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Misonidazole neuropathy. A prospective study.

B Melgaard¹, O Køhler, H Sand Hansen

¹Neurology Service, Finseninstituttet, Copenhagen, Denmark.

Journal of Neuro-Oncology

|November 1, 1988

Summary

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The radiosensitizing drug misonidazole increased the risk of developing polyneuropathy in patients with larynx and pharynx cancer. Higher misonidazole concentrations correlated with increased neuropathy risk.

Area of Science:

Oncology
Neurology
Clinical Pharmacology

Background:

Cancer patients undergoing radiotherapy may experience side effects.
Radiosensitizing agents are used to enhance radiation therapy effectiveness.
Polyneuropathy is a potential adverse effect of certain cancer treatments.

Purpose of the Study:

To investigate the incidence of polyneuropathy in cancer patients treated with misonidazole.
To explore the relationship between misonidazole dosage, pharmacokinetics, and neuropathy development.
To assess changes in vibration perception threshold as an indicator of neuropathy.

Main Methods:

Double-blind, placebo-controlled clinical trial.
Recruitment of patients with larynx and pharynx cancer.

Related Experiment Videos

Administration of misonidazole or placebo, with monitoring for neuropathy and vibration perception thresholds.

Pharmacokinetic analysis of misonidazole plasma concentrations.

Main Results:

Polyneuropathy developed in 14/36 patients receiving misonidazole versus 2/34 in the placebo group.
Increased vibration perception thresholds were observed in all neuropathy patients and some asymptomatic patients.
High peak plasma concentrations and area under the plasma concentration curve of misonidazole correlated with neuropathy development.

Conclusions:

Misonidazole significantly increases the risk of polyneuropathy in patients with larynx and pharynx cancer.
Pharmacokinetic parameters, specifically high plasma concentrations of misonidazole, are associated with neuropathy.
Vibration perception threshold may serve as an early indicator of drug-induced neuropathy.