American Society of Clinical Oncology: Dasatinib (Sprycel)

Posted by James

The tyrosine kinase inhibitor (TKI) dasatinib (Sprycel, Bristol-Myers Squibb) is approved for the second-line treatment of chronic myeloid leukemia (CML) that is resistant to imatinib mesylate (Gleevec, Novartis). Most TKIs have long half-lives, resulting in continuous target inhibition, according to Dr. Shah. Because dasatinib has a short half-life (3 to 5 hours, compared with 18 to 60 hours with other TKIs), twice-daily dosing (70 mg) was chosen to provide more consistent target inhibition in phase 2 studies of dasatinib. The adverse event of pleu-ral effusions, however, was more common with twice-daily dosing in early studies, whereas the major cytogenetic response rate with once-daily dosing was equivalent to that for patients who were treated twice a day.

To determine whether transient (once-daily) target inhibition allowed for equivalent efficacy and improved toxicity, compared with more continuous inhibition, Dr. Shah and his colleagues evaluated 662 patients with chronic-phase CML. Enrolled participants were randomly assigned to receive dasatinib at 100 mg or 140 mg once daily or twice daily.

The median duration of treatment was 11.5 months. Complete hematological response, major cytogenetic response, and complete cytogenetic response rates were similar for all treatment groups (Table 1). Progression-free survival was significantly longer with a dose of 100 mg once daily, compared with 70 mg twice daily (16 patients with disease progression vs. 30 patients with disease progression, respectively; P = 0.032). canadian antibiotics

Table 1 Dasatinib and Chronic Myeloid Leukemia: Hematological and Cytogenetic Responses

	100 mg	50 mg	140 mg	70 mg
	Once	Twice	Once	Twice
Dose/Response	Daily (%)	Daily (%)	Daily (%)	Daily (%)
Complete hematological response	92	93	88	89
Major cytogenetic response	64	58	62	58
Complete cytogenetic response	46	46	47	50

Grade 3 and 4 nonhematological side effects were generally similar for all groups. For hematological grade 3 and 4 events, thrombocytopenia was significantly less common with dasa.