Phase I and Biomarker Study of ABT-869, a Multiple Receptor Tyrosine Kinase Inhibitor, in Patients With Refractory Solid Malignancies

Wong, Chin‐Ho; Koh, Thiam-Seng; Soo, Ross A.; Hartono, Septian; Thng, Choon-Hua; McKeegan, Evelyn; Yong, Wei‐Peng; Chen, Chien-Shing; Lee, Soo‐Chin; Wong, John; Lim, Robert; Sukri, Norita; Lim, Siak Piang; Ong, Ashley Li Kuan; Steinberg, Joyce; Gupta, Neeraj; Pradhan, Rajendra; Humerickhouse, Rod; Goh, Boon-Cher

doi:10.1200/jco.2008.21.7125

Cited by 81 publications

(70 citation statements)

References 27 publications

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“…Studies done previously have shown linifanib as an inhibitor of PI3K/AKT, mitogen-activated protein kinase pathways in acute myeloid leukemia [36,37] and also the expression of VEGF in several types of cancers. [38,39] The combination of linifanib with radiation has shown better results than either of them being employed alone according to the preliminary data available.…”

Section: Motesanibmentioning

confidence: 96%

Vascular normalization window: A positive prognostic foresight for head and neck cancer

Asha¹,

Dua²,

Rajarathnam³

et al. 2015

JCRI

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Tumor angiogenesis is a hallmark of advanced cancers which is critical for the continued growth and progression of solid tumors owing to the metastatic spread of tumor cells. This knowledge has led to the concept of targeting the tumor vasculature as a therapeutic modality. Several retrospective studies support the positive prognosis for the implications of angiogenic markers for head and neck squamous cell carcinoma (HNSCC), currently making them an attractive target oriented treatment. Radiotherapy (RT) being the conventional treatment for HNSCC, makes it imperative in this present era to recognize the communication between antiangiogenic therapy and RT, thus developing a combination therapy to achieve progress in the outcome of clinical practice. The combination of antiangiogenic agents and ionizing radiation involve many interactions between the cells, the stroma of the tumor and tissue vasculature. Increased angiogenesis is responsible for the proliferation of tumor cells and its metastasis which ultimately leads to tumor hypoxia. Any agent targeting the tumor vasculature can modulate the tumor microenvironment thus normalizing it and enhancing the therapeutic response of hypoxic cells of head and neck cancers. This review provides insight into the mechanisms by which the antiangiogenic therapy combined with RT improves the tumor response to radiation, thereby suggesting a promising prognostic treatment modality of HNSCC in the time ahead.

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Section: Motesanibmentioning

confidence: 96%

Vascular normalization window: A positive prognostic foresight for head and neck cancer

Asha¹,

Dua²,

Rajarathnam³

et al. 2015

JCRI

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“…Linifanib showed single agent in several tumours including non-small lung cancer, CRC, ovarian cancer, hepatocellular carcinoma, neuroendocrine tumor, renal cell carcinoma and alveolar soft part sarcoma [49]. Very recently, linifanib added to standard platinum-based chemotherapy showed to be safe and active in non-squamous NSCLC patients [50].…”

Section: Linifanibmentioning

confidence: 99%

Novel anti-angiogenic therapeutic strategies in colorectal cancer

Tampellini

Sonetto

Scagliotti

2016

Expert Opinion on Investigational Drugs

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“…Two patients in study M06-879 had received drug treatment every other day rather than every day. [9] Phase I : Analysis of preliminary results from a phase I trial of linifanib showed that 15 patients exhibited adverse events of grade 2 or higher; hypertension (12); neutropenia (4), thrombocytopenia (3), and hand foot syndrome (2). Two patients experienced a dose limiting toxicity; one each of grade 3 ALT increase at 0.10 mg/kg and ECG T-wave inversion at 0.25 mg/kg.…”

Section: Solid Tumorsmentioning

confidence: 99%

“…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%

“…16 September 2008 Efficacy, adverse events and pharmacokinetics data from phase I and phase II trials in solid tumors presented at the 33rd Congress of the European Society for Medical Oncology (ESMO-2008) [8,9] 31 [12] 28 June 2007 Abbott Laboratories and Genetech Inc. have entered into a collaboration for the research, development and commercialization of two of Abbott's anti-cancer candidates, including ABT 869…”

Section: Cancermentioning

confidence: 99%

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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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Phase I and Biomarker Study of ABT-869, a Multiple Receptor Tyrosine Kinase Inhibitor, in Patients With Refractory Solid Malignancies

Abstract: ABT-869 by continuous once-daily dosing was tolerable at doses

Cited by 81 publications

References 27 publications

Vascular normalization window: A positive prognostic foresight for head and neck cancer

Vascular normalization window: A positive prognostic foresight for head and neck cancer

Novel anti-angiogenic therapeutic strategies in colorectal cancer

Linifanib

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