Phase I/II trial of paclitaxel by 1-hour infusion, carboplatin, and gemcitabine in the treatment of patients with advanced nonsmall cell lung carcinoma.

Abstract

The combination of paclitaxel and carboplatin is widely used in the treatment of patients with advanced nonsmall cell lung carcinoma. In this Phase I/II study the authors evaluated the feasibility, toxicity, and efficacy of adding a third active antineoplastic agent, gemcitabine, to the paclitaxel/carboplatin combination for the treatment of patients with advanced nonsmall cell lung carcinoma. Patients with advanced (AJCC Stage IIIB or IV) nonsmall cell lung carcinoma previously untreated with chemotherapy were eligible for this trial. The maximum tolerated doses, determined in the Phase I trial and subsequently used in the Phase II trial, were: paclitaxel, 200 mg/m2, as a 1-hour infusion on Day 1; carboplatin, at area under the curve dose of 5.0 intravenously (i.v.), on Day 1; and gemcitabine, 1000 mg/m2 i.v., on Days 1 and 8. Treatment courses were repeated every 21 days. The Phase II study was conducted in 13 community-based practices in the Minnie Pearl Cancer Research Network; 77 patients were treated between December 1996 and September 1997. Thirty-four of 77 patients (44%) in the Phase II trial had major responses (partial responses, 32 patients and complete responses, 2 patients). An additional 25 patients (33%) had stable disease or minor response; only 23% of patients progressed or were removed from study at or prior to first reevaluation. The median survival was 9.4 months, with a 45% actuarial 1-year survival rate. Myelosuppression was the most common toxicity, with Grade 3/4 NCI Common Toxicity Criteria leukopenia and thrombocytopenia in 49% and 45% of patients, respectively. However, only 11 patients (14%) required hospitalization for neutropenia/ fever, and none had bleeding complications. Grade 3/4 nonhematologic toxicities included fatigue (41%), arthralgias/myalgias (26%), peripheral neuropathy (8%), nausea/emesis (6%), and hypersensitivity reactions (4%). There was one treatment-related death due to sepsis. This three-drug regimen is active and has acceptable toxicity in patients with advanced nonsmall cell lung carcinoma. Myelosuppression, particularly thrombocytopenia, is increased in comparison to the paclitaxel/carboplatin regimen. Fatigue also may be increased, but other nonhematologic toxicities are not altered substantially by adding gemcitabine. Although the response rate and median survival are improved modestly compared with our previous experience with paclitaxel/carboplatin, definitive conclusions regarding the efficacy of this regimen await the completion of randomized trials.