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Background: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations.Patients and methods: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m2 and VNR 25 mg/m2 on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m2 and PTX 125 mg/m2 on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m2 on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m2 on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles.Results: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens.Conclusions: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile. [ABSTRACT FROM AUTHOR]

Background: We evaluated safety and efficacy of PTK787/ZK222584 (PTK/ZK), a novel tyrosine kinase inhibitor of KIT, platelet-derived growth factor receptors and vascular endothelial cell growth factor receptors (VEGFRs), in patients with imatinib-resistant gastrointestinal stromal tumor (GIST). This is the first study of PTK/ZK in this population. Patients and methods: Patients with metastatic GIST that had progressed after ≥ 4-week treatment with imatinib mesylate were eligible. Prior VEGFR-2 inhibitor therapy was not permitted. PTK/ZK 1250 mg orally once-daily was administered to 15 patients (accrued as a two-stage procedure), most of whom (n = 11) had been unsuccessfully treated with imatinib 800 mg daily, until treatment failure. Patients were monitored at 4- to 8-week intervals. Results: All 15 patients enrolled were eligible; two (13%) achieved partial response (PR), eight (53%) had stable disease (SD) ≥3 months, and five (33%) progressed. The clinical benefit rate (PR + SD) was 67% (95% CI 38% to 86%). Median time to progression was 8.5 months (range 0.9–24.8+ months). Three patients had not progressed at the time of analysis, including one PR at 24.8 months and two SDs at 16.6 and 18.6 months on treatment. PTK/ZK was generally well tolerated. Conclusion: PTK/ZK 1250 mg p.o. once daily is active and well tolerated in patients with imatinib-resistant GIST. [ABSTRACT FROM AUTHOR]