Phase II study of paclitaxel, ifosfamide, and cisplatin as second-line treatment in relapsed small-cell lung cancer

Purpose: The aim of the present phase II study was to evaluate the efficacy of the paclitaxel, ifosfamide, and cisplatin (PIC) combination in relapsed small-cell lung cancer (SCLC), Patients and Methods: Eligible patients were those with SClC who hold progr essed or relapsed after therapy with carboplatin and etoposide (with or wit hout chest radiotherapy). The PIC regimen consisted of paclitaxel 175 mg/m( 2) on day 1, ifosfamide 5 g/m(2) divided over days 1 and 2, and cisplatin 1 00 mg/m(2) divided over days 1 and 2; PIC was given every 21 days with gran ulocyte colony-stimulating factor support. Results: Thirty-three patients (30 men and three women) were entered onto t he study (median age, 62 years [range, 55 to 70 years]; median performance status, 1 [range, 0 to 21). Metastatic sites at study entry included the ly mph nodes (n = 13 patients), bone (n = 9), liver (n = 5), brain (n = 6), lu ng nodules (n = 8), adrenal glands (n = 9), and other (n = 2) Responses inc luded eight complete remissions and 16 partial remissions (overall response rate, 73% [24 of 33 patients]). Five patients had stable disease and two h ad progressive disease. Median time to progression and overall survival wer e 21 and 28 weeks, respectively. The 1-year survival rate was 12%, with two patients alive without evidence of disease at 76 and 104 weeks since PIC i nitiation. Grade 3 and 4 toxicities included neutropenia in 30 patients (24 173%] developed grade 4 neutropenia [ < 5 days]) and febrile neutropenia i n six patients (18%); grade 3 or 4 thrombocytopenia was seen in nine patien ts (27%). No grade 3 neuropathy was observed; grade 1 or 2 CNS toxicity was seen in five patients, there was no renal toxicity, grade 2 myalgias were seen in nine patients, grade 2 diarrhea was seen in one patient, and grade 3 nausea or vomiting was seen in seven patients. There were no treatment-re lated deaths. Conclusion: In the present phase II study, the PIC combination seemed highl y active and tolerable in patients with relapsed SCLC when it was administe red as second-line treatment. Given the present experience, an evaluation o f the PIC regimen as front-line treatment of SCLC is planned. J Clin Oncol 19:119-126. (C) 2001 by American Society of Clinical Oncology.