title: Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.
abstract: OBJECTIVE
  Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival.
  
  
  METHODS
  Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose.
  
  
  RESULTS
  Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.
authors.affiliation: Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, CB# 7305, Chapel Hill, NC 27599-7305, USA. socinski@med.unc.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: David E
authors.initials: DE
authors.lastname: Morris
authors.forename: Jan S
authors.initials: JS
authors.lastname: Halle
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hensing
authors.forename: Steven A
authors.initials: SA
authors.lastname: Limentani
authors.forename: Robert
authors.initials: R
authors.lastname: Fraser
authors.forename: Maureen
authors.initials: M
authors.lastname: Tynan
authors.forename: Andrea
authors.initials: A
authors.lastname: Mears
authors.forename: M Patricia
authors.initials: MP
authors.lastname: Rivera
authors.forename: Frank C
authors.initials: FC
authors.lastname: Detterbeck
authors.forename: Julian G
authors.initials: JG
authors.lastname: Rosenman
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D020266:Radiotherapy, Conformal; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D016190:Carboplatin; D017239:Paclitaxel; D002166:Camptothecin