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Misonidazole neuropathy
Abstract:
Neurotoxic side effects of misonidazole with peripheral neuropathy was investigated in two series of patients. The first series consisted of eight patients with carcinoma of the pharynx, larynx or lung who, during treatment with misonidazole, developed peripheral neuropathy dominated by severe sensory symptoms and signs localized mainly to the lower extremities. Misonidazole was given for three to seven weeks in a total dose of 9.6 - 12.6 g/m2 (11 g/m2 or more in four of the patients). The symptoms subsided partially within a few months after cessation of the therapy. Electrophysiological and histological findings indicated axonal neuropathy with loss of large fibres and secondary demyelination. The second series consisted of 70 patients with carcinoma of the pharynx or larynx who, in addition to radiotherapy, were given either placebo or misonidazole over four weeks in a total dose of 11 g/m2. Fourteen patients out of 36 receiving misonidazole (38%) developed peripheral polyneuropathy, mostly in the feet, while this occurred in only two of the 34 patient placebo group.
Insights
Misonidazole treatment can cause neurotoxic side effects, specifically peripheral neuropathy. This study found a significant increase in neuropathy cases among patients receiving misonidazole compared to placebo.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- Misonidazole is a hypoxic cell radiosensitizer used in cancer therapy.
- Peripheral neuropathy is a potential neurotoxic side effect of various treatments.
Purpose of the Study:
- To investigate the neurotoxic side effects of misonidazole, focusing on peripheral neuropathy.
- To determine the incidence of peripheral neuropathy in patients treated with misonidazole.
Main Methods:
- Two series of patients were studied: one with existing neuropathy during misonidazole treatment, and another comparing misonidazole with placebo during radiotherapy.
- Clinical evaluation, electrophysiological studies, and histological examination were used to assess neuropathy.
- Statistical analysis was performed to compare neuropathy incidence between misonidazole and placebo groups.
Main Results:
- In the first series, eight patients developed sensory peripheral neuropathy, characterized by axonal damage and demyelination, which partially resolved after treatment cessation.
- In the second series, 38% of patients receiving misonidazole developed peripheral polyneuropathy compared to only 6% in the placebo group.
- Neuropathy primarily affected the lower extremities, particularly the feet.
Conclusions:
- Misonidazole is associated with a significant risk of developing peripheral neuropathy.
- The neuropathy appears to be an axonal type with secondary demyelination.
- Clinical monitoring for neurotoxic effects is recommended during misonidazole therapy.