title: Randomised phase II study of amrubicin as single agent or in combination with cisplatin versus cisplatin etoposide as first-line treatment in patients with extensive stage small cell lung cancer - EORTC 08062.
abstract: OBJECTIVE
  The EORTC 08062 phase II randomised trial investigated the activity and safety of single agent amrubicin, cisplatin combined with amrubicin, and cisplatin combined with etoposide as first line treatment in extensive disease (ED) small cell lung cancer (SCLC).
  
  
  METHODS
  Eligible patients with previously untreated ED-SCLC, WHO performance status (PS) 0-2 and measurable disease were randomised to 3 weekly cycles of either amrubicin alone 45mg/m(2) i.v. day(d) 1-3 (A), cisplatin 60mg/m(2) i.v. d1 and amrubicin 40mg/m(2) i.v. d1-3 (PA), or cisplatin 75mg/m(2) i.v. d1 and etoposide 100mg/m(2) d1, d2-3 i.v./po (PE). The primary end-point was overall response rate (ORR) as assessed by local investigators (RECIST1.0 criteria). Secondary end-points were treatment toxicity, progression-free survival and overall survival.
  
  
  RESULTS
  The number of randomised/eligible patients who started treatment was 33/28 in A, 33/30 in PA and 33/30 in PE, respectively. Grade (G) ⩾3 haematological toxicity in A, PA and PE was neutropenia (73%, 73%, 69%); thrombocytopenia (17%, 15%, 9.4%), anaemia (10%, 15%, 3.1%) and febrile neutropenia (13%, 18%, 6%). Early deaths, including treatment related, occurred in 1, 3 and 3 patients in A, PA and PE arms, respectively. Cardiac toxicity did not differ among the 3 arms. Out of 88 eligible patients who started treatment, ORR was 61%, (90% 1-sided confidence intervals [CI] 47-100%), 77% (CI 64-100%) and 63%, (CI 50-100%) for A, PA and PE respectively.
  
  
  CONCLUSIONS
  All regimens were active and PA met the criteria for further investigation, despite slightly higher haematological toxicity.
authors.affiliation: The Royal Marsden Hospital, Sutton, United Kingdom. mary.obrien@rmh.nhs.uk
authors.forename: Mary E R
authors.initials: ME
authors.lastname: O'Brien
authors.forename: Krzystof
authors.initials: K
authors.lastname: Konopa
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Lionel
authors.initials: L
authors.lastname: Bosquee
authors.forename: Ernest
authors.initials: E
authors.lastname: Marshall
authors.forename: Frederique
authors.initials: F
authors.lastname: Bustin
authors.forename: Sabine
authors.initials: S
authors.lastname: Margerit
authors.forename: Christian
authors.initials: C
authors.lastname: Fink
authors.forename: Jos A
authors.initials: JA
authors.lastname: Stigt
authors.forename: Anne Marie C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: Baktiar
authors.initials: B
authors.lastname: Hasan
authors.forename: Jan
authors.initials: J
authors.lastname: Van Meerbeeck
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005060:Europe; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D005047:Etoposide; C055866:amrubicin; D002945:Cisplatin