title: Phase I/II study of escalating doses of vinorelbine in combination with oxaliplatin in patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Oxaliplatin is a platinum compound active in non-small-cell lung cancer (NSCLC) patients, and vinorelbine (VNB) is an active reference agent. This phase I/II study was performed to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the recommended dose (RD) of a VNB/oxaliplatin combination given to previously untreated patients with advanced NSCLC.
  
  
  METHODS
  Oxaliplatin was given at the fixed dose of 130 mg/m2 (2-hour intravenous [IV] infusion) on day 1. VNB was administered on days 1 and 8 (10-minute IV infusion), with doses starting at 22 mg/m2/d and escalated by 2 mg/m2 increments until MTD. Treatment was repeated every 3 weeks. No special hydration measures or prophylactic granulocyte colony-stimulating factors were used.
  
  
  RESULTS
  Twenty-seven patients (20 men, 7 women) received 110 cycles total at six different VNB dose levels. Neutropenia was the DLT. Although no patient experienced DLT at the highest dose level (32 mg/m2/d), multiple treatment delays (54% of cycles) and dose reductions (34% of cycles) were required at this dose level. Others toxicities were mainly limited to grade 1 peripheral neuropathy and grade 1/2 nausea/vomiting. The relative dose-intensity of administered VNB from dose levels 3 to 6 (26 to 32 mg/m2) remained stable, whereas grade 3/4 neutropenia increased. All patients were assessable for activity; there were 10 objective responses, including one complete response (37% response rate).
  
  
  CONCLUSIONS
  The present combination can be safely administered in an outpatient setting. The RD is VNB 26 mg/m2 days 1 and 8 with oxaliplatin 130 mg/m2 day 1 every 3 weeks.
authors.affiliation: Centre Hospitalier Intercommunal, Créteil, France.
authors.forename: I
authors.initials: I
authors.lastname: Monnet
authors.forename: P
authors.initials: P
authors.lastname: Soulié
authors.forename: H
authors.initials: H
authors.lastname: de Cremoux
authors.forename: S
authors.initials: S
authors.lastname: Saltiel-Voisin
authors.forename: M
authors.initials: M
authors.lastname: Bekradda
authors.forename: J C
authors.initials: JC
authors.lastname: Saltiel
authors.forename: E
authors.initials: E
authors.lastname: Brain
authors.forename: G
authors.initials: G
authors.lastname: Dupont-André
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012074:Remission Induction; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D014747:Vinblastine; D000077235:Vinorelbine