Neurotoxicity of cisplatin and taxol

Since the discovery of the activity of cisplatin in ovarian cancer approximately 15 years ago, there has been little progress in improving survival for patients with this disease. Thus there has been great enthusiasm in the gynecologic oncology community over the results of GOG111, the Gynecologic Oncology Group (GOG) study randomizing suboptimally debulked ovarian cancer patients to cisplatin with either cyclophosphamide or paclitaxel (TaxolR). To date, a median survival increase of 13 months has been seen in patients on the taxol-containing arm (ref. 1; W.P. McGuire, personal communication). Although a confirmatory study is about to be implemented by the European Organization for the Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC), the GOG results are encouraging enough that the majority of ovarian cancer protocols developed over the next decade will probably incorporate some combination of cisplatin and taxol. Since neurotoxicity is now the dose-limiting toxicity of each of these agents, the potential for synergistic toxicity is of major concern, particularly with the tendency for recent protocols to investigate higher doses of both cisplatin and taxol than those used in the GOG study, which were 75 mg m-2 and 135 mg m-2 respectively. This paper will review the clinical manifestations and pathogenesis of the neurotoxicity of cisplatin and taxol as single agents, as well as in combination. The discussion will include several promising compounds which appear to prevent or diminish this sometimes severely disabling neurotoxicity.