title: Phase I study of concurrent chemoradiation with pemetrexed and cisplatin followed by consolidation pemetrexed for patients with unresectable stage III non-small cell lung cancer.
abstract: OBJECTIVE
  Although concurrent chemotherapy and radiation is the standard approach for good risk unresectable stage III non-small cell lung cancer (NSCLC) patients, there is no optimal concurrent chemotherapy regimen. Administration of chemotherapy at full dose with maximal activity against local and micrometastatic disease is highly desirable. This study tested the feasibility of 3 cycles of full dose cisplatin and pemetrexed concurrent with definitive thoracic radiotherapy followed by consolidation pemetrexed, without the dose-limiting toxicity (DLT) exceeding 33% of the patients.
  
  
  METHODS
  Patients with unresectable stage III NSCLC, good performance status and no serious comorbidity were eligible. Patients received thoracic radiation to a dose of 66 Gy concurrently with three 21-day cycles of pemetrexed 500 mg/m(2), and cisplatin at escalating doses from 60 to 75 mg/m(2). Consolidation chemotherapy of pemetrexed 500 mg/m(2) was provided for 3 more 21-day cycles. Cisplatin doses were escalated as far as no more than 1/3 of the patients in a level developing dose limiting toxicities (DLT).
  
  
  RESULTS
  Fifteen eligible patients were enrolled: nine in the first dose level and 3 in the second and third dose levels respectively. Two out of 9 patients in the first dose level experienced DLT (grade 3 esophagitis resulting in delay in treatment administration). The major serious acute toxicities were esophagitis (40%) and febrile neutropenia (20%). With a median follow up time of 22 months, median time to progression and overall survival has not been reached. The rate of survival at 24 months was 57.5% (95% CI: 27.5-87.4%) of the patients.
  
  
  CONCLUSIONS
  Three systemic dose levels of pemetrexed and cisplatin could be administered concurrently with radiotherapy. The rate of survival at 24 months was encouraging.
authors.affiliation: Institut Català d'Oncologia, L'Hospitalet, Barcelona, Spain. fcardenal@iconcologia.net
authors.forename: Felipe
authors.initials: F
authors.lastname: Cardenal
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Arnaiz
authors.forename: Teresa
authors.initials: T
authors.lastname: Morán
authors.forename: Josep
authors.initials: J
authors.lastname: Jové
authors.forename: Ernest
authors.initials: E
authors.lastname: Nadal
authors.forename: Ruth
authors.initials: R
authors.lastname: Porta
authors.forename: Josep María
authors.initials: JM
authors.lastname: Solé
authors.forename: Isabel
authors.initials: I
authors.lastname: Brao
authors.forename: Ramón
authors.initials: R
authors.lastname: Palmero
authors.forename: Rafael
authors.initials: R
authors.lastname: Fuentes
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Núñez
authors.forename: Elena
authors.initials: E
authors.lastname: Caveda
authors.forename: Alejo
authors.initials: A
authors.lastname: Cassinello
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D060830:Consolidation Chemotherapy; D018450:Disease Progression; D004941:Esophagitis / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed; D016019:Survival Analysis
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin