We conducted a phase I/II study of combination chemotherapy with nedaplatin (NDP) and irinotecan to determine the effects against advanced non-small-cell lung cancer (NSCLC) and to determine the qualitative and quantitative toxicities of the combination chemotherapy. NDP was given on day 1 and irinotecan on days 1 and 8. The treatment cycle was designed to be repeated every 3 weeks. We fixed the dose of irinotecan as 60 mg/m(2) and escalated the NDP dose from a starting dose of 50 mg/m(2) by 10-mg/m(2) increments until the maximum tolerated dose (MTD) was reached. The MTD was defined as the dose level at which at least two of three or three of six patients experienced a dose-limiting toxicity (DLT). Between April 1997 and November 2000, 42 patients were registered in the study. Of the 42 patients, 37 had no prior treatment, 3 had received whole-brain irradiation, 1 had undergone surgical resection, and 1 had had one regimen of chemotherapy before enrolling in this study. In the phase I study, we observed DLTs such as grade 4 neutropenia lasting 7 days and grade 3 diarrhea lasting 1 day in one patient at level 2, grade 3 elevated of GPT in one patient at level 3, and acute myocardial infarction in one patient at level 6. We could not determine the MTD until dose level 6 was reached, so decided on a recommended dose of 100 mg/m(2) NDP, which is recommended for NDP-alone chemotherapy. Because of prolonged neutropenia in the phase I study, we repeated the treatment every 4 weeks in the phase II study. In the phase II study, a total of 16 patients, including 6 patients from the phase I study, were registered and a total of 42 cycles were administered. Grade 3 or 4 neutropenia, grade 3 anemia and grade 3 or 4 thrombocytopenia occurred in 50%, 12% and 7% of cycles, respectively. Febrile neutropenia occurred in eight cycles (19%) but there were no severe infections. Grade 3 elevation of GPT occurred in one patient. Of the 16 patients, 7 had an objective response. Of the 42 patients, 13 achieved a partial response (PR) and the overall response rate was 31.0%. The median duration of PRs was 226 days (range 59 to 646 days). The median survival time was 341 days and the 1-year survival rate was 45.2%. In conclusion, the combination of NDP and irinotecan was highly effective and well tolerated in NSCLC.