What medication is associated with severe peripheral neuropathy: Vinca alkaloids, Cyclophosphamide, Cytarabine, or Cisplatin?

From the Guidelines

The answer is A. Vinca alkaloids. Severe peripheral neuropathy is a well-known complication of vinca alkaloids such as vincristine, vinblastine, and vinorelbine, as stated in the study by 1. These chemotherapeutic agents work by binding to tubulin and preventing microtubule formation, which disrupts cell division. However, this mechanism also affects the axonal transport in peripheral nerves, leading to axonal degeneration and subsequent neuropathy. Patients typically experience numbness, tingling, and pain in a "glove and stocking" distribution, along with loss of deep tendon reflexes. The neuropathy is dose-dependent and can be dose-limiting.

Some key points to consider:

• Vinca alkaloids can cause small fibre neuropathy, leading to painful sensation of burning feet (and/or hands) and even lancinating pain, as mentioned in the study by 1.
• The clinical picture may be asymmetrical and predominantly involves proprioception sense but does not exclude the motor system, as stated in the study by 1.
• While cisplatin (option D) can also cause peripheral neuropathy, it is typically less severe than that caused by vinca alkaloids, as mentioned in the study by 1.
• Cyclophosphamide (option B) and cytarabine (option C) are not primarily associated with severe peripheral neuropathy, though they have other significant toxicities, as stated in the study by 1.

Overall, the evidence suggests that vinca alkaloids are the most likely cause of severe peripheral neuropathy among the options listed, due to their mechanism of action and the clinical presentation of the neuropathy, as supported by the study by 1.

From the FDA Drug Label

There are reports of severe neuropathies in patients in whom regimens are employed using higher doses of cisplatin or greater dose frequencies than those recommended These neuropathies may be irreversible and are seen as paresthesias in a stocking-glove distribution, areflexia, and loss of proprioception and vibratory sensation. Elderly patients may be more susceptible to peripheral neuropathy

Severe peripheral neuropathy is a complication of D. Cisplatin 2.

From the Research

Severe Peripheral Neuropathy Complications

• Severe peripheral neuropathy is a complication of certain chemotherapeutic agents, including:
  • Vinca alkaloids, such as vincristine 3, 4, 5, 6
  • Platinum-based drugs, such as cisplatin 4, 7
• The symptoms of severe peripheral neuropathy include:
  • Mechanical allodynia
  • Sensory/tactile disorders
  • Numbness in the hands and feet 3
  • Sensorimotor involvement in upper and lower limbs 6
• The development of severe peripheral neuropathy can lead to:
  • Dose reduction or treatment cessation 4, 7
  • Increased mortality 7
  • Permanent disability 5
  • Significant impact on disability and function 6
• The chemotherapeutic agents associated with severe peripheral neuropathy include:
  • Vinca alkaloids 3, 4, 5, 6
  • Platinum-based drugs, such as cisplatin 4, 7
  • Taxanes 4, 7
  • Proteasome inhibitors, such as bortezomib 4, 5
  • Cisplatin is the correct answer as it is a platinum-based drug.