title: Phase I/II study of gemcitabine plus vinorelbine in non-small cell lung cancer.
abstract: BACKGROUND
  Because gemcitabine and vinorelbine have demonstrated single-agent activity in non-small cell lung cancer (NSCLC), we conducted this phase I/II study to determine the maximum tolerated dose (MTD) and activity of these drugs combined.
  
  
  METHODS
  Patients with inoperable or advanced NSCLC and no prior chemotherapy were treated with gemcitabine plus vinorelbine on days 1 and 8 every 21 days. The initial doses of gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 were escalated by 250 mg/m2 and 5 mg/m2, respectively, in separate patient cohorts until the MTD was established.
  
  
  RESULTS
  In phase I, 32 patients received a total of 115 cycles. Dose-limiting toxicities were neutropenia and hepatotoxicity, occurring at the dose level of 1,500 mg/m2 and 30 mg/m2. Thus, the MTD used for phase II was 1,250 mg/m2 and 30 mg/m2. Of 41 patients in phase II, 16 (39%) achieved objective responses (95% confidence interval [CI] 24% to 54%), with a median time to progression of 4.2 months. Overall survival was 9 months (95% CI 5.7 to 12.7 months) and the 1-year survival rate was 31%. World Health Organization (WHO) > or = grade 3 neutropenia and reversible thrombocytosis occurred in 15% and 65% of patients, respectively. Non-hematologic toxicity was mild at all dose levels. Grades 3 and 4 hepatotoxicity were reported in one patient each.
  
  
  CONCLUSIONS
  The combination of 1,250 mg/m2 gemcitabine and 30 mg/m2 vinorelbine on days 1 and 8 every 21 days is well tolerated and active in patients with NSCLC. These results should be confirmed in comparative studies.
authors: Medical Oncology Department, Hospital Central de Asturias, Oviedo, Spain. emilioes@ene.es
authors: Emilio
authors: E
authors: Esteban
authors: Joaquin
authors: J
authors: Fra
authors: Norberto
authors: N
authors: Corral
authors: Miguel
authors: M
authors: Valle
authors: Juan
authors: J
authors: Carrasco
authors: Marian
authors: M
authors: Sala
authors: Javier
authors: J
authors: Puerta
authors: Enrique
authors: E
authors: Estrada
authors: Isabel
authors: I
authors: Palacio
authors: Jose Maria
authors: JM
authors: Vieitez
authors: Jose Maria
authors: JM
authors: Buesa
authors: Angel Jimenez
authors: AJ
authors: Lacave
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine