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A phase II study of vorinostat ( MK ‐0683) in patients with polycythaemia vera and essential thrombocythaemia
Author(s) -
Andersen Christen L.,
McMullin Mary F.,
Ejerblad Elisabeth,
Zweegman Sonja,
Harrison Claire,
Fernandes Savio,
Bareford David,
Knapper Steven,
Samuelsson Jan,
Löfvenberg Eva,
Linder Olle,
Andreasson Bjørn,
Ahlstrand Erik,
Jensen Morten K.,
Bjerrum Ole W.,
Vestergaard Hanne,
Larsen Herdis,
Klausen Tobias W.,
MouritsAndersen Torben,
Hasselbalch Hans C.
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12416
Subject(s) - medicine , polycythaemia , discontinuation , vorinostat , polycythemia vera , adverse effect , gastroenterology , essential thrombocythemia , histone deacetylase , biochemistry , chemistry , gene , histone
Summary Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator‐initiated, non‐randomized, open‐label phase II multi‐centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by E uropean L eukaemia N et. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention‐to‐treat response rate of 35% was identified. Pruritus was resolved [19% to 0% ( P = 0·06)] and the prevalence of splenomegaly was lowered from 50% to 27% ( P = 0·03). Sixty‐five per cent of the patients experienced a decrease in JAK 2 V617F allele burden ( P = 0·006). Thirty‐three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.