PURPOSE: 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. PATIENTS AND 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). CONCLUSION: 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.
RCT Entities:
PURPOSE: 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. PATIENTS AND 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). CONCLUSION: 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: Brady L Stein; Jason Gotlib; Murat Arcasoy; Marie Huong Nguyen; Neil Shah; Alison Moliterno; Catriona Jamieson; Daniel A Pollyea; Bart Scott; Martha Wadleigh; Ross Levine; Rami Komrokji; Rebecca Klisovic; Krishna Gundabolu; Patricia Kropf; Meir Wetzler; Stephen T Oh; Raul Ribeiro; Rita Paschal; Sanjay Mohan; Nikolai Podoltsev; Josef Prchal; Moshe Talpaz; David Snyder; Srdan Verstovsek; Ruben A Mesa Journal: J Natl Compr Canc Netw Date: 2015-04 Impact factor: 11.908
Authors: Srdan Verstovsek; Alessandro M Vannucchi; Martin Griesshammer; Tamas Masszi; Simon Durrant; Francesco Passamonti; Claire N Harrison; Fabrizio Pane; Pierre Zachee; Keita Kirito; Carlos Besses; Masayuki Hino; Beatriz Moiraghi; Carole B Miller; Mario Cazzola; Vittorio Rosti; Igor Blau; Ruben Mesa; Mark M Jones; Huiling Zhen; Jingjin Li; Nathalie Francillard; Dany Habr; Jean-Jacques Kiladjian Journal: Haematologica Date: 2016-04-21 Impact factor: 9.941
Authors: Brady L Stein; Stephen T Oh; Dmitriy Berenzon; Gabriela S Hobbs; Marina Kremyanskaya; Raajit K Rampal; Camille N Abboud; Kenneth Adler; Mark L Heaney; Elias J Jabbour; Rami S Komrokji; Alison R Moliterno; Ellen K Ritchie; Lawrence Rice; John Mascarenhas; Ronald Hoffman Journal: J Clin Oncol Date: 2015-08-31 Impact factor: 44.544