PACLITAXEL BY 96-HOUR CONTINUOUS-INFUSION IN COMBINATION WITH CISPLATIN - A PHASE-I TRIAL IN PATIENTS WITH ADVANCED LUNG-CANCER

Purpose: To determine the maximum-tolerated dose (MTD) of paclitaxel a dministered by 96-hour continuous infusion in combination with cisplat in, to determine if the addition of granulocyte colony-stimulating fac tor (G-CSF) permits significant paclitaxel dose escalation, and to ass ess the toxicity and preliminary activity of this combination in patie nts with advanced lung cancer. Patients and Methods: Fifty patients wi th untreated lung cancer were enrolled: 42 had advanced non-small-cell lung cancer (NSCLC) and eight had extensive-stage small-cell lung can cer (SCLC). patients received paclitaxel doses of 100 to 180 mg/m(2)/9 6 hours and cisplatin doses of 60 to 80 mg/m(2) as a single 30-minute bolus injection at the end of the paclitaxel infusion. Results: Two of six patients experienced dose-limiting neutropenia at a dose of pacli taxel 140 mg/m(2)/96 hours and cisplatin 80 mg/m(2). With G-CSF suppor t, one of three patients experienced both dose-limiting mucositis and fatal neutropenic sepsis at a dose of paclitaxel 180 mg/m(2)/96 hours and cisplatin 80 mg/m(2). Significant peripheral neuropathy developed in five patients and occurred after six or more cycles of therapy. Thi rty-three of 42 patients with NSCLC had measurable disease; the object ive response rate was 55%, with two complete responses and 16 partial responses. For all 42 patients with NSCLC, the median time to progress ion and median survival duration were 5 months and 10 months, respecti vely. The actuarial 1-year survival rate was 41%. Of eight SCLC patien ts, four responded to therapy, and the median survival duration for al l SCLC patients was 11 months. Conclusion: The MTD without G-CSF is pa clitaxel 120 mg/m(2)/96 hours and cisplatin 80 mg/m(2), and the MTD wi th G-CSF is paclitaxel 160 mg/m(2)/96 hours and cisplatin 80 mg/m(2). Infusional paclitaxel with cisplatin is well tolerated and active in p atients with advanced NSCLC. (C) 1997 by Society of Clinical Oncology.