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Phase II Study of the Oral MEK Inhibitor AZD6244 in Advanced Acute Myeloid Leukemia (AML).

Publication ,  Conference
Odenike, O; Curran, E; Iyengar, N; Popplewell, L; Kirschbaum, M; Erba, HP; Green, M; Poiré, X; Ihonor, P; Diaz-Flores, E; Shannon, K; Wade, JL ...
Published in: Blood
November 20, 2009

Abstract 2081Poster Board II-58AZD6244 is an orally bioavailable small molecule inhibitor of the MEK kinase. MEK is downstream of the RAS/RAF pathway, which is activated by mutations occurring in RAS as well as mutations and/or overexpression of upstream receptor tyrosine kinases such as FLT3 and c-KIT in AML. In addition, elevated levels of phosphorylated-ERK (p-ERK), the only known substrate of MEK, have been demonstrated in >75% of patients(pts) with AML, and MEK inhibition of primary AML cells in vitro results in growth arrest. AZD6244 was well tolerated in phase I trials in advanced solid tumors and had a favorable pharmacokinetic profile; the recommended phase II dose was 100mg twice daily. We hypothesized that in AML, a MEK inhibitor would lead to inhibition of RAS-mediated signal transduction, with subsequent antiproliferative effects and inhibition of the leukemia clone. We report our experience with the first clinical trial utilizing a MEK inhibitor in advanced AML.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 20, 2009

Volume

114

Issue

22

Start / End Page

2081 / 2081

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Odenike, O., Curran, E., Iyengar, N., Popplewell, L., Kirschbaum, M., Erba, H. P., … Stock, W. (2009). Phase II Study of the Oral MEK Inhibitor AZD6244 in Advanced Acute Myeloid Leukemia (AML). In Blood (Vol. 114, pp. 2081–2081). American Society of Hematology. https://doi.org/10.1182/blood.v114.22.2081.2081
Odenike, Olatoyosi, Emily Curran, Neil Iyengar, Leslie Popplewell, Mark Kirschbaum, Harry P. Erba, Margaret Green, et al. “Phase II Study of the Oral MEK Inhibitor AZD6244 in Advanced Acute Myeloid Leukemia (AML).” In Blood, 114:2081–2081. American Society of Hematology, 2009. https://doi.org/10.1182/blood.v114.22.2081.2081.
Odenike O, Curran E, Iyengar N, Popplewell L, Kirschbaum M, Erba HP, et al. Phase II Study of the Oral MEK Inhibitor AZD6244 in Advanced Acute Myeloid Leukemia (AML). In: Blood. American Society of Hematology; 2009. p. 2081–2081.
Odenike, Olatoyosi, et al. “Phase II Study of the Oral MEK Inhibitor AZD6244 in Advanced Acute Myeloid Leukemia (AML).Blood, vol. 114, no. 22, American Society of Hematology, 2009, pp. 2081–2081. Crossref, doi:10.1182/blood.v114.22.2081.2081.
Odenike O, Curran E, Iyengar N, Popplewell L, Kirschbaum M, Erba HP, Green M, Poiré X, Ihonor P, Diaz-Flores E, Shannon K, Atallah E, Wade JL, Perdekamp M, Nattam S, Thomas SP, Smith SE, Doyle LA, Rich ES, Larson RA, Stock W. Phase II Study of the Oral MEK Inhibitor AZD6244 in Advanced Acute Myeloid Leukemia (AML). Blood. American Society of Hematology; 2009. p. 2081–2081.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 20, 2009

Volume

114

Issue

22

Start / End Page

2081 / 2081

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology