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

BAGKGROUND, The combination of paclitaxel and carboplatin is widely used in the treatment of patients with advanced nonsmall cell lung carcinoma. In t his Phase I/II study the authors evaluated the feasibility, toxicity, and e fficacy of adding a third active antineoplastic agent, gemcitabine, to the paclitaxel/carboplatin combination for the treatment of patients with advan ced nonsmall cell lung carcinoma. METHODS. Patients. with advanced WCC Stage IIIB or IV) nonsmall cell lung c arcinoma previously untreated with chemotherapy were eligible for this tria l. The maximum tolerated doses, determined in the Phase I trial and subsequ ently used in the Phase II trial, were: paclitaxel, 200 mg/m(2), as a 1-hou r infusion on Day 1; carboplatin, at area under the curve dose of 5.0 intra venously (i.v.), on Day 1; and gemcitabine, 1000 mg/m(2) i.v., on Days 1 an d 8. Treatment courses were repeated every 21 days. The Phase II study was conducted in 13 community-based practices in the Minnie Pearl Cancer Resear ch Network; 77 patients were treated between December 1996 and September 19 97. RESULTS. Thirty-four of 77 patients (44%) in the Phase II trial had major r esponses (partial responses, 32 patients and complete responses, 2 patients ). An additional 25 patients (33%) had stable disease or minor response; on ly 23% of patients progressed or were removed from study at or prior to fir st reevaluation. The median survival was 9.4 months, with a 45% actuarial 1 -year survival rate. Myelosuppression was the most common toxicity, with Gr ade 3/4 NCI Common Toxicity Criteria leukopenia and thrombocytopenia in 49% and 45% of patients, respectively. However, only 11 patients (14%) require d hospitalization for neutropenia/ fever, and none had bleeding complicatio ns. Grade 3/4 nonhematologic toxicities included fatigue (41%), arthralgias /myalgias (26%), peripheral neuropathy (8%), nausea/emesis (6%), and hypers ensitivity reactions (4%). There was one treatment-related death due to sep sis. CONCLUSIONS. This three-drug regimen is active and has acceptable toxicity in patients with advanced nonsmall cell lung carcinoma. Myelosuppression, p articularly thrombocytopenia, is increased in comparison to the paclitaxel/ carboplatin regimen. Fatigue also may be increased, but other nonhematologi c toxicities are not altered substantially by adding gemcitabine. Although the response rate and median survival are improved modestly compared with o ur previous experience with paclitaxel/carboplatin, definitive conclusions regarding the efficacy of this regimen await the completion of randomized t rials. Cancer 1999;85:1269-76. (C) 1999 American Cancer Society.