Vol 55, No 3 (2024)
Review article
Published online: 2024-06-30
Current status of hydroxyurea in treatment of polycythemia vera
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, 3, 3, 1
DOI: 10.5603/ahp.99436
Acta Haematol Pol 2024;55(3):145-150.
Abstract
Hydroxyurea (HU) is a first-line pharmacotherapy drug used in high-risk patients with polycythemia vera (PV). It has a good tolerability profile, a convenient oral formulation, and a low price. With the increasing availability of other therapeutic options for PV patients, there is a need to redefine the place of HU formulations in the treatment of this condition, and to consider the current criteria for resistance and intolerance to this drug, which may help in accurate decision-making about modifying cytoreductive treatment in PV. This article presents the general characteristics of HU, its position in the therapeutic pathway of PV patients, and the modified resistance and intolerance criteria for this drug.
Keywords: polycythemia verahydroxyureahydroxyurea resistance criteriahydroxyurea intolerance criteriacytoreductive treatment
References
- Grinfeld J, Nangalia J, Baxter EJ, et al. Classification and personalized prognosis in myeloproliferative neoplasms. N Engl J Med. 2018; 379(15): 1416–1430.
- Regimbeau M, Mary R, Hermetet F, et al. Genetic background of polycythemia vera. Genes (Basel). 2022; 13(4): 637.
- Frydecka I. Czerwienica prawdziwa. In: Gajewski P. ed. Interna Szczeklika. Medycyna Praktyczna, Kraków 2022: 1860–1863.
- Krzakowski M. Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych. T. 2. PTOK, Warszawa 2021.
- Tefferi A, Barbui T. Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023; 98(9): 1465–1487.
- Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013; 368(1): 22–33.
- Marchetti M, Vannucchi AM, Griesshammer M, et al. Appropriate management of polycythaemia vera with cytoreductive drug therapy: European LeukemiaNet 2021 recommendations. Lancet Haematol. 2022; 9(4): e301–e311.
- Tefferi A, Lasho TL, Guglielmelli P, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv. 2016; 1(1): 21–30.
- Tefferi A, Guglielmelli P, Lasho TL, et al. Mutation-enhanced international prognostic systems for essential thrombocythaemia and polycythaemia vera. Br J Haematol. 2020; 189(2): 291–302.
- McMullin MF, Harrison CN, Ali S, et al. BSH Committee. A guideline for the diagnosis and management of polycythaemia vera. A British Society for Haematology Guideline. Br J Haematol. 2019; 184(2): 176–191.
- Treatment of polycythaemia vera by radiophosphorus or busulphan: a randomized trial. "Leukemia and Hematosarcoma" Cooperative Group, European Organization for Research on Treatment of Cancer (E.O.R.T.C.). Br J Cancer. 1981; 44(1): 75–80.
- Alvarez-Larrán A, Martínez-Avilés L, Hernández-Boluda JC, et al. Busulfan in patients with polycythemia vera or essential thrombocythemia refractory or intolerant to hydroxyurea. Ann Hematol. 2014; 93(12): 2037–2043.
- Dresler WF, Stein R. Uber den hydroxylharnstoff. Justus Liebigs Ann Chem. 1869; 150(3): 242–252.
- Stearns B, Losee KA, Bernstein J. Hydroxyurea: a new type of potential antitumor agent. J Med Chem. 1963; 6(35): 201.
- Timson J, Timson J. Hydroxyurea. Mutat Res. 1975; 32(2): 115–132.
- Spivak JL, Hasselbalch H. Hydroxycarbamide: a user's guide for chronic myeloproliferative disorders. Expert Rev Anticancer Ther. 2011; 11(3): 403–414.
- Rosner F, Rubin H, Parise F. Studies on the absorption, distribution, and excretion of hydroxyurea (NSC-32065). Cancer Chemother Rep. 1971; 55(2): 167–173.
- Mathur A, Edman J, Liang L, et al. Skin cancer in essential thrombocythaemia and polycythaemia vera patients treated with hydroxycarbamide. EJHaem. 2022; 3(4): 1305–1309.
- Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013; 27(9): 1874–1881.
- Finazzi G, Caruso V, Marchioli R, et al. ECLAP Investigators. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood. 2005; 105(7): 2664–2670.
- Björkholm M, Derolf AR, Hultcrantz M, et al. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms. J Clin Oncol. 2011; 29(17): 2410–2415.
- Wang R, Shallis RM, Stempel JM, et al. Second malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea. Blood Adv. 2023; 7(5): 734–743.
- Hansen IO, Sørensen AL, Hasselbalch HC. Second malignancies in hydroxyurea and interferon-treated Philadelphia-negative myeloproliferative neoplasms. Eur J Haematol. 2017; 98(1): 75–84.
- Fruchtman SM, Mack K, Kaplan ME, et al. From efficacy to safety-a polycythemia vera study group report on Hydroxyurea in patients with polycythemia ver. Semin Hematol. 1997; 34(1): 17–23.
- Barbui T, Vannucchi AM, Finazzi G, et al. A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: A propensity-matched study. Am J Hematol. 2017; 92(11): 1131–1136.
- Alvarez-Larrán A, Pereira A, Cervantes F, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood. 2012; 119(6): 1363–1369.
- Demuynck T, Verhoef G, Delforge M, et al. Polycythemia vera and hydroxyurea resistance/intolerance: a monocentric retrospective analysis. Ann Hematol. 2019; 98(6): 1421–1426.
- Parasuraman S, DiBonaventura M, Reith K, et al. Patterns of hydroxyurea use and clinical outcomes among patients with polycythemia vera in real-world clinical practice: a chart review. Exp Hematol Oncol. 2016; 1(5): 3.
- Barosi G, Birgegard G, Finazzi G, et al. A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. Br J Haematol. 2010; 148(6): 961–963.
- Chiaranairungrot K, Kaewpreechawat K, Sajai C, et al. Prevalence and clinical outcomes of polycythemia vera and essential thrombocythemia with hydroxyurea resistance or intolerance. Hematology. 2022; 27(1): 813–819.
- Alvarez-Larrán A, Kerguelen A, Hernández-Boluda JC, et al. Grupo Español de Enfermedades Mieloproliferativas Filadelfia Negativas (GEMFIN). Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. Br J Haematol. 2016; 172(5): 786–793.
- Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood. 2013; 121(23): 4778–4781.
- Benevolo G, Vassallo F, Urbino I, et al. Polycythemia Vera (PV): Update on Emerging Treatment Options. Ther Clin Risk Manag. 2021; 17: 209–221.
- Beauverd Y, Ianotto JC, Thaw K, et al. Impact of cytoreductive drugs upon outcomes in a contemporary cohort of adolescent and young adults with essential thrombocythemia and polycythemia vera. Blood. 2023; 142(Supplement 1): 748–748.
- Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020; 7(3): e196–e208.
- Abu-Zeinah G, Krichevsky S, Cruz T, et al. Interferon-alpha for treating polycythemia vera yields improved myelofibrosis-free and overall survival. Leukemia. 2021; 35(9): 2592–2601.
- Harrison CN, Nangalia J, Boucher R, et al. Ruxolitinib versus best available therapy for polycythemia vera intolerant or resistant to hydroxycarbamide in a randomized trial. J Clin Oncol. 2023; 41(19): 3534–3544.
- Kiladjian JJ, Zachee P, Hino M, et al. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020; 7(3): e226–e237.
