: (A)

Peripheral neuropathy from chemotherapy is most classically seen with drugs that disrupt microtubules. Vincristine is a vinca alkaloid that binds tubulin and prevents microtubule polymerization, which stops cell division but also cripples axonal transport in neurons. Neurons rely on microtubule-based transport to move essential materials along the long axons, so this disruption commonly presents as numbness and tingling in the hands and feet during treatment cycles. This neuropathy is a dose-limiting toxicity and can be predominantly sensory, sometimes with motor or autonomic involvement.

Other drugs in the list cause different primary toxicities: doxorubicin is mainly cardiotoxic and myelosuppressive, paclitaxel can also cause neuropathy but through different mechanisms related to microtubule stabilization, and cyclophosphamide is more associated with myelosuppression and hemorrhagic cystitis. Thus, the neuropathic presentation during chemotherapy most strongly points to vincristine.