title: A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer.
abstract: BACKGROUND
  Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy.
  
  
  METHODS
  Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion.
  
  
  RESULTS
  Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months.
  
  
  CONCLUSIONS
  Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For further studies, the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2.
authors.affiliation: Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27516, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Center
authors.forename: William Jeffrey
authors.initials: WJ
authors.lastname: Petty
authors.forename: Diandra
authors.initials: D
authors.lastname: Ayala
authors.forename: William H
authors.initials: WH
authors.lastname: Hinson
authors.forename: James
authors.initials: J
authors.lastname: Lovato
authors.forename: James
authors.initials: J
authors.lastname: Capellari
authors.forename: Timothy
authors.initials: T
authors.lastname: Oaks
authors.forename: Antonius A
authors.initials: AA
authors.lastname: Miller
authors.forename: Arthur William
authors.initials: AW
authors.lastname: Blackstock
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D021621:Imaging, Three-Dimensional; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D000077156:Gefitinib