title: Continuous-infusion vinorelbine for the treatment of advanced non-small-cell lung cancer: a phase I/II study.
abstract: BACKGROUND
  In this phase I/II trial, the maximum tolerated dose (MTD) and activity of vinorelbine administered in continuous infusion as first-line treatment for advanced non-small-cell lung cancer (NSCLC) was determined in 25 consecutive chemotherapy-naive patients with advanced NSCLC.
  
  
  METHODS
  Vinorelbine was administered as an initial intravenous (I.V.) bolus of 8 mg/m(2) on day 1 followed by a 4-day continuous I.V. infusion at 5 different 24-hour dose levels to be repeated every 21 days. All 25 patients (159 cycles) were evaluable for response. The MTD was 8 mg/m(2) bolus followed by a continuous I.V. infusion of 11 mg/m(2) per day over 4 days.
  
  
  RESULTS
  The dose-limiting toxicities were febrile neutropenia in 6 patients and grade 3 mucositis in 2 patients. There was less neurotoxicity and constipation and more mucositis compared with the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Treatment responses were observed in 6 patients: 1 complete response and 5 partial responses. The overall response rate was 24% (95% confidence interval [CI], 8%-40%). Median time to progression was 4 months (95% CI, 2-11 months), and median survival was 6 months (95% CI, 2-18 months).
  
  
  CONCLUSIONS
  The results demonstrate that, in this setting of first-line treatment of NSCLC, vinorelbine administered as an 8 mg/m(2) bolus followed by a continuous infusion of 11 mg/m(2) per day over 4 days is the recommended schedule. Further trials are necessary to establish activity and possible benefits of combination with other agents.
authors.affiliation: Department of Medical Oncology, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Carabante-Ocón
authors.forename: Manuel
authors.initials: M
authors.lastname: Cobo-Dols
authors.forename: Manuel
authors.initials: M
authors.lastname: Benavides-Orgaz
authors.forename: Silvia
authors.initials: S
authors.lastname: Gil-Calle
authors.forename: Immaculada
authors.initials: I
authors.lastname: Alés-Díaz
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Bretón-García
authors.forename: Esther
authors.initials: E
authors.lastname: Villar-Chamorro
authors.forename: Alvaro
authors.initials: A
authors.lastname: Montesa-Pino
authors.forename: Julia
authors.initials: J
authors.lastname: Alcalde-García
authors.forename: Vanesa
authors.initials: V
authors.lastname: Gutiérrez-Calderón
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D001247:Asthenia / Q000139:chemically induced; D018287:Carcinoma, Large Cell / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine