BBR 3464 is a novel triplatinum compound that has exhibited anti-tumor activity in both cisplatin-sensitive and cisplatin-resistant, as well as in p53 mutant tumor models. In phase I testing, the dose-limiting toxicities have included myelosuppression and diarrhea. Both an intermittent (day 1 every 21-28 days) and a continuous (dailyx5 days) schedule have been studied, and the intermittent schedule has been chosen for further development. The primary objective of this study was to assess the efficacy of BBR 3464 administered at a dose of 0.9 mg/m i.v. over 1 h every 21 days in patients with small cell lung cancer who have progressed after first-line therapy. Pharmacokinetic analysis was also performed and will be reported. Patients were stratified based on prior response into resistant and sensitive (response duration 3 months or longer) subgroups. Thirty-seven patients were enrolled onto this multicenter study. The median number of cycles delivered was 2 in the resistant subgroup (range 1-12) and 3 in the sensitive subgroup (range 1-8). Most common grade 3/4 hematological toxicities included neutropenia (62%), febrile neutropenia (16%), anemia (10%), fatigue (5%) and hypokalemia (5%). Although no objective responses were seen in 34 evaluable patients, 11 patients (32%) had disease stabilization (four resistant/seven sensitive) with 23 patients (68%) experiencing continued disease progression (12 resistant/11 sensitive). Median time to progression was 53 days in the resistant subgroup [95% confidence interval (CI) 37-63] and 66 days in the sensitive subgroup (95% CI 51-136). The median and 1-year survival rate based on subgroup was 78 (resistant) (95% CI 56-165) versus 209 days (sensitive) (95% CI 83-296) and 6 (resistant) (95% CI 0-17) versus 20% (95% CI 2-38%), respectively. We conclude that the toxicity profile of BBR 3464 in this phase II trial is consistent with the phase I experience. The lack of activity in either patient subgroup, however, does not support further evaluation of this drug as a single agent in this disease.