PERIPHERAL NEUROTOXICITY OF TAXOL IN PATIENTS PREVIOUSLY TREATED WITHCISPLATIN

Background. Taxol is a new anticancer drug that acts as a tubulin poly meration enhancer. Its major toxicities are myelosuppression, hypersen sitivity, and mucositis, but it also induces peripheral nerve damage. The use of taxol has recently been proposed for platinum-resistant can cers, but in these cases there is a possibility of cumulative toxicity in the peripheral nervous system. Methods. Twenty-two patients affect ed by a relapse of cisplatin-treated ovarian cancer were examined clin ically and neurophysiologically to determine the evolution of taxol-in duced peripheral somatic and autonomic neurotoxicity and the possible cumulative effect of a combination of taxol and cisplatin. Each patien t was examined before, during, and after taxol treatment (using a dose of 135 or 175 mg/m(2) in 3 hours every 3 weeks). Results. No patients were excluded from the study because of unacceptable toxicities of an y kind. The serial examinations demonstrated that taxol induced onset of (or worsening of preexisting) neuropathic symptoms and signs in alm ost all the patients, The features were those of a distal, symmetrical , sensory polyneuropathy due to an axonopathy. Motor nerves and the au tonomic nervous system were unaffected. Taxol neurotoxicity appeared e arly in the course of the treatment (i.e., after three courses) and wa s not severely disabling, In most cases after the early onset of perip heral neuropathy, stabilization of this side effect occurred. Conclusi ons. Considering the low doses of taxol used in this study, the sensor y nerve damage was unexpectedly severe. It appears that a cumulative, but not dose-limiting, neurotoxic effect occurs using taxol in patient s previously treated with cisplatin.