Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma

Abstract

BACKGROUNDThe authors compared gemcitabine and carboplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) or mitomycin, vinblastine, and cisplatin (MVP) in patients with advanced nonsmall cell lung carcinoma (NSCLC). The primary objective was survival. Secondary objectives were time to disease progression, response rates, evaluation of toxicity, disease‐related symptoms, World Health Organization performance status (PS), and quality of life (QoL).METHODSThree hundred seventy‐two chemotherapy‐naïve patients with International Staging System Stage III/IV NSCLC who were ineligible for curative radiotherapy or surgery were randomized to receive either 4 cycles of gemcitabine (1000 mg/m2 on Days 1, 8, and 15) plus carboplatin (area under the serum concentration‐time curve, 5; given on Day 1) every 4 weeks (the GC arm) or MIC/MVP every 3 weeks (the MIC/MVP arm).RESULTSThere was no significant difference in median survival (248 days in the MIC/MVP arm vs. 236 days in the GC arm) or time to progression (225 days in the MIC/MVP arm vs. 218 days in the GC arm) between the 2 treatment arms. The 2‐year survival rate was 11.8% in the MIC/MVP arm and 6.9% in the GC arm. The 1‐year survival rate was 32.5% in the MIC/MVP arm and 33.2% in the GC arm. In the MIC/MVP arm, 33% of patients responded (4 complete responses [CRs] and 57 partial responses [PRs]) whereas in the GC arm, 30% of patients responded (3 CRs and 54 PRs). Nonhematologic toxicity was comparable for patients with Grade 3–4 symptoms, except there was more alopecia among patients in the MIC/MVP arm. GC appeared to produce more hematologic toxicity and necessitated more transfusions. There was no difference in performance status, disease‐related symptoms, or QoL between patients in the two treatment arms. Fewer inpatient stays for complications were required with GC.CONCLUSIONSThe results of the current study failed to demonstrate any difference in efficacy between the newer regimen of GC and the older regimens of MIC and MVP. Cancer 2003;98:542–53. © 2003 American Cancer Society.DOI 10.1002/cncr.11535

Gemcitabine Plus Carboplatin Versus Mitomycin, Ifosfamide, and Cisplatin in Patients With Stage IIIB or IV Non-Small-Cell Lung Cancer: A Phase III Randomized Study of the London Lung Cancer Group

“…24 A randomized comparison of a 4-week regimen of gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 plus carboplatin AUC 5 on day 1 with either MIC or mitomycin, vinblastine, and cisplatin (MVP) found no significant survival difference, although QOL tended to favor GCa. 25 It is possible that the survival advantage demonstrated for GCa in our study may relate to the use of a 3-week rather than 4-week schedule. The 3-week schedule confers a higher dose-intensity for carboplatin and leads less frequently to grade 3 to 4 thrombocytopenia and hence fewer gemcitabine omissions.…”

Combination phase I study of nedaplatin and gemcitabine for advanced non-small-cell lung cancer

“…More recently, the combination of carboplatin with gemcitabine has become attractive as a therapy for advanced NSCLC. Some randomised studies have indicated that carboplatin -gemcitabine regimen offers equivalent median survival compared with cisplatin -gemcitabine or mitomycin -vinblastine -cisplatin /mitomycin -ifosfamide -cisplatin (Danson et al, 2003;Zatloukal et al, 2003), and results in significant improvements in overall survival over those for gemcitabine alone or the older cisplatin-containing regimens (Grigorescu et al, 2002;Rudd et al, 2002;Sederholm, 2002). However, neutropenia and thrombocytopenia were more common in carboplatin -gemcitabine regimens than others; thrombocytopenia was particularly common.…”

A Randomized Phase II Study Comparing Two Schedules of the 21-Day Regimen of Gemcitabine and Carboplatin in Advanced Non-Small Cell Lung Cancer

“…This regimen is well tolerated, but clinicians frequently have to deal with grade 3–4 neutropenia and grade 3–4 thrombocytopenia. Even though severe bleeding problems are not seen very often, physicians feel uncomfortable about thrombocytopenia because it necessitates more attention, repeated platelet count controls, dose reductions and platelet transfusions [11]. The Norwegian Lung Cancer Study Group recently also reported on a grade 3 thrombocytopenia of 25% and grade 4 thrombocytopenia of 19% in the carboplatin day 1-gemcitabine regimen, resulting in more frequent platelet transfusions and higher costs [12].…”