Our previous randomised trial in patients with advanced ovarian cancer indicated a significant response and survival advantage for those receiving high-dose (100 mg/m2) as compared with low-dose (50 mg/m2) cisplatin in combination with cyclophosphamide (750 mg/m2). However, this was accompanied by more toxicity; peripheral neuropathy was troublesome, with 32% of patients experiencing > or = WHO grade 2 at the cisplatin dose of 100 mg/m2. Nimodipine is a calcium-channel antagonist that has provided protection from cisplatin-induced 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 chemotherapy in an open-label non-randomised trial. This led us to initiate a double-blind, placebo-controlled, randomised trial in patients with ovarian cancer, which was prematurely discontinued because of problems with nausea and vomiting, leading to poor patient compliance, that were not predicted by the pilot study. These studies did not demonstrate a neuroprotective effect for nimodipine. The primary efficacy variable, i.e, the neurotoxicity score at the end of treatment, gave a significantly lower mean for placebo patients than for nimodipine patients. This report details our experience and discusses the reasons for premature termination of the randomised trial.