Dasatinib: A Review in Chronic Myeloid Leukaemia and Ph+ Acute Lymphoblastic Leukaemia

@article{Keating2016DasatinibAR,
  title={Dasatinib: A Review in Chronic Myeloid Leukaemia and Ph+ Acute Lymphoblastic Leukaemia},
  author={Gillian M. Keating},
  journal={Drugs},
  year={2016},
  volume={77},
  pages={85-96}
}
Dasatinib (Sprycel®) is an orally administered, small molecule inhibitor of multiple tyrosine kinases. In the phase 3 DASISION trial, dasatinib 100 mg once daily resulted in deeper and faster cytogenetic and molecular responses than imatinib 400 mg once daily in patients with newly diagnosed, chronic-phase chronic myeloid leukaemia (CML), although there was no significant between-group difference in progression-free survival (PFS) or overall survival (OS) in the longer term. In the phase 3… 
Dasatinib: A Review in Pediatric Chronic Myeloid Leukemia
TLDR
Dasatinib therapy in pediatric patients with Ph+ CML-CP was reported to have a similar safety profile to that observed in adults, except there were no occurrences of pleural effusions, pericardial effusion, pulmonary edema, or pulmonary hypertension adverse events.
Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia
TLDR
Decitabine plus dasatinib is a safe and active regimen in advanced CML and further studies using this combination are warranted.
A narrative review on adverse effects of dasatinib with a focus on pharmacotherapy of dasatinib-induced pulmonary toxicities
TLDR
Despite the superiority of dasatinib in its hematologic and cytogenetic responses in CML compared to imatinib, its potentially harmful pulmonary complications including pleural effusion (PE) and pulmonary arterial hypertension (PAH) may limit its use.
Clinical Pharmacokinetics and Pharmacodynamics of Dasatinib
TLDR
Dasatinib is an oral, once-daily tyrosine kinase inhibitor used in the treatment of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaamia and is subject to drug interactions with CYP3A4 inducers or inhibitors.
Post-treatment de-phosphorylation of p53 correlates with dasatinib responsiveness in malignant melanoma
TLDR
It is found that treatment-induced de-phosphorylation of p53 correlates with dasatinib responsiveness in malignant melanoma, pending more comprehensive validation in future studies.
A window-of-opportunity clinical trial of dasatinib in women with newly diagnosed endometrial cancer
TLDR
This is the first study to show PK and PD effects of dAsatinib in tumor tissue, allowing evaluation of tissue PD markers as a function of tumor dasatinib concentration, and Dasatinib tissue concentrations at 8 h after dosing were associated with modulation of pTyr419Src, total Src protein, and pT Tyr 419Src/Src ratio.
Dasatinib-induced chylothorax: report of a case and review of the literature
TLDR
A 71-year-old man treated with dasatinib for CML was admitted for progressive dyspnea and the diagnosis of d asatinib-induced chylothorax was identified, the seventh case reported.
Assessing Measurable Residual Disease in Chronic Myeloid Leukemia. BCR-ABL1 IS in the Avant-Garde of Molecular Hematology
TLDR
A mathematical correction for the BCR-ABL1 assay is introduced that could help homogenizing the use of the ABL1 as a control gene and the growing body of evidence concerning treatment-free remission is discussed.
Tyrosine kinase inhibition to improve anthracycline-based chemotherapy efficacy in T-cell lymphoma
TLDR
A modulation of tyrosine kinases belonging to the T-cell receptor pathway upon chemotherapy provided the rationale for combining the tyrosin kinase inhibitor dasatinib with CHOEP, and combination treatment results in tumour growth inhibition in in vivo xenograft mouse models.
...
...

References

SHOWING 1-10 OF 61 REFERENCES
A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia.
TLDR
DAS compared with IM appeared to have more short-term cytogenetic and molecular response, more hematologic toxicity, and similar overall survival.
Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy.
TLDR
Dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients.
Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase.
TLDR
Dasatinib induced significant hematologic and cytogenetic responses in patients with imatinib resistance or intolerance, was well tolerated, and may represent a potent new therapeutic option for CML-AP.
Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia.
  • J. Cortes, Dan Jones, H. Kantarjian
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2010
TLDR
Dasatinib is an effective agent for the initial management of CML in early chronic phase, producing high rates of CCyR and MMR.
Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias.
TLDR
Dasatinib induces hematologic and cytogenetic responses in patients with CML or Ph-positive ALL who cannot tolerate or are resistant to imatinib, which is effective in Philadelphia chromosome-positive leukemias but relapse occurs.
Efficacy and safety of dasatinib versus imatinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP): Subset analysis of the DASISION trial with 2-year follow-up
TLDR
Results of a subset analysis of Japanese patients enrolled in the DASISION trial show safety and efficacy profiles generally consistent with patients enrolled worldwide, including higher response rates with dasatinib compared with imatinib and similar high rates of progression-free and overall survival with both therapies.
Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION).
TLDR
Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR).
Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis.
TLDR
Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML.
Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase
TLDR
Results support the use of dasatinib 100 mg QD as first-line CML treatment in both East Asian and non-East Asian patients.
Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION).
TLDR
The achievement of an early molecular response was predictive of improved progression-free survival and overall survival, supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors.
...
...