title: Phase Ia/Ib chemo-radiation trial of gemcitabine and dose-escalated thoracic radiation in patients with stage III A/B non-small cell lung cancer.
abstract: BACKGROUND
  The safety of dose-escalated thoracic radiation concurrent with gemcitabine in patients with inoperable stage III non-small cell lung cancer has not been studied.
  
  
  METHODS
  The maximal tolerated dose of 35 mg/m twice-weekly gemcitabine and concurrent standard thoracic radiation was established in a previous phase Ia trial. In this study, a second patient cohort (phase Ib) received twice-weekly gemcitabine concurrent with three-dimensional dose-escalated thoracic radiation (60-74 Gy) after two cycles of induction chemotherapy: gemcitabine (1000 mg/m) day 1 and 8 and carboplatin (area under the curve 5.0-5.5) day 1 every 21 days.
  
  
  RESULTS
  Twenty-three patients were entered in the phase Ib portion of this trial. Grade III/IV hematologic toxicity was primarily thrombocytopenia (22%) and neutropenia (26%). Grade III/IV esophageal toxicities occurred in 17% of patients, and grade III radiation pneumonitis/dyspnea was observed in 7 of 23 patients. The median and 2-year survival for phase Ib patients were 17.4 months and 32%, respectively. The overall 1- and 2-year survival for all 39 patients (16 phase Ia, 23 phase Ib) was 69% and 32%, respectively.
  
  
  CONCLUSIONS
  Combining 74-Gy thoracic radiation and concurrent gemcitabine is feasible, but the use of this regimen should be limited to the confines of a clinical trial. A randomized phase II trial through the Cancer and Leukemia Group B is underway to further evaluate the efficacy of this regimen.
authors.affiliation: Department of Radiation Oncology, Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina 27516, USA. ablackst@wfubmc.edu
authors.forename: A William
authors.initials: AW
authors.lastname: Blackstock
authors.forename: Coty
authors.initials: C
authors.lastname: Ho
authors.forename: Jerome
authors.initials: J
authors.lastname: Butler
authors.forename: June
authors.initials: J
authors.lastname: Fletcher-Steede
authors.forename: L Douglas
authors.initials: LD
authors.lastname: Case
authors.forename: William
authors.initials: W
authors.lastname: Hinson
authors.forename: Antonius A
authors.initials: AA
authors.lastname: Miller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004947:Esophagus / Q000528:radiation effects; D005260:Female; D005541:Forced Expiratory Volume / Q000528:radiation effects; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D013909:Thorax / Q000528:radiation effects*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine