title: Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer.
abstract: OBJECTIVE
  The irinotecan-cisplatin combination has emerged as a new standard for the treatment of advanced-stage small-cell lung cancer (AS-SCLC). To move forward we developed a 3-day regimen of cisplatin, etoposide and irinotecan.
  
  
  METHODS
  Successive cohorts of AS-SCLC patients were treated with irinotecan administered as a single 1-h infusion in combination with fixed doses of cisplatin (20 mg/m(2)) and etoposide (75 mg/m(2)), both given for three consecutive days (ECI regimen). Irinotecan dose was escalated from 60 mg/m(2) by 40-mg/m(2) increments. At mid-step between the maximum tolerated dose (MTD) and the previous dose level, patients were randomized for the day of administration of irinotecan (day 1 vs day 3).
  
  
  RESULTS
  A total of 36 AS-SCLC patients received 166 courses of treatment at four dose levels. The MTD of irinotecan was 140 mg/m(2) (three dose-limiting toxicities, DLTs), and the recommended optimal dose (ROD) 120 mg/m(2) (two DLTs). DLTs were febrile neutropenia and grade 3 diarrhea. Other toxicities were mild. No difference in toxicity was seen between the two time schedules. A 77% (95% CI 63.25-90.75%) response rate was recorded among 31 evaluable patients and the median survival was 12 months.
  
  
  CONCLUSIONS
  The ECI regimen was well tolerated and showed considerable activity in patients with AS-SCLC. Phase II/III evaluation is ongoing.
authors.affiliation: Medical Oncology Department, University Hospital, Ioannina, Greece. ebriasou@otenet.gr
authors.forename: E
authors.initials: E
authors.lastname: Briasoulis
authors.forename: E
authors.initials: E
authors.lastname: Samantas
authors.forename: H
authors.initials: H
authors.lastname: Kalofonos
authors.forename: D
authors.initials: D
authors.lastname: Skarlos
authors.forename: T
authors.initials: T
authors.lastname: Makatsoris
authors.forename: C
authors.initials: C
authors.lastname: Christodoulou
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
authors.forename: A
authors.initials: A
authors.lastname: Bamias
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: P
authors.initials: P
authors.lastname: Kosmidis
authors.forename: N
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin