title: Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer.
abstract: OBJECTIVE
  Amrubicin is a synthetic anthracycline with potent topoisomerase II inhibition. This phase II study was conducted to confirm safety and activity of amrubicin in the treatment of refractory small-cell lung cancer (SCLC).
  
  
  METHODS
  Patients with refractory SCLC (either with progressive disease as best response or progression within 90 days of first-line therapy) received amrubicin (40 mg/m(2)/d for 3 every 21 days). The primary end point was overall response rate (ORR); secondary end points included progression-free survival (PFS), overall survival (OS), and change in left ventricular ejection fraction (LVEF).
  
  
  RESULTS
  Seventy-five patients with a median progression-free interval after first-line therapy of 38 days were enrolled; 69 patients received a median of four amrubicin cycles (range, one to 12 cycles). The ORR was 21.3% (95% CI, 12.7% to 32.3%), with one complete response (1.3%) and 15 partial responses (20%). Median PFS and OS were 3.2 months (95% CI, 2.4 to 4.0 months) and 6.0 months (95% CI, 4.8 to 7.1 months), respectively. The ORR in 43 patients who never responded to first-line therapy was 16.3% (95% CI, 6.8% to 30.7%). Most commonly reported grade 3 or 4 adverse events included neutropenia (67%), thrombocytopenia (41%), and anemia (30%), with febrile neutropenia in 12%. There was no decrease in mean LVEF with cumulative amrubicin doses exceeding 750 mg/m(2).
  
  
  CONCLUSIONS
  Single-agent amrubicin showed promising activity with a 21.3% ORR and an acceptable safety profile when used as second-line therapy patients with platinum-refractory SCLC. Amrubicin did not induce early cardiotoxicity, but its long-term effects are unknown.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. ettinda@jhmi.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Ettinger
authors.forename: Robert
authors.initials: R
authors.lastname: Jotte
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Vicram
authors.initials: V
authors.lastname: Gupta
authors.forename: Lawrence
authors.initials: L
authors.lastname: Garbo
authors.forename: Carlos
authors.initials: C
authors.lastname: Alemany
authors.forename: Paul
authors.initials: P
authors.lastname: Conkling
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
authors.forename: Chirag
authors.initials: C
authors.lastname: Shah
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.forename: Richard
authors.initials: R
authors.lastname: McNally
authors.forename: Markus F
authors.initials: MF
authors.lastname: Renschler
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Oliver
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; C055866:amrubicin