title: Activity and toxicity of gemcitabine and gemcitabine + vinorelbine in advanced non-small-cell lung cancer elderly patients: Phase II data from the Multicenter Italian Lung Cancer in the Elderly Study (MILES) randomized trial.
abstract: BACKGROUND
  Following the demonstration that vinorelbine improves survival and quality of life compared with best supportive care in elderly patients with advanced non-small-cell lung cancer (NSCLC), we started the three-arm prospective Multicenter Italian Lung Cancer in the Elderly Study (MILES) trial of vinorelbine, gemcitabine and gemcitabine + vinorelbine.
  
  
  METHODS
  Within the randomized phase 3 trial, pilot single-stage phase 2 studies were planned for gemcitabine and for gemcitabine + vinorelbine. Eligible patients are aged 70 or more, with stage IV or IIIb (with metastatic supraclavear nodes or malignant pleural effusion) NSCLC. Single-agent gemcitabine is given at 1200 mg/m(2) on days 1 and 8; in the combination, gemcitabine is given at 1000 mg/m(2) and vinorelbine at 25 mg/m(2), both on days 1 and 8, every 3 weeks.
  
  
  RESULTS
  As planned 49 patients were enrolled in each group. Median age was 74 in both groups. Two-thirds of patients had stage IV disease. The response rate was 18.4% (95% exact CI 8.8-32.0) with both treatments. With single-agent gemcitabine main toxicities were grade 4 thrombocytopenia and grade 2 hepatic toxicity, in one patient each, and grade 2 pulmonary toxicity in two patients. With gemcitabine + vinorelbine combination there were grade 4 neutropenia and thrombocytopenia (one patient each), grade 3 anemia requiring red blood cell transfusion (two patients), and grade 4 fever in two patients. Four patients, with severe cardiac comorbidities, suffered grade 3 heart toxicity with atrial flutter or fibrillation, followed by congestive heart failure responsive to treatment.
  
  
  CONCLUSIONS
  Both single-agent gemcitabine and the gemcitabine + vinorelbine combination are sufficiently active and tolerable to allow continuation of the MILES study.
authors.affiliation: Divisione di Oncologioca Medica B, Istituto Nazionale per lo Studio e la Cura dei Tumori, via M. Semmola, 80131 Naples, Italy. cgridelli@sirio-oncology.it
authors.forename: C
authors.initials: C
authors.lastname: Gridelli
authors.forename: S
authors.initials: S
authors.lastname: Cigolari
authors.forename: C
authors.initials: C
authors.lastname: Gallo
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: G P
authors.initials: GP
authors.lastname: Ianniello
authors.forename: L
authors.initials: L
authors.lastname: Frontini
authors.forename: F
authors.initials: F
authors.lastname: Ferraù
authors.forename: S F
authors.initials: SF
authors.lastname: Robbiati
authors.forename: V
authors.initials: V
authors.lastname: Adamo
authors.forename: G
authors.initials: G
authors.lastname: Gasparini
authors.forename: S
authors.initials: S
authors.lastname: Novello
authors.forename: F
authors.initials: F
authors.lastname: Perrone
mesh_terms: D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000139:chemically induced; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine