We conducted a phase II study of tamoxifen, ifosfamide, epirubicin, and cisplatin (TIEP) chemotherapy in patients with non-small cell lung cancer (NSCLC) who had failed previous chemotherapy, in order to assess the response and toxicity of TIEP. Between November 1997 and May 1999, 25 patients were treated. Twelve of the 25 patients (48%) had been previously treated with cisplatin-based combination chemotherapy. TIEP doses were tamoxifen 60 mg oral twice daily on days 1-3; ifosfamide 2.4 g/m(2) intravenous infusion (IV) 60 min with mesna on day 2; epirubicin 40 mg/m(2) IV bolus on day 2; and cisplatin 50 mg/m(2) IV 60 min on day 2 every 4 weeks for up to six cycles. Seventy one cycles were given to 25 patients, with a median of three cycles (range one to six cycles). All patients were evaluable for toxicity profile and response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 15 patients (60%) during treatment, as well as in 31% of the total courses. Febrile neutropenia occurred in two patients. No toxic death occurred in this study. Grade 3 thrombocytopenia occurred in five patients with five cycles. Toxicities other than myelosuppression were few and mild in severity. After two cycles of treatment, five of 25 patients (20%) had a partial response (95% confidence interval 4.3-35.7%). Among 12 patients previously treated with cisplatin-based chemotherapy, three patients (25%) achieved a partial response. The median time to disease progression was 4.9 months and median survival was 7.7 months. The response rate and median survival were better than in our previous study of salvage chemotherapy with ifosfamide, 5-FU, and leucovorin; and with ifosfamide, epirubicin, 5-FU, and leucovorin. In conclusion, TIEP appears to be an active combination regimen with an acceptable toxicity profile in Chinese patients with NSCLC who have failed previous chemotherapy.