title: Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP).
abstract: BACKGROUND
  This Australian single-arm, multicenter, phase II trial evaluated feasibility, tolerability and activity of accelerated bleomycin, etoposide and cisplatin (BEP) as first-line chemotherapy for metastatic germ cell tumours.
  
  
  METHODS
  Patients were planned to receive cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) days 1-5, and pegfilgrastim 6 mg day 6, all repeated every 2 weeks for four cycles (three cycles for good prognosis). Bleomycin was given at 30 000 IU weekly to a total of 12 doses (9 doses for good prognosis). Primary end point was feasibility, defined as the proportion of patients able to complete the etoposide and cisplatin components of BEP and be eligible to receive a fourth cycle of BEP by day 50.
  
  
  RESULTS
  Twelve poor, 16 intermediate and 15 good prognosis (n = 43) eligible patients were enrolled. Two patients aged >40 years were ineligible and excluded from analyses. The regimen was feasible in 86%, not feasible in 7% and not assessable in 7% of patients. Most common grade 3/4 adverse events were non-neutropenic infection (16%) and febrile neutropenia (12%). Complete response (CR) to chemotherapy and surgery was achieved in 33% poor-prognosis, 81% intermediate-prognosis and 100% good-prognosis patients. At median follow-up of 27 months (range 6-42), the 2-year progression-free survival was 50% for poor-prognosis, 94% for intermediate-prognosis and 92% for good-prognosis patients.
  
  
  CONCLUSIONS
  Accelerated BEP is feasible and tolerable. Efficacy data appear to be promising. This trial and a similar UK study provide the rationale for a randomised trial comparing accelerated versus standard BEP. Australian New Zealand Clinical Trials Registry Registration number. ACTRN 12607000294459.
authors.affiliation: NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors.forename: P S
authors.initials: PS
authors.lastname: Grimison
authors.forename: M R
authors.initials: MR
authors.lastname: Stockler
authors.forename: M
authors.initials: M
authors.lastname: Chatfield
authors.forename: D B
authors.initials: DB
authors.lastname: Thomson
authors.forename: V
authors.initials: V
authors.lastname: Gebski
authors.forename: M
authors.initials: M
authors.lastname: Friedlander
authors.forename: A L
authors.initials: AL
authors.lastname: Boland
authors.forename: B
authors.initials: B
authors.lastname: Houghton
authors.forename: H
authors.initials: H
authors.lastname: Gurney
authors.forename: M
authors.initials: M
authors.lastname: Rosenthal
authors.forename: N
authors.initials: N
authors.lastname: Singhal
authors.forename: G
authors.initials: G
authors.lastname: Kichenadasse
authors.forename: S S
authors.initials: SS
authors.lastname: Wong
authors.forename: C R
authors.initials: CR
authors.lastname: Lewis
authors.forename: P A
authors.initials: PA
authors.lastname: Vasey
authors.forename: G C
authors.initials: GC
authors.lastname: Toner
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000556:secondary; D011379:Prognosis; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin
keywords: accelerated; antineoplastic combined chemotherapy; dose-density; germ cell tumours; growth factors; testicular neoplasms