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Phase I/II Study of Gemcitabine plus Vinorelbine in Non-Small Cell Lung Cancer

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Abstract

Background: Because gemcitabine andvinorelbine have demonstrated single-agentactivity in non-small cell lung cancer(NSCLC), we conducted this phase I/II studyto determine the maximum tolerated dose(MTD) and activity of these drugs combined.

Patients and methods: Patients withinoperable or advanced NSCLC and no priorchemotherapy were treated with gemcitabineplus vinorelbine on days 1 and 8 every 21days. The initial doses of gemcitabine1,000 mg/m2 and vinorelbine25 mg/m2 were escalated by250 mg/m2 and 5 mg/m2,respectively, in separate patient cohortsuntil the MTD was established.

Results: In phase I, 32 patientsreceived a total of 115 cycles. Dose-limiting toxicities were neutropeniaand hepatotoxicity, occurring at the doselevel of 1,500 mg/m2 and30 mg/m2. Thus, the MTD used forphase II was 1,250 mg/m2 and30 mg/m2. Of 41 patients in phase II,16 (39%) achieved objective responses(95% confidence interval [CI] 24% to54%), with a median time to progression of4.2 months. Overall survival was 9 months(95% CI 5.7 to 12.7 months) and the 1-yearsurvival rate was 31%. World HealthOrganization (WHO) ≥grade 3neutropenia and reversible thrombocytosisoccurred in 15% and 65% of patients,respectively. Non-hematologic toxicity wasmild at all dose levels. Grades 3 and 4hepatotoxicity were reported in one patienteach.

Conclusion: The combination of1,250 mg/m2 gemcitabine and30 mg/m2 vinorelbine on days 1 and 8every 21 days is well tolerated and activein patients with NSCLC. These resultsshould be confirmed in comparativestudies.

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Authors and Affiliations

  1. Medical Oncology Department, Hospital Central de Asturias, Oviedo, Spain

    Emilio Esteban, Joaquin Fra, Norberto Corral, Miguel Valle, Juan Carrasco, Marian Sala, Javier Puerta, Enrique Estrada, Isabel Palacio, Jose Maria Vieitez, Jose Maria Buesa & Angel Jimenez Lacave

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  1. Emilio Esteban
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  2. Joaquin Fra
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  3. Norberto Corral
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  4. Miguel Valle
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Esteban, E., Fra, J., Corral, N. et al. Phase I/II Study of Gemcitabine plus Vinorelbine in Non-Small Cell Lung Cancer. Invest New Drugs 20, 73–82 (2002). https://doi.org/10.1023/A:1014490417342

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