Evaluation of neurotoxicity induced by paclitaxel second-line chemotherapy

The most important cytotoxic drugs for the treatment of ovarian cancer, pla tinum compounds and paclitaxel, are known to induce neurotoxicity, which is dose limiting when higher paclitaxel doses are used or platinum-pretreated patients are treated. The absolute dose of paclitaxel per course has been demonstrated to be an important risk factor for the development of neurotox icity. The role of cumulative dose, treatment duration and infusion schedul e as additional risk factors are still in debate, and are therefore evaluat ed in this study. This study evaluates paclitaxel induced neurotoxicity in 38 patients, most of whom had already received platinum treatment, receivin g either 135 or 175 mg/m(2) as 3-h or 24-h infusion. Patients were compared with an age-matched control group. A detailed questionnaire and neurophysi ological measurements including vibration perception threshold were used. O verall, the majority of patients (76%) developed some degree of neurotoxici ty, but symptoms were usually mild or moderate with no grade 3/4 neurotoxic ity observed. Age has been demonstrated to be an important risk factor for the development of neurotoxicity. Furthermore, the higher. dose per course showed a significant impact on neurotoxicity, while the different infusion schedules were of minor importance. Vibration threshold perception, 2-point discrimination, a walking-the-line test, and reports of paresthesias were shown to be the most sensitive and useful parameters for neurotoxicity eval uation, Neurotoxicity is a common adverse event during paclitaxel chemother apy in platinum-pretreated patients. A clinically useful test panel compose d of a detailed history and the above three easily performed neurophysiolog ical evaluations should be incorporated into future studies evaluating new drugs, treatment modifications, new combinations, and potential modulators of chemotherapy-induced neurotoxicity.