title: A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours.
abstract: BACKGROUND
  Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients. This phase III randomised trial compares conventional salvage to high-dose-intensification chemotherapy.
  
  
  METHODS
  Between February 1994 and September 2001, 280 patients from 43 institutions in 11 countries, were randomly assigned to receive either four cycles of cisplatin, ifosfamide and etoposide (or vinblastine) (arm A), or three such cycles followed by high-dose carboplatin, etoposide and cyclophosphamide (CarboPEC) with haematopoietic stem cell support (arm B).
  
  
  RESULTS
  Similar complete and partial response rates were observed in both treatment arms (56%; 95% CI 50% to 62%). There were 3% and 7% toxic deaths in arms A and B, respectively. No significant improvements with CarboPEC were observed in either 3-year event-free survival (35% versus 42%, P=0.16) or overall survival (53%; 95% CI 46% to 59%). Complete responders with CarboPEC had a significant improvement in disease-free survival (55% versus 75% at 3 years, P <0.04).
  
  
  CONCLUSIONS
  The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes. These results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Pico
authors.forename: G
authors.initials: G
authors.lastname: Rosti
authors.forename: A
authors.initials: A
authors.lastname: Kramar
authors.forename: H
authors.initials: H
authors.lastname: Wandt
authors.forename: V
authors.initials: V
authors.lastname: Koza
authors.forename: R
authors.initials: R
authors.lastname: Salvioni
authors.forename: C
authors.initials: C
authors.lastname: Theodore
authors.forename: G
authors.initials: G
authors.lastname: Lelli
authors.forename: W
authors.initials: W
authors.lastname: Siegert
authors.forename: A
authors.initials: A
authors.lastname: Horwich
authors.forename: M
authors.initials: M
authors.lastname: Marangolo
authors.forename: W
authors.initials: W
authors.lastname: Linkesch
authors.forename: G
authors.initials: G
authors.lastname: Pizzocaro
authors.forename: H-J
authors.initials: HJ
authors.lastname: Schmoll
authors.forename: J
authors.initials: J
authors.lastname: Bouzy
authors.forename: J-P
authors.initials: JP
authors.lastname: Droz
authors.forename: P
authors.initials: P
authors.lastname: Biron
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D016879:Salvage Therapy; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014747:Vinblastine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide