title: Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer.
abstract: OBJECTIVE
  The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC).
  
  
  METHODS
  Treatment began with two cycles of topotecan (1 mg/m(2)) Days 1 to 5 and paclitaxel (175 mg/m(2)) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard "cohorts of 3" design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m(2)) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade > or =4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade > or =3 dyspnea, or Grade > or =2 pneumonitis.
  
  
  RESULTS
  Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade > or =3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months.
  
  
  CONCLUSIONS
  The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. garces.yolanda@Mayo.edu
authors.forename: Yolanda I
authors.initials: YI
authors.lastname: Garces
authors.forename: Scott H
authors.initials: SH
authors.lastname: Okuno
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
authors.forename: Sumithra J
authors.initials: SJ
authors.lastname: Mandrekar
authors.forename: Brian M
authors.initials: BM
authors.lastname: Bot
authors.forename: John M
authors.initials: JM
authors.lastname: Martens
authors.forename: Donald B
authors.initials: DB
authors.lastname: Wender
authors.forename: Gamini S
authors.initials: GS
authors.lastname: Soori
authors.forename: Dennis F
authors.initials: DF
authors.lastname: Moore
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Kozelsky
authors.forename: James R
authors.initials: JR
authors.lastname: Jett
mesh_terms: D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D016371:Cranial Irradiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011786:Quality Control; D011788:Quality of Life; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D019772:Topotecan / Q000008:administration & dosage
chemical_list: D011838:Radiation-Sensitizing Agents; D005047:Etoposide; D019772:Topotecan; D004999:Amifostine; D017239:Paclitaxel; D002945:Cisplatin