PACLITAXEL AND CARBOPLATIN IN COMBINATION IN THE TREATMENT OF ADVANCED NON-SMALL-CELL LUNG-CANCER - A PHASE-II TOXICITY, RESPONSE, AND SURVIVAL ANALYSIS

Purpose: To determine the activity and toxicity of combination paclitaxel (24 hours) and carboplatin in advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Eligibility required measurable disease (stage IV or stage IIB with malignant pleural effusion), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count greater than or equal to 2,000/mu L, platelet count greater than or equal to 100,000/mu L serum creatinine concentration less than or equal to 1.5 mg/dL, and bilirubin level less than or equal to 2 mg/dL. Paclitaxel was initially administered at a dose of 135 mg/m(2)/d, followed by carboplatin on day 2 at a targeted area under the concentration-time curve (AUG) of 7.5 using the Calvert formula. Granulocyte colony-stimulating factor (G-CSF) 5 mu g/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In patients who sustained less than grade 4 myelosuppression, the paclitaxel dose was sequentially escalated 40 mg/m(2) per cycle to a maximum of 215 mg/m(2). Treatment was repeated at 3-week intervals for six cycles. Results: From June 1993 through February 1994, 54 patients were enrolled; 53 are assessable for toxicity and response. The median age was 62 years (range, 34 to 84). Sixty-nine percent were male, 65% had adenocarcinoma, and 93% had stage IV disease. Two hundred sixty-eight cycles were administered; 32 patients (59%) completed all six cycles. Twenty-five unanticipated hospitalizations occurred during treatment (9.3% of cycles) in 20 patients (37%). Myelosuppression was the principal toxicity; grade 3 or 4 granulocytopenia occurred in 57% of patients after the first cycle, but decreased to 35% during the second cycle after introduction of G-CSP and consistently remained less than or equal to 22% during subsequent cycles. Seven episodes of neutropenic fever occurred, all during the first cycle. Grade 3 or 4 thrombocytopenia and anemia occurred in 47% and 33% of patients, respectively. Eight patients (15%) required platelet transfusions and 16(30%) required packed RBC support. Neuropathy, my algias/arthralgias, and thrombocytopenia, although generally mild, were cumulative. The paclitaxel dose wets boosted to 215 mg/m(2) in greater than or equal to 70% of patients who received three or more cycles. Ar an AUC of 7.5, the median first-cycle carboplatin dose was 424 mg/m(2) (range, 273 to 709 mg/m(2)). The objective response rate was 62%, with five (9%) complete responses and 28 (53%) partial responses. The median progression-free survival time was 28 weeks and the median survival time 53 weeks. The 1-year survival rate is 54%. Conclusion: The paclitaxel-carboplatin combination is active in advanced NSCLC and may enhance survival; it merits further investigation in phase III trials. J Clin Oncol 13:1860-1870. (C) 1995 by American Society of Clinical Oncology.