Paclitaxel-induced neuropathy |
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| Authors: | Postma T J; Vermorken J B; Liefting A J M; Pinedo H M; Heimans J J |
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| Institution: | 1Department of Neurology
2Department of Medical Oncology, Free University Hospital Amsterdam, the Netherlands |
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| Abstract: | Background: Paclitaxel (Taxol®) is a new antineoplasticagent derived from the bark of the western yew, Taxus brevifolia,with important activity against several tumors such as ovariancancer, breast cancer, lung cancer and head and neck cancer.Because it promotes microtubule assembly, neuropathy occursas one of its toxic side effects. Our purpose was to evaluatethe incidence, severity, dose-dependency and reversibility ofpaclitaxel-induced neuropathy. Patients and methods: We prospectivelystudied 27 patients treated with single-agent paclitaxel atthree dose levels. Paclitaxel was administered by 3-hour intravenousinfusion every three weeks in all patients, and if possible,all were evaluated neurologically before paclitaxel, after everyother cycle and after discontinuation of therapy. We used astandardized questionnaire and neurologic examination with emphasison neuropathic symptoms and signs. The severity of symptomsand signs was scored. Quantitatively, vibratory perception threshold(vibrameter) and grip strength (dynamometer) were measured.Results: Six, 14 and seven patients were treated with 135 mg/m2,175 mg/m2 and 250–300 mg/m2, respectively. Neuropathicsymptoms occurred in 50%, 79% and 100%, neuropathic signs in83%, 86% and 100%, and dose-limiting neurotoxicity in 0%, 21%and 71% of patients, respectively. Neurotoxicity progressedwith higher cumulative dose and was more pronounced with higherdose per course. Paclitaxel-induced neuropathy was predominantlysensory in character, though minor motor signs were present.Follow-up data of 12 patients after discontinuation of paclitaxeltherapy showed that paclitaxel-induced neuropathy is at leastpartially reversible. Conclusions: Paclitaxel-induced neuropathyis a dose-dependent phenomenon, occurring with higher cumulativedose and higher dose per cycle. Using 3-weekly 3-hour infusionsof paclitaxel, dose-limiting neurotoxicity can be expected inpatients treated with 250 mg/m2 or more each cycle. dose-dependency, neuropathy, paclitaxel, reversibility |
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