title: Fractionated scheme of oral vinorelbine as single-agent therapy or in combination with cisplatin concomitantly with thoracic radiotherapy in stage III non-small-cell lung cancer: dose-escalation phase I trial.
abstract: BACKGROUND
  A dose-determination study was conducted in untreated stage III non-small-cell lung cancer to assess continuous exposure to fractionated oral vinorelbine (NVBo), a radiosensitizer, during the radiotherapy period, either alone (first cohort) or in combination with cisplatin (second cohort).
  
  
  METHODS
  Three patients with stage IIIAN2/IIIB were expected at each dose level, with 3 additional patients in case of dose-limiting toxicity (DLT). Concomitantly with a 60-Gy total dose of radiotherapy, NVBo was given from 60 mg up to 180 mg total dose per week split on days 1, 3, and 5. Once the maximum tolerated dose (MTD), defined as 2 DLTs in a dose level, was determined and the recommended dose of NVBo alone was established, the trial assessed its recommended dose in combination with cisplatin 80 mg/m(2) every 3 weeks.
  
  
  RESULTS
  In the first cohort, 26 patients were enrolled. MTD was 160 mg/wk; there were 3 cases of grade 3 esophagitis and 1 of grade 3 pneumonia as DLT out of 5 patients in this dose level. In the recommended dose level (150 mg/wk), only 1 of 6 patients experienced a DLT. In the second cohort, 11 patients received NVBo weekly doses from 130 mg to 150 mg with cisplatin. Only 2 patients received 150 mg/wk NVBo; the trial closed before MTD was determined. The confirmed response rates were 42% and 55% in the first and second cohort, respectively.
  
  
  CONCLUSIONS
  The recommended dose of this fractionated NVBo scheme as single-agent therapy concomitantly with radiotherapy for 6 weeks is 50 mg on days 1, 3, and 5 (150 mg/wk); combined with cisplatin 80 mg/m(2) every 3 weeks, the dose should be 140 to 150 mg/wk adapted on hematology. The response rate is promising.
authors: Oncology Centre-Institute, Warsaw, Poland.
authors: Maciej
authors: M
authors: Krzakowski
authors: Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France. Electronic address: christel.lucas@pierre-fabre.com.
authors: Christel
authors: C
authors: Lucas
authors: S.G. Moscati Hospital, Avellino, Italy.
authors: Cesare
authors: C
authors: Gridelli
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D019583:Dose Fractionation, Radiation; D004941:Esophagitis / Q000209:etiology; D005260:Female; D006801:Humans; D007391:International Cooperation; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Locally advanced; NSCLC; Radiotherapy; Vinorelbine