title: Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01.
abstract: OBJECTIVE
  To test the ability of the cytoprotectant, amifostine, to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life (QOL) and swallowing symptoms.
  
  
  METHODS
  A total of 243 patients with stage II to IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m(2) intravenously (IV) days 1 and 22 and carboplatin area under the curve (AUC) days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m(2) IV) and carboplatin (AUC 2), and hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy bid). Patients were randomly assigned at registration to amifostine (AM) 500 mg IV four times per week or no AM during chemoradiotherapy. Beyond standard toxicity end points, physician dysphagia logs (PDLs), daily patient swallowing diaries, and QOL (EORTC QLQ-C30/LC-13) were also collected. Swallowing AUC analyses were calculated from patient diaries and PDLs.
  
  
  RESULTS
  A total of 120 patients were randomly assigned to receive AM, and 122, to receive no AM (one patient was ineligible); 72% received AM per protocol or with a minor deviation. AM was associated with higher rates of acute nausea (P = .03), vomiting (P = .007), cardiovascular toxicity (P = .0001), and infection or febrile neutropenia (P = .03). The rate of >/= grade 3 esophagitis was 30% with AM versus 34% without AM (P = .9). Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine (z test P = .025). QOL was not significantly different between the two arms, except for pain, which showed more clinically meaningful improvement and less deterioration at 6 weeks follow-up (v pretreatment) in the AM arm (P = .003). The median survival rates for both arms were comparable (AM, 17.3 v no AM, 17.9 months; P = .87).
  
  
  CONCLUSIONS
  AM did not significantly reduce esophagitis >/= grade 3 in patients receiving hyperfractionated radiation and chemotherapy. However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies.
authors.affiliation: Department of Radiation Oncology, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202, USA. bmovsas1@hfhs.org
authors.forename: Benjamin
authors.initials: B
authors.lastname: Movsas
authors.forename: Charles
authors.initials: C
authors.lastname: Scott
authors.forename: Corey
authors.initials: C
authors.lastname: Langer
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.forename: Nicos
authors.initials: N
authors.lastname: Nicolaou
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: Mitchell
authors.initials: M
authors.lastname: Machtay
authors.forename: Colum
authors.initials: C
authors.lastname: Smith
authors.forename: Rita
authors.initials: R
authors.lastname: Axelrod
authors.forename: Linda
authors.initials: L
authors.lastname: Sarna
authors.forename: Todd
authors.initials: T
authors.lastname: Wasserman
authors.forename: Roger
authors.initials: R
authors.lastname: Byhardt
mesh_terms: D000368:Aged; D004999:Amifostine / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003680:Deglutition Disorders / Q000209:etiology* / Q000517:prevention & control*; D019583:Dose Fractionation, Radiation; D004941:Esophagitis / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011788:Quality of Life; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D011837:Radiation-Protective Agents; D016190:Carboplatin; D004999:Amifostine; D017239:Paclitaxel