title: Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT.
  
  
  METHODS
  Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT.
  
  
  RESULTS
  A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6).
  
  
  CONCLUSIONS
  Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina. Electronic address: christopher.kelsey@duke.edu.
authors.forename: Chris R
authors.initials: CR
authors.lastname: Kelsey
authors.affiliation: Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Shiva
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Dunphy
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Neal E
authors.initials: NE
authors.lastname: Ready
authors.affiliation: Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Marks
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D004947:Esophagus / Q000528:radiation effects; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006321:Heart / Q000528:radiation effects; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D059351:Organ Sparing Treatments; D011788:Quality of Life; D011832:Radiation Injuries / Q000473:pathology; D061089:Radiotherapy, Image-Guided / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D005047:Etoposide; D002945:Cisplatin