title: Unfavorable therapeutic index of cisplatin/gemcitabine/vinorelbine in advanced non-small-cell lung cancer.
abstract: In view of favorable reports with the 3-drug combination of PGV (cisplatin/gemcitabine/vinorelbine), this multicenter phase II study evaluated the therapeutic index of PGV in patients with advanced non-small-cell lung cancer (NSCLC). Thirty-two patients with stage IV NSCLC and 1 with stage IIIB were studied. There were 23 men and 10 women, with a median age of 63 years (range, 38-80 years). Twelve patients had a performance status (PS) of 0, and 21 patients had a PS of 1. Treatment consisted of cisplatin 50 mg/m2, gemcitabine 1000 mg/m2, and vinorelbine 25 mg/m2 all given intravenously on days 1 and 8, in 21-day cycles. Fifteen patients (45%; 95% confidence interval (CI), 28%-64%) achieved a partial response. Median response duration was 3 months (range, 1-9 months). The median and 1-year survival rates were 9.4 months and 39% (95% CI, 23%-58%), respectively. The median number of cycles was 4. Only 3 patients (9%) completed treatment without regimen modifications. Median dose intensity (% planned) was cisplatin 24 mg/m2/week (72%), gemcitabine 483 mg/m2/week (72%), and vinorelbine 12 mg/m2/week (72%). Toxicities were predominantly hematologic, with grade 3/4 neutropenia (67%), febrile neutropenia (21%), and thrombocytopenia (67%). There were 3 (9%) treatment-related deaths due to neutropenic complications. This study confirms the substantial antineoplastic activity of PGV. We observed a high rate of severe hematologic toxicity, especially febrile neutropenia, despite a lower delivered dose intensity of PGV. Given these results, PGV appears to offer no therapeutic advantage to current doublet regimens.
authors.affiliation: Division of Hematology/Oncology, St. Elizabeth's Medical Center, Boston, MA 02135, USA. phesketh@massmed.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hesketh
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nauman
authors.forename: Ann M
authors.initials: AM
authors.lastname: Hesketh
authors.forename: Janet
authors.initials: J
authors.lastname: LaPointe
authors.forename: Katrina
authors.initials: K
authors.lastname: Fogarty
authors.forename: Thein H
authors.initials: TH
authors.lastname: Oo
authors.forename: Derick H M
authors.initials: DH
authors.lastname: Lau
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara