NEUROTOXICITY AND OTOTOXICITY OF CISPLATIN PLUS PACLITAXEL IN COMPARISON TO CISPLATIN PLUS CYCLOPHOSPHAMIDE IN PATIENTS WITH EPITHELIAL OVARIAN-CANCER

Purpose: To compare the neurotoxicity and ototoxicity of combination c isplatin plus paclitaxel versus cisplatin plus cyclophosphamide using extensive clinical and instrumental evaluation. Patients and Methods: Forty-six of 51 consecutive patients affected by epithelial ovarian ca ncer seen in our institution between October 1994 and August 1995 ente red the study. After randomization, they were assigned to receive cisp latin 75 mg/m(2) every 3 weeks associated with cyclophosphamide 750 mg /m(2) (CC group, n = 22) or paclitaxel 175 mg/m(2) over a 3-hour infus ion (CP group, n = 24). Treatment was repeated six times in 43 patient s and nine times in 25. Before treatment and after three, six, and nin e courses of chemotherapy, patients underwent clinical and instrumenta l neurologic and otologic examinations. Results: Mild sensory impairme nt was evident even after only three courses of both treatments and si gns and symptoms were more severe at the end of treatment. On clinical grounds only, it was possible to demonstrate after six and nine cours es a difference between CC and CP treatment, due to the involvement in some CP patients of pain and thermal sensory modalities. However, the overall severity of the neuropathy was similar. Audiometric parameter s demonstrated a more negative outcome after treatment in CC compared with CP patients, However, the different severity of the involvement w as closely correlated to this initial difference in audiologic perform ance. Conclusion: Up to nine courses of chemotherapy, the CC and CP sc hedules are similar in terms of severity of neurotoxicity and ototoxic ity when patients are evaluated during and immediately after treatment . With the doses used in our study, these toxicities are not dose-limi ting. Our results suggest that most of the toxic effects observed duri ng the treatment were due to cisplatin. (C) 1997 by American Society o f Clinical Oncology.