Adverse effects and benefits of two years of anagrelide treatment for thrombocythemia in chronic myeloproliferative disorders.
OBJECTIVE
Although anagrelide is widely used in the treatment of thrombocythemia in myeloproliferative diseases, there is currently limited information on the efficacy and toxicity of its long-term use. This prospective study investigated clinical toxicity and efficacy of anagrelide during two years of treatment.


METHODS
A multicenter, open, phase II study of anagrelide treatment was performed by the Swedish Myeloproliferative Disorder Study Group. The study included 60 patients with thrombocythemia due to myeloproliferative disease, 42 with essential thrombocythemia (ET), 17 with polycythemia vera (PV) and one with myelofibrosis (MF).


RESULTS
Complete response (CR), defined as a platelet count <400x10(9)/L in symptomatic patients and < 600x10(9)/L in asymptomatic patients was achieved in 67% of the patients and partial response (PR) in 6%. The response rate was higher in patients with ET than in those with PV (p = 0.05). Primary treatment failure occurred in 27% due to lack of efficacy at a tolerable dose (n=13) or insufficient platelet response without side effects (n=3). In addition, another 14 patients withdrew from treatment before the end of the two-year period due to side effects. Side effects included palpitations (70%), headache (52%), nausea (35%), diarrhea or flatulence (33%), edema (22%) and fatigue (23%). Patients and doctors rated their satisfaction with the anagrelide treatment on a 10-grade scale from 7.6 at 3 months to >9 at 24 months. After two years, 50% (n=30) of the patients continued anagrelide treatment.


CONCLUSIONS
Side effects and toxic discontinuation rates were higher than in previous studies, probably because this is the first long-term prospective study of the feasibility and toxicity of anagrelide treatment. Nevertheless, anagrelide is a valuable alternative for treatment of thrombocythemia in myeloproliferative disorders for patients who tolerate the drug well.
Birgegård
Gunnar
G
Dept. Int Medicine, University Hospital, Uppsala, Sweden. Gunnar.Birgegard@medsci.uu.se
Björkholm
Magnus
M
Kutti
Jack
J
Lärfars
Gerd
G
Löfvenberg
Eva
E
Markevärn
Berit
B
Merup
Mats
M
Palmblad
Jan
J
Mauritzson
Nils
N
Westin
Jan
J
Samuelsson
Jan
J
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006261:Headache / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000150:complications*; D009325:Nausea / Q000139:chemically induced; D010349:Patient Compliance; D010352:Patient Dropouts; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D011446:Prospective Studies; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use*; D013922:Thrombocytosis / Q000188:drug therapy* / Q000209:etiology
D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C021139:anagrelide