A PHASE I-II STUDY OF PACLITAXEL, IFOSFAMIDE, AND VINORELBINE WITH FILGRASTIM (RHG-CSF) SUPPORT IN ADVANCED NON-SMALL-CELL LUNG-CANCER

Purpose. We designed a phase I-II trial of three active agents, paclit axel, ifosfamide, and vinorelbine, in advanced non-small-cell lung can cer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maxim um tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support, and 2) determine the overall response rate and median survival of pat ients treated on this regimen. Patients and methods. We treated cohort s of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m( 2)/day x 3 and vinorelbine 20-25 mg/m(2)/day x 3 and escalating doses of paclitaxel at 100-175 mg/m(2) on day 2 with G-CSF support on a 21-d ay cycle. One prior experimental single-agent chemotherapy regimen was allowed. Results. Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recom mended phase II dose (RPTD). Thirteen patients had received prior chem otherapy, Paclitaxel doses of 175 mg/m(2) and 150 mg/m(2) produced dos e-limiting myelosuppression, and the RPTD was determined to be paclita xel 135 mg/m(2) with ifosfamide 1.2 g/m(2)/day on days 1-3 and vinorel bine 20 mg/m(2)/ day on days 1-3 with G-CSF support. The overall respo nse rate was 18%, with a median survival of 6.1 months. Six of 35 pati ents (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. Conclusions. This n on-cisplatin-containing three-drug regimen has substantial toxicity an d low activity in advanced NSCLC, and does not seem to improve on prio r regimens. It is unclear whether the lack of efficacy relates to an a ntagonistic reaction between the specific drugs, administration schedu le, or to subtherapeutic doses of the individual agents.