108 POSTER Phase I study of ABT869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies.

Goh, Boon-Cher; Thang, Carole; Sukri, Norita; Wong, Chin‐Ho; Soo, Ross A.; Carr, Raymond E.; Lee, S.C.; Chen, C.S.; Humerickhouse, R.

doi:10.1016/s1359-6349(06)70114-8

Cited by 3 publications

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“…The target AUC (4.9 μg/h/mL) based on preclinical models was achieved with daily dosing of linifanib at 10 mg. A carboxylate derivative was identified as a major metabolite, suggesting that cytochrome P450 enzymes play a role in the metabolism of linifanib. [12,13]…”

Section: Scientific Summarymentioning

confidence: 99%

Linifanib

2010

Drugs R D

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Section: Scientific Summarymentioning

confidence: 99%

Linifanib

2010

Drugs R D

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“…Hypertension and proteinuria were reversible on dose interruption. [12,13] In a phase I trial in patients who continued treatment with linifanib for >1 year, the common adverse events were myalgia and fatigue. Grade 3 adverse events related to linifanib were fatigue, abdominal pain, and palmar-plantar erythrodysesthesia.…”

Section: Solid Tumorsmentioning

confidence: 99%

“…Clinical data presented at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR-2006) added to the adverse events, pharmacokinetics and Cancer therapeutic trials sections [13] 18 January 2006 Preclinical data presented at the 47th Annual Meeting and Exposition of the American Society of Hematology (ASH-2005) have been added to the Cancer pharmacodynamics section [16] 4 values in the range 3-10 mg/kg/day. Additionally, linifanib showed a >50% inhibition of tumor growth in orthotopic breast, prostate, and glioma models.…”

Section: December 2006mentioning

confidence: 99%

Linifanib

2010

Drugs R D

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Linifanib (A 741439; A-741439; A741439; ABT-869; ABT869; RG3635) is an orally active multi-targeted receptor tyrosine kinase inhibitor for the treatment of various cancers. It was being developed by Roche but development has now reverted to Abbott. The compound is designed to inhibit vascular endothelial growth factor and platelet-derived growth factor receptors. It is in phase III development for liver cancer and phase II development for non-small cell lung cancer, breast cancer, and colorectal cancer in the US, the EU and other areas of the world. This review discusses the key development milestones and therapeutic trials of this drug.

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ETA Receptor Blockade With Atrasentan Prevents Hypertension With the Multitargeted Tyrosine Kinase Inhibitor ABT-869 in Telemetry-instrumented Rats

Banfor¹,

Franklin²,

Segreti³

et al. 2009

Journal of Cardiovascular Pharmacology

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ABT-869 is a novel multitargeted inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases (RTKs) with potent antiangiogenic properties that slow tumor progression. Vascular endothelial growth factor receptor blockade has been shown to produce hypertension. Atrasentan is a potent and selective endothelin (ETA) receptor antagonist that lowers blood pressure and affects tumor growth. To assess the utility of ETA receptor blockade in controlling hypertension with RTK inhibition, we evaluated the ability of atrasentan to block hypertension with ABT-869 in conscious, telemetry-instrumented rats. Changes in mean arterial pressure (MAP) and heart rate (HR) were evaluated using mean values and the area under the curve (AUC). Atrasentan (0.5, 1.5, and 5.0 mg kg(-1) d(-1) for 5 days) elicited dose-dependent decreases in MAP-AUC (-16.7 +/- 1.3, -20.94 +/- 3.68, and -30.12 +/- 3.57 mm Hg x day, respectively) compared with vehicle. ABT-869 (1, 3, 10, 30 mg kg(-1) d(-1) for 5 days) increased MAP compared with vehicle (MAP-AUC values of -5.52 +/- 3.75, 12.7 +/- 8.4, 37.5 +/- 4.4, and 63.8 +/- 3.3 mm Hg x day, respectively). Pretreatment with atrasentan (5 mg/kg for 5 days) prevented and abolished the hypertensive effects of ABT-869. Thus, ETA receptor blockade effectively alleviated hypertension with RTK inhibition and may serve a dual therapeutic role by preventing hypertension and slowing tumor progression.

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108 POSTER Phase I study of ABT869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies.

Cited by 3 publications

References 0 publications

Linifanib

Linifanib

Linifanib

ETA Receptor Blockade With Atrasentan Prevents Hypertension With the Multitargeted Tyrosine Kinase Inhibitor ABT-869 in Telemetry-instrumented Rats

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