title: Combination therapy of hydroxycarbamide with anagrelide in patients with essential thrombocythemia in the evaluation of Xagrid(R) efficacy and long-term safety study.
abstract: Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid(®) Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received hydroxycarbamide + anagrelide. Monotherapies received before this combination were hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581 × 10(9)/L and 411 × 10(9)/L before and after starting hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400 × 10(9)/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600 × 10(9)/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory. (Clinicaltrials.gov identifier:NCT00567502).
authors: luigi.gugliotta@unibo.it.
authors: Luigi
authors: L
authors: Gugliotta
authors: Carlos
authors: C
authors: Besses
authors: Martin
authors: M
authors: Griesshammer
authors: Claire
authors: C
authors: Harrison
authors: Jean-Jacques
authors: JJ
authors: Kiladjian
authors: Ruth
authors: R
authors: Coll
authors: Jonathan
authors: J
authors: Smith
authors: Brihad
authors: B
authors: Abhyankar
authors: Gunnar
authors: G
authors: Birgegård
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011799:Quinazolines; D007372:Interferons; C021139:anagrelide; D006918:Hydroxyurea