Gemcitabine, ifosfamide and paclitaxel in advanced/metastatic non-small cell lung cancer patients: a phase II study.

UNLABELLED: Although platinum-based two-drug combinations represent the elective therapeutic approach for advanced/metastatic NSCLC, there is still interest in exploring the efficacy and tolerability of platinum-free combinations including third generation agents in selected NSCLC population. Based on the satisfying activity of gemcitabine (G), ifosfamide (I) and paclitaxel (T) as single agents in NSCLC, we have designed a phase II study to explore an alternative approach to platinum-containing regimens using a combination of these three drugs. To investigate the activity/toxicity of T 175 mg/m2 on day 1, I 3 g/m2 on day 1 (with Mesna uroprotection) and G 1,000 mg/m2 on day 1-8, every 3 weeks in the treatment of advanced/metastatic NSCLC, 46 patients (38 male, 8 female) with NSCLC were enrolled: mean age 58 (range 33-70); Stage IIIB/IV=15/31; ECOG PS 0-1/2=31/15; HISTOLOGY: adenocarcinoma=20, squamous=14, large cell=3, NSCLC=8, adenosquamous=1. A total of 221 cycles have been administered (median number 4.8 for patients). In intent-to-treat analysis, partial response was achieved in 17 patients (36.95%), stable disease and progressive disease was detected in 16 (34.78%) and 10 (21.73%) patients, respectively. Time to progression was 30.9 weeks; median survival time was 42.7 weeks; the survival rates at 12 and 18 months were 34.79 and 15.21%, respectively. No toxic deaths occurred. No patients experienced grade 4 neutropenia and thrombocytopenia. Neutropenia grade 3 occurred in 10 patients (21.7%); Anemia grade 3 in 1 (2.1%); Thrombocytopenia grade 2 in two patients (4.3%) and grade 3 in one (2.1%). Peripheral neuropathy grade 1 occurred in ten (21.7%) and grade 2 in two patients (4.3%). Additional non-haematological toxicities were mild nausea, emesis and fatigue. GIT is well tolerated and active regimen in both advanced and metastatic NSCLC. These data suggest future investigations for GIT schedule as a possible alternative to platinum-based regimens in selected advanced/metastatic NSCLC patients where survival, tolerability and quality of life are the primary goals.