Phase II study of vinorelbine and gemcitabine for inoperable stage IIIB-IVnon-small-cell lung cancer

Purpose: To evaluate the efficacy of the combination of vinorelbine and gem citabine as a non-platinum chemotherapy regimen in patients with inoperable locally-advanced or metastatic non-small-cell lung cancer (NSCLC). Efficac y was assessed primarily in terms of response rate, and secondarily in term s of toxicity, time to progression and survival. Patients and methods: Patients with cytologically- or histologically-proven stage IIIB-IV NSCLC, bi-dimensionally measurable lesions, adequate haemato logical, hepatic and renal function, WHO performance status less than or eq ual to 2 and no previous chemotherapy or radiotherapy were eligible. The fi rst 12 patients were entered in a pilot study and received vinorelbine (VNR ) 30 mg/m(2) on days 1, 8, 15 and 22, and gemcitabine (GEM) 1000 mg/m(2) on days 1, 8 and 15, of a 28-day cycle. Subsequently, patients were entered i n a phase II trial of VNR 35 mg/m(2) and GEM 1200 mg/m(2) on days 1 and 15 of each 28-day cycle. Treatment consisted of three cycles of the chemothera py, with a further three cycles for those patients who achieved stable dise ase or a complete or partial response (CR/PR) to the first three cycles. Pa tients who had achieved CR or PR after six cycles continued with the treatm ent until relapse. Results: The dosage and scheduling of VNR and GEM in the pilot study result ed in neutropenia necessitating reductions or delays in treatment, and cons equently low dose intensity. The schedule was thus modified to VNR 35 mg/m( 2) and GEM 1200 mg/m(2) on days 1 and 15 of each 28-day cycle for the phase II trial. Thirty-three patients were enrolled in the phase II trial, and 2 8 were evaluable for response. The overall intent-to-treat response rate of all 45 patients was 40% (18 of 45), comprising 4 CR (9%) and 14 PR (31%). For the 28 evaluable patients who received the fortnightly chemotherapy the response rate was 46% (13 of 28), CR 11% (3 of 28) and PR 36% (10 of 28). Seven patients (25%) had stable disease. The one-year cumulative survival r ate for the 33 patients receiving the fortnightly chemotherapy was 24% and median time-to-progression 4 months (range 1-16 months). Median survival fo r these patients was eight months. Nine out of twelve patients in the pilot study (75%) suffered grade 3-4 neutropenia. There was one toxic death, att ributed to neutropenic fever and sepsis, and two cases of pulmonary embolis m. One patient suffered Grade 4 thrombocytopenia. Only eight patients (24%) on the fortnightly schedule suffered grade 3-4 neutropenia, resulting in d ose reductions or delays for three of them (9%). None of the patients on th e fortnightly schedule suffered thrombocytopenia or anaemia. Conclusions: The fortnightly schedule of gemcitabine and vinorelbine was a well-tolerated out-patient regimen, producing response and survival rates c omparable to those of cisplatin combination regimens, but with a more favou rable toxicity profile. Gemcitabine and vinorelbine should now be tested in a triplet combination with a taxane as the third drug, or against a platin um-containing regimen in a phase III study.