title: Phase I study of vinorelbine, cisplatin, and concomitant thoracic radiation in the treatment of advanced chest malignancies.
abstract: OBJECTIVE
  The cisplatin-vinorelbine regimen has superior activity in advanced non-small-cell lung cancer (NSCLC). We conducted a phase I trial to identify the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of this regimen with concomitant thoracic radiation (RT) in patients with advanced chest malignancies.
  
  
  METHODS
  Patients with advanced chest malignancies that required RT were enrolled onto this phase I study of standard chest radiation (30 daily 2-Gy fractions for a total of 60 Gy) and concurrent chemotherapy with cisplatin starting at 100 mg/m2 every 3 weeks and vinorelbine starting at 20 mg/m2/wk.
  
  
  RESULTS
  Thirty-seven patients were treated on this study. Two of three patients treated at the maximum-administered dose of cisplatin 100 mg/m2 per cycle and vinorelbine 25 mg/m2/wk experienced acute DLT (neutropenia), which required deescalation. The dose level of cisplatin 100 mg/m2 and vinorelbine 20 mg/m2/wk, although tolerated acutely, produced delayed esophagitis, which proved dose-limiting. The recommended phase II dose was cisplatin 80 mg/m2 every 3 weeks and vinorelbine 15 mg/m2 given 2 of every 3 weeks with concomitant chest RT.
  
  
  CONCLUSIONS
  Concomitant chemoradiotherapy with cisplatin and vinorelbine is feasible. The recommended phase II dose is cisplatin 80 mg/m2 every 3 weeks with vinorelbine 15 mg/m2 given twice over 3 weeks on a day 1/day 8 schedule. Esophagitis is the DLT, with neutropenia occurring at higher dose levels. A Cancer and Leukemia Group B (CALGB) phase II trial is currently underway to evaluate further the efficacy and toxicities of this regimen in unresectable stage III NSCLC.
authors.affiliation: Department of Medicine, University of Chicago Medical Center, IL, USA. g-masters@nwu.edu
authors.forename: G A
authors.initials: GA
authors.lastname: Masters
authors.forename: D J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: P C
authors.initials: PC
authors.lastname: Hoffman
authors.forename: L C
authors.initials: LC
authors.lastname: Drinkard
authors.forename: S A
authors.initials: SA
authors.lastname: Krauss
authors.forename: M K
authors.initials: MK
authors.lastname: Ferguson
authors.forename: J
authors.initials: J
authors.lastname: Olak
authors.forename: B L
authors.initials: BL
authors.lastname: Samuels
authors.forename: H M
authors.initials: HM
authors.lastname: Golomb
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D018450:Disease Progression; D004941:Esophagitis / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D015996:Survival Rate; D013899:Thoracic Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine