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

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Abstract
Ten of 11 patients with ovarian cancer receiving cisplatin developed a distal sensory neuropathy, manifested early by decreased vibratory sensibility in toes and depressed ankle jerks and later by uncomfortable paresthesias. Eleven patients receiving cisplatin, 50 mg/m2 monthly (mean total, 580 mg/m2) were studied prospectively with monthly neurologic examinations and conduction velocity determinations of median, peroneal, and sural nerves. Early signs were decreased vibratory sensibility in toes (mean dose, 417 ± 132 mg/m2 [SD]) and loss of ankle jerks (mean dose, 455 ± 86 mg/m2). With continued therapy, four developed paresthesias. Strength was unaffected. Sural nerve responses abruptly disappeared in six patients (mean dose, 383 ± 103 mg/m2). Other conduction velocities remained normal. Electron microscopy of peripheral nerves from four patients showed axonal degeneration and secondary myelin breakdown. Platinum concentrations in three patients were similar in tumor (3.3 μg/g), sural nerves (3.5 μg/g), and spinal ganglia (3.8 μg/g), but lower in brain (0.17 μg/g). This may explain the cisplatin toxicity of peripheral nerves with relative sparing of the central nervous system.