CLINICAL-TRIALS OF NIMODIPINE AS A POTENTIAL NEUROPROTECTOR IN OVARIAN-CANCER PATIENTS TREATED WITH CISPLATIN

Our previous randomised trial in patients with advanced ovarian cancer indicated a significant response and survival advantage for those rec eiving high-dose (100 mg/m(2)) as compared with low-dose (50 mg/m(2)) cisplatin in combination with cyclophosphamide (750 mg/m(2)). However, this was accompanied by more toxicity; peripheral neuropathy was trou blesome, with 32% of patients experiencing greater than or equal to WH O grade 2 at the cisplatin dose of 100 mg/m(2). Nimodipine is a calciu m-channel antagonist that has provided protection from cisplatin-induc ed neurotoxicity in a rat model system. We performed a pilot study in 50 patients that demonstrated the feasibility of co-administration of nimodipine in a chronic oral dosing schedule with cisplatin-based chem otherapy in an open-label non-randomised trial. This led us to initiat e a double-blind, placebo-controlled, randomised trial in patients wit h ovarian cancer, which was prematurely discontinued because of proble ms with nausea and vomiting, leading to poor patient compliance, that were not predicted by the pilot study. These studies did not demonstra te a neuroprotective effect for nimodipine. The primary efficacy varia ble, i.e, the neurotoxicity score at the end of treatment, gave a sign ificantly lower mean for placebo patients than for nimodipine patients . This report details our experience and discusses the reasons for pre mature termination of the randomised trial.