Date of Award

2012

Degree Type

Selective Evidence-Based Medicine Review

Degree Name

Master of Science in Health Sciences - Physician Assistant

Department

Physician Assistant Studies

Department Chair

John Cavenagh, PhD, PA-C

Abstract

Objective: The objective of this selective EBM review is to determine whether or not dasatinib improves outcomes and tolerability in patients with chronic myeloid leukemia as compared to imatinib.


Study Design: Review of three English language, non-blinded randomized controlled trials from 2009, 2010, and 2010.


Data Sources: Randomized, controlled, non-blinded clinical trials comparing dasatinib to imatinib or comparing dasatinib once daily vs dasatinib twice daily, found using the PubMed database.


Outcomes measured: Overall survival and progression-free survival were measured at one and two years after initiation of therapy. Safety profiles and incidence of adverse effects were also measured. This is graded on a scale of 1 to 4, from lowest in severity to highest in severity. Additionally, adverse effects were noted as hematologic (neutropenia, anemia, thrombocytopenia) or nonhematologic (fluid retention, diarrhea, vomiting, fever).

Results: When comparing dasatinib to imatinib, both drugs provided similar figures for progression-free survival (96% vs 97% respectively) and overall survival (97% vs 99% respectively). However, patients taking dasatinib progressed to accelerated or blastic phases of CML 1.9% of the time, and those taking imatinib progressed 3.5% of the time. Dasatinib had higher rates of hematologic adverse events, and imatinib had higher rates of nonhematologic adverse events.
When comparing dasatinib 140 mg once daily to dasatinib 70 mg twice daily, the twice daily dose produced higher overall survival at 12 months (84% vs 78%) and at 24 months (72% vs 63%), as well as fewer deaths due to progressive disease (43% vs 52%). Rates of nonhematologic adverse events were similar between the two groups. However, the once daily dose lead to lower incidence of gastrointestinal bleeding (8% vs 13%) and pleural effusion (20% vs 39%).

Conclusions: Dasatinib improves outcomes and tolerability in patients with chronic myeloid leukemia as compared to imatinib. This is advantageous not only considering patient quality of life, but also morbidity and mortality from complications such as pleural effusions, congestive heart failure, and bleeding. Additionally, by improving tolerability, patients are less likely to discontinue treatment before completion of a full course of therapy.

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