Peripheral Neuropathy Due to Biweekly Paclitaxel, Epirubicin and Cisplatin in Patients with Advanced Ovarian Cancer
We assessed the peripheral neuropathic changes induced by biweekly combination chemotherapy including paclitaxel 100–165 mg/m2 (in a 3-h infusion), epirubicin 75 mg/m2 and cisplatin 50 mg/m2 (TEC) in patients with advanced ovarian cancer. Neurologic evaluation, including a standardized questionnaire, bed-side neurological examination, and quantitative determination of vibratory perception thresholds (VPT) and grip strength took place before therapy, after 3 and 6 cycles, and thereafter whenever possible. During chemotherapy all patients received granulocyte colony-stimulating factor from days 2 to 12. Pretreated patients received amifostine two times, before epirubicin and before cisplatin administration. Neuropathic symptoms developed in 11/13 non-pretreated patients and in 7/9 chemotherapy-pretreated patients. Neuropathic signs developed in all patients. Neuropathic symptoms and signs were predominantly sensory in character. VPT changes developed primarily in the feet. According to National Cancer Institute of Canada Common Toxicity Criteria, grade 3 peripheral neuropathy after 6 cycles developed in 1/6 and 2/4 non-pretreated patients who received TEC containing paclitaxel 150 and 165 mg/m2, respectively. We conclude that peripheral neuropathy is dose-limiting in chemonaïve patients treated with biweekly TEC combination chemotherapy, at paclitaxel dose level 165 mg/m2 in a 3-h intravenous administration.