From the Guidelines
The correct answer is (a) vinca alkaloids. Vinca alkaloids, which include vincristine, vinblastine, and vinorelbine, commonly cause severe peripheral neuropathy as a dose-limiting toxicity, as noted in the study by 1. These drugs work by binding to tubulin and preventing microtubule formation, which disrupts cell division. However, this same mechanism affects the microtubules in peripheral nerve axons, leading to axonal degeneration and the development of peripheral neuropathy. Symptoms typically include numbness, tingling, and pain in a "glove and stocking" distribution, along with loss of deep tendon reflexes. The neuropathy is often dose-dependent and can be severe enough to require dose reduction or discontinuation of therapy. Some key points to consider:
- Vinca alkaloids are well-known to cause severe peripheral neuropathy, as discussed in the guidelines by 1 and 1.
- While cisplatin (option d) can also cause peripheral neuropathy, it is typically less severe than that caused by vinca alkaloids.
- Cyclophosphamide (option b) and cytarabine (option c) are not primarily associated with significant peripheral neuropathy as their major toxicities, as noted in the studies by 1, 1, and 1.
- The prevention and management of chemotherapy-induced peripheral neuropathy are crucial to improve the quality of life of patients, as emphasized in the guidelines by 1 and 1. It's essential to prioritize the management of peripheral neuropathy to minimize its impact on patients' morbidity, mortality, and quality of life, as highlighted in 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
The answer is: (d) cisplatin. Severe peripheral neuropathy is a complication of cisplatin, particularly when used at higher doses or greater frequencies than recommended 2. Key characteristics of this neuropathy include:
- Paresthesias in a stocking-glove distribution
- Areflexia
- Loss of proprioception and vibratory sensation
- Potential for irreversibility
- Increased susceptibility in elderly patients 2 2
From the Research
Severe Peripheral Neuropathy Complications
- Severe peripheral neuropathy is a complication of vinca alkaloids, as evidenced by studies 3, 4, 5, 6, 7
Affected Chemotherapy Agents
- Vinca alkaloids, such as vincristine, are commonly associated with peripheral neuropathy 3, 4, 5, 6, 7
- Other chemotherapy agents, like thalidomide and bortezomib, may also contribute to peripheral neuropathy 5
Characteristics of Peripheral Neuropathy
- Peripheral neuropathy can cause sensory neuropathy, neuropathic pain, motor neuropathy, and autonomic damage 5
- Symptoms may include mechanical allodynia, sensory/tactile disorders, and numbness in the hands and feet 6
Mechanisms and Risk Factors
- The mechanisms underlying vincristine-induced peripheral neuropathy involve the degeneration of dorsal root ganglion and the inhibition of the ubiquitin proteasome system 5
- Risk factors for peripheral neuropathy include diabetes mellitus, alcohol abuse, vitamin deficiencies, and viral infections 5