Naslov
Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis

Autori
Ostojić, Alen ; Vrhovac, Radovan ; Verstovšek, Srđan

Izvornik
Future Oncology (1479-6694) 7 (2011), 9; 1035-1043

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
JAK2 inhibitor; JAK2V617F mutation; myelofibrosis; ruxolitinib

Sažetak
Ruxolitinib (INCB018424) is the first potent, selective, oral inhibitor of JAKs 1 and 2 being developed for clinical use. Its major cellular and systemic effects are proliferation inhibition, apoptosis induction, and reduction in cytokine plasma levels, all mediated by the drug’s inhibition of JAKs’ ability to phosphorylate STAT. In initial clinical trials of its use in myelofibrosis, ruxolitinib exhibited durable efficacy in reduction of splenomegaly and alleviation of constitutional symptoms. Patients also showed weight gain and improvement in general physical condition. The dose-limiting toxicity was thrombocytopenia. In preliminary findings of a phase III trial in patients with primary, post- polycythemia-vera, or post-essential- thrombocythemia myelofibrosis, administration at an initial dosage of 15 or 20 mg twice daily led to a spleen-volume response rate (≥35% reduction at 24 weeks) of 41.9%, vs. 0.7% for placebo (p < 0.0001) ; further, 45.9% of the ruxolitinib recipients had ≥50% improvement in symptom score (on the modified Myelofibrosis Symptom Assessment Form version 2.0), vs. 5.3% for placebo (p < 0.0001). Ruxolitinib recipients also showed improvement in parameters of quality of life.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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