title: A phase I/II trial of irinotecan plus amrubicin supported with G-CSF for extended small-cell lung cancer.
abstract: OBJECTIVE
  This study reports the findings of a Phase I/II, cohort, dose-escalation trial of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor. This study aimed to determine the dose-limiting toxicity of the combination and to define the maximum-tolerated dose, as a recommended dose for Phase II trials. We also sought to obtain preliminary data on the efficacy of this combination as a frontline therapy for extensive-disease small-cell lung cancer.
  
  
  METHODS
  We included 23 chemo-naïve patients with extensive-disease small-cell lung cancer in the trial. The amrubicin dose was escalated from 35 to 40 mg/m(2) (Levels 1 and 2, respectively) to determine the dose-limiting toxicity, with an unchanged dose of irinotecan at 50 mg/m(2).
  
  
  RESULTS
  Of nine patients, three experienced dose-limiting toxicities at Level 1 of prolonged Grade 4 neutropenia, Grade 3 febrile neutropenia and Grade 3 febrile neutropenia with Grade 3 diarrhea. At Level 2, two patients experienced dose-limiting toxicities of Grade 4 neutropenia and Grade 3 neutropenia with Grade 4 diarrhea. The maximum-tolerated doses and recommended doses for amrubicin and irinotecan were therefore determined to be 35 and 50 mg/m(2), respectively. The Level 1 trial was then expanded to 21 patients, 14 (70%) of whom showed partial responses to the recommended dose. The median progression-free and overall survival times were 6.37 and 15.21 months, respectively.
  
  
  CONCLUSIONS
  The combination of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor produced a potent effect in chemo-naïve extensive-disease small-cell lung cancer patients. The use of biomarkers for this regimen may identify patients who are likely to suffer from treatment-ending severe adverse effects.
authors.affiliation: *3-1-1 Higashi-ku, Maidashi, Fukuoka 812-8582, Japan. harada-t@kokyu.med.kyushu-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Harada
authors.forename: A
authors.initials: A
authors.lastname: Hamada
authors.forename: M
authors.initials: M
authors.lastname: Shimokawa
authors.forename: K
authors.initials: K
authors.lastname: Takayama
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
authors.forename: K
authors.initials: K
authors.lastname: Maeno
authors.forename: S
authors.initials: S
authors.lastname: Saeki
authors.forename: H
authors.initials: H
authors.lastname: Miyawaki
authors.forename: A
authors.initials: A
authors.lastname: Moriyama
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D064147:Febrile Neutropenia / Q000139:chemically induced; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D020011:Protective Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D020011:Protective Agents; D016179:Granulocyte Colony-Stimulating Factor; D000077146:Irinotecan; C055866:amrubicin; D002166:Camptothecin
keywords: chemo-pharmacol; clinical trials; lung-med