title: Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980.
abstract: OBJECTIVE
  The overall impact of hydroxyurea (HU) or pipobroman treatments on the long-term outcome of patients with polycythemia vera (PV) has not been assessed in randomized studies. We report final analyses from the French Polycythemia Study Group (FPSG) study, which randomly assigned HU versus pipobroman as first-line therapy in 285 patients younger than age 65 years.
  
  
  METHODS
  The full methodology has been described previously. FPSG results were updated with a median follow-up of 16.3 years. Statistical analysis was performed by using competing risks on the intention-to-treat population and according to main treatment received.
  
  
  RESULTS
  Median survival was 17 years for the whole cohort, 20.3 years for the HU arm, and 15.4 years for the pipobroman arm (P = .008) and differed significantly from that in the general population. At 10, 15, and 20 years, cumulative incidence of acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) was 6.6%, 16.5%, and 24% in the HU arm and 13%, 34%, and 52% in the pipobroman arm (P = .004). Cumulative myelofibrosis incidence at 10, 15, and 20 years according to main treatment received was 15%, 24%, and 32% with HU versus 5%, 10%, and 21% with pipobroman (P = .02).
  
  
  CONCLUSIONS
  Data from this unique randomized trial comparing HU with another cytoreductive drug in PV showed that (1) survival of patients with PV treated with conventional agents differed from survival in the general population, (2) evolution to AML/MDS is the first cause of death, (3) pipobroman is leukemogenic and is unsuitable for first-line therapy, and (4) incidence of evolution to AML/MDS with HU is higher than previously reported, although consideration should be given to the natural evolution of PV.
authors.affiliation: Hôpital Saint-Louis, AP-HP, 1 avenue Claude Vellefaux, Paris, France. jean-jacques.kiladjian@sls.aphp.fr
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Christine
authors.initials: C
authors.lastname: Dosquet
authors.forename: Christine
authors.initials: C
authors.lastname: Chomienne
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Rain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010885:Pipobroman / Q000627:therapeutic use*; D011087:Polycythemia Vera / Q000188:drug therapy*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D010885:Pipobroman; D006918:Hydroxyurea