Paclitaxel and carboplatin in combination with gemcitabine: A phase I-II trial in patients with advanced non-small-cell lung cancer

Background: The combination of paclitaxel (P) and carboplatin (C) is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active new drug. We planned a phase I study to find the maximum tolerated dose (MTD) of the PCG combination. A phase II study was subsequently conducted to evaluate the activity and toxicity of PCG. Patients and methods: Forty-five patients entered the study. Twenty-eight had stage IIIA-B disease, 17 stage IV. In the phase I study, with a fixed dose of C at AUC = 6 on day 1, P was escalated using increments of 25 mg/m(2) starting from 175 mg/m(2) on day 1 and G with increments of 200 mg/m(2) starting from 800 mg/m(2) on day 1 and 8. Results: Fourteen patients entered the phase I study. The MTD was reached at P 200 mg/m(2), C AUC = 6 and G 1000 mg/m(2). Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities. Thirty-one patients were treated in the phase II study with P 175 mg/m(2), C AUC = 6 and G 1000 mg/m(2). Response rate was 57% (68% in stage III and 47% in stage IV). Myelosuppression was the main toxicity, with grade 3-4 leukopenia occurring in 35% of cases. Grade 3 anemia was observed in 24% of cases and grade 3-4 thrombocytopenia occurred in 34% of patients. Non-hematological toxicity was mild. Median survival and one-year actuarial survival were 20.5 months and 74% for stage III and 11.5 months and 47% for stage IV. Conclusions: PCG is a promising regimen for treating advanced NSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin in advanced NSCLC is ongoing. On the other hand, we are planning to introduce the PCG regimen in the treatment of stage II-III patients in the setting of a multimodality treatment.