A Pilot Trial of Gemcitabine and Vinorelbine Plus Capecitabine in Locally Advanced or Metastatic Nonsmall Cell Lung Cancer:

Objectives: We conducted a pilot study of gemicitabine, vinorelbine and capecitabine combination to evaluate its toxicity and efficacy in chemo-naive patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) after a short phase IB trial. Methods: Eligible chemo-naive patients with stage IIIB or IV NSCLC received Outpatient administration of gemcitabine 900 mg/m(2) and vinorelbine 25 mg/m(2) intravenously on days I and 8, every 3 weeks, concurrently with capecitabine 1000 mg/m(2) give,, orally twice a day on days 1 to 5 and 8 to 12 (dose level I), or days 1 to 6 and 8 to 13 (dose level II). Results: Between November 2002 and December 2003, 19 patients participated in the study at either dose level 1 (7 patients) or dose level II (12 patients). The maximum tolerated dose, defined as the dose at which no more than 1 of 6 patients in a cohort experienced a dose-limiting toxicity (DLT) in the first cycle, was not established. However, 1 of 7 patients at dose level 1, and 2 of 12 at dose level II experienced DLTs (ie, grade 3 hepatotoxicity in 2 patients, and grade 3 febrile neutropenia in 1 patient). In addition, 2 patients experienced treatment-related pneumonitis requiring mechanical ventilator support after the second course of therapy. Objective tumor response was observed in 5 (26.3%) of 19 patients. Further patient accrual was stopped according to the Study design. Conclusions: This 3-drug combination showed disappointing anti-tumor activity against NSCLC with unexpected life-threatening pulmonary toxicity. No further investigation of this regimen is recommended for patients with NSCLC.