title: Randomized phase 2 study of subcutaneous amifostine versus epoetin-alpha given 3 times weekly during concurrent chemotherapy and hyperfractionated radiotherapy for limited-disease small cell lung cancer.
abstract: BACKGROUND
  The purpose of the current study was to investigate the role of amifostine and epoetin-alpha in reducing severe toxicities during concurrent chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC).
  
  
  METHODS
  Seventy-six patients with LD-SCLC were enrolled. The treatment schedule was consisted of two 28-day cycles of cisplatin at a dose of 30 mg/m2 (Days 1 and 8) and irinotecan at a dose of 60 mg/m2 (Days 1, 8, and 15) followed by two 21-day cycles of cisplatin at a dose of 60 mg/m2 (Day 1) and etoposide at a dose of 100 mg/m2 (Days 1-3) with concurrent twice-daily thoracic radiotherapy for a total of 45 grays. Patients were randomly assigned at registration to either amifostine at a dose of 500 mg or epoetin-alpha at a dose of 10,000 IU subcutaneously 3 times weekly (n = 36 patients and 40 patients, respectively). Fifteen of 36 patients assigned to the amifostine arm did not receive amifostine because of a lack of supply.
  
  
  RESULTS
  Amifostine treatment was associated with higher febrile neutropenia (P = .003) and grade 2 or 3 nausea (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) (P = .03). It also demonstrated a trend toward higher grade 4 leukopenia (P = .05). Grade 3 esophagitis was reported in 30% of patients treated with amifostine and 9% of patients treated with epoetin-alpha (P = .059). Epoetin-alpha treatment was associated with less grade 2 or 3 anemia (P = .031) and lower decreases in hemoglobin level during CCRT (P = .016). The median survival times for both treatment arms were comparable (22.6 months in the amifostine arm vs 25.6 months in the epoetin-alpha arm; P = .447).
  
  
  CONCLUSIONS
  Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin-alpha was effective in preventing severe anemia during CCRT in patients with LD-SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated.
authors.affiliation: Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: Hye-Suk
authors.initials: HS
authors.lastname: Han
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yu
authors.forename: Hong Ryull
authors.initials: HR
authors.lastname: Pyo
authors.forename: Hyae Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Kwan Ho
authors.initials: KH
authors.lastname: Cho
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Heung Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000368:Aged; D004999:Amifostine / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011994:Recombinant Proteins; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D004999:Amifostine