title: Phase III, single-arm study investigating the efficacy, safety, and tolerability of anagrelide as a second-line treatment in high-risk Japanese patients with essential thrombocythemia.
abstract: Essential thrombocythemia (ET) is usually managed by anti-platelet therapy. European guidelines recommend that patients with ET at high risk of developing thrombohemorrhagic events should be placed on cytoreductive therapy (CRT). In Japan, hydroxycarbamide (HC) is the most widely used CRT; however, treatment options for patients who become intolerant or refractory to initial treatment are limited. This study sought to determine the efficacy, safety, and tolerability of anagrelide in high-risk Japanese adults with ET who were intolerant or refractory to their first-line CRT. Fifty-three patients were enrolled in the study. Of those, 67.9 % had a platelet response (<60 × 10(4)/µL) and 45.3 % achieved normalization of platelet counts (≤40 × 10(4)/µL) on anagrelide therapy. The median time to platelet count response was 98.5 days and the median time to platelet count normalization was 274.0 days. The median daily dose administered was 1.9 mg/day. The most common adverse events observed during anagrelide treatment were anemia, headache, palpitations, and diarrhea. The majority of these were either mild or moderate in severity. Overall, the safety profile of anagrelide in high-risk Japanese patients with ET was consistent with the European Summary of Product Characteristics.
authors.affiliation: Graduate School of Medicine, Osaka University, Osaka University Hospital, C9, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan, kanakura@bldon.med.osaka-u.ac.jp.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: Paul
authors.initials: P
authors.lastname: Wilde
authors.forename: Jonathan
authors.initials: J
authors.lastname: Smith
authors.forename: Heinrich
authors.initials: H
authors.lastname: Achenbach
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011799:Quinazolines / Q000008:administration & dosage* / Q000819:agonists; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
chemical_list: D005343:Fibrinolytic Agents; D011799:Quinazolines; C021139:anagrelide