Randomised multicenter phase II study of two schedules of docetaxel and gemcitabine or cisplatin/gemcitabine followed by docetaxel as first line treatment for advanced non-small cell lung cancer

Background: In the attempt to optimize the efficacy of chemotherapy in advanced non-small cell lung cancer (NSCLC) several strategies need to be investigated including the use of non-platinum combinations and the sequential use of different agents. Patients and methods: In a phase II randomised study 165 patients with stage IIIB or IV NSCLC were assigned to receive docetaxel 40 mg/m² days 1 and 8 plus gemcitabine 1200 mg/m² days 1 and 8 every 21 days (arm A, N = 54) or docetaxel 50 mg/m² days 1 and 15 plus gemcitabine 1600 mg/m² days 1 and 15 every 28 days (arm B, N = 57) or gemcitabine 1200 mg/m² days 1 and 8 plus cisplatin 100 mg/m² day 2 every 21 days for 3 cycles followed by docetaxel 75 mg/m² day 1 every 21 days for 3 cycles (arm C, N = 54). The primary endpoint of the trial was overall response rate. Secondary end points included safety, progression-free and overall survival. Results: Response rate was 22.2%, 23.2% and 33.3% after 3 cycles, whereas at the end of treatment was 24.1%, 12.5% and 27.8% in arm A-C, respectively. Median time to progression was similar in all the 3 arms: 6.7 months in arm A (95% CI: 4.8-9.7), 5.6 in arm B (5.0-7.9) and 6.6 in arm C (5.7-9.1). The median survival time was 10.7 months in arm A (95% CI: 6.8-15.6), 8.9 in arm B (7.4-12.5) and 14.6 in arm C (8.0-22.4) and 1-year survival rate was 46.3%, 37.9% and 53.9%, respectively. Grade 3-4 haematological toxicities were more frequent in arm C while non-haematological were more common in the gemcitabine and docetaxel arms. Conclusions: The results of this phase II randomised clinical trial do not indicate a clear superior efficacy of one of the tested combinations according to the planned statistical design and none of these regimens is sufficiently active or less toxic to warrant further investigation in a phase III study.