Journal article
Phase I trial of a monoclonal antibody specific for αvβ3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion
Clinical cancer research, Vol.11(21), pp.7851-7860
11/01/2005
DOI: 10.1158/1078-0432.CCR-05-0262
PMID: 16278408
Abstract
At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the αvβ3 integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the αvβ3 integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at αvβ3 could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the αvβ3 integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on treatment. With this weekly schedule of administration, and in the doses studied, MEDI-522 seems to be without significant toxicity, may have effects on tumor perfusion, and may have clinical activity in renal cell cancer. These findings suggest the MEDI-522 could be further investigated as an antiangiogenic agent for the treatment of cancer.
Details
- Title: Subtitle
- Phase I trial of a monoclonal antibody specific for αvβ3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion
- Creators
- Douglas G Mcneel - University of Wisconsin Carbone Cancer CenterJens Eickhoff - University of Wisconsin Carbone Cancer CenterJIANLIANG Zhang - MedImmune Oncology, Inc, Gaithersburg, Maryland, United StatesLuz Hammershaimb - MedImmune Oncology, Inc, Gaithersburg, Maryland, United StatesJames A Zwiebel - National Cancer InstituteGeorge Wilding - University of Wisconsin Carbone Cancer CenterFred T Lee - University of Wisconsin–MadisonDavid M King - University of Wisconsin Carbone Cancer CenterDona Alberti - University of Wisconsin Carbone Cancer CenterJames P Thomas - University of Wisconsin Carbone Cancer CenterAndreas Friedl - University of Wisconsin Carbone Cancer CenterJill Kolesar - University of Wisconsin Carbone Cancer CenterRebecca Marnocha - University of Wisconsin Carbone Cancer CenterJennifer Volkman - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.11(21), pp.7851-7860
- Publisher
- American Association for Cancer Research
- DOI
- 10.1158/1078-0432.CCR-05-0262
- PMID
- 16278408
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- NCI NIH HHS: N02-CO-124001, U01 CA62491, U01 CA062491 NCRR NIH HHS: M01 RR03186
- Language
- English
- Date published
- 11/01/2005
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696551302771
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