Phase 1 trial of lipoplatin and gemcitabine as a second-line chemotherapy in patients with nonsmall cell lung carcinoma.

BACKGROUND : Lipoplatin is a new liposomal cisplatin that already has been tested in solid tumors, with encouraging results. The purpose of the current study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of a 21-day regimen of lipoplatin plus a fixed dose of gemcitabine in patients with refractory or resistant nonsmall cell lung carcinoma (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status of </=2. METHODS : The lipoplatin dose was escalated at 100 mg/m(2) by increments of 10 mg/m(2) on Days 1 and 8, with gemcitabine at a dose of 1000 mg/m(2) administered on Days 1 and 8, repeated every 21 days. Hematopoietic growth factors were not allowed. Thirteen patients with advanced stage NSCLC who had been pretreated with platinum combination chemotherapy were enrolled in this phase 1 trial. At least 3 patients were entered at each dose level. RESULTS : At the fourth dose level, the DLT was reached (grade 3 neutropenia [according to World Health Organization criteria] in 3 of 4 patients 75%]; the fourth patient demonstrated degradation of performance status). Therefore, the third dose level (lipoplatin at a dose of 120 mg/m(2)) was defined as the MTD. At the same dose level, 2 of 4 patients had grade 3 thrombocytopenia. At the fourth dose level, 1 patient achieved a partial response and 1 patient had stable disease. Another patient achieved stable disease at the second dose level. Therefore, the overall disease control rate was 23% (3 of 13 patients). The median overall survival was 29 weeks (range, 4 weeks-59 weeks) and the median time to disease progression was 12 weeks (range, 3 weeks-36 weeks). CONCLUSIONS : The pharmacokinetic profile of the 2 compounds used in the current study are not modified when they are administered according to the schedule evaluated in this trial. When one considers that the patients in the current study had refractory or resistant NSCLC, the authors concluded that the combination of lipoplatin administered at a dose of 120 mg/m(2) and gemcitabine administered at a dose of 1000 mg/m(2) on Days 1 and 8 every 3 weeks needs to be studied further in phase 2 trials. Cancer 2008. (c) 2008 American Cancer Society.