Cisplatin neuropathy. Clinical, electrophysiologic, morphologic, and toxicologic studies

Area of Science:

• Neuroscience
• Oncology
• Pharmacology

Background:

• Cisplatin is a widely used chemotherapy agent for ovarian cancer.
• Peripheral neuropathy is a known dose-limiting toxicity of cisplatin.
• The specific mechanisms and early manifestations of cisplatin-induced neuropathy require further elucidation.

Purpose of the Study:

• To prospectively investigate the development and characteristics of cisplatin-induced peripheral neuropathy in ovarian cancer patients.
• To correlate clinical findings with electrophysiologic and nerve pathology data.
• To examine platinum distribution in nervous system tissues.

Main Methods:

• Prospective study of 11 ovarian cancer patients receiving monthly cisplatin chemotherapy.
• Monthly neurologic examinations including sensory and reflex testing.
• Nerve conduction velocity studies of median, peroneal, and sural nerves.
• Histopathologic examination of peripheral nerves and measurement of platinum concentrations in nervous system tissues.

Main Results:

• Ten of 11 patients developed distal sensory neuropathy.
• Early signs included decreased vibratory sensibility in toes and loss of ankle jerks.
• Continued cisplatin therapy led to paresthesias in four patients; strength remained unaffected.
• Sural nerve responses diminished, and axonal degeneration was observed in nerve biopsies.
• Platinum concentrations were similar in tumor, sural nerves, and spinal ganglia, but lower in the brain.

Conclusions:

• Cisplatin chemotherapy commonly induces sensory peripheral neuropathy in ovarian cancer patients.
• Early detection of neuropathy involves sensory and reflex changes.
• Axonal degeneration of peripheral nerves is a key pathological finding.
• Higher platinum concentrations in peripheral nerves compared to the brain may explain the selective toxicity.