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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3058-3061. Prepublished online as a Blood First Edition Paper on July 5, 2005; DOI 10.1182/blood-2005-04-1422. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1422v1 106/9/3058    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shaked, Y. Articles by Kerbel, R. S. Search for Related Content PubMed PubMed Citation Articles by Shaked, Y. Articles by Kerbel, R. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity Yuval Shaked, Urban Emmenegger, Shan Man, Dave Cervi, Francesco Bertolini, Yaacov Ben-David, and Robert S. Kerbel From the Sunnybrook and Women's College Health Sciences Centre, Molecular and Cellular Biology, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; and the Division of Hematology-Oncology, Department of Medicine, European Institute of Oncology, Milan, Italy. Low-dose metronomic chemotherapy is a promising therapeutic cancer treatment strategy thought to have an antiangiogenic basis. However, the advantages of reduced toxicity, increased efficacy in some cases, and ability to combine chemotherapy administered long term in this way with targeted therapies can be compromised by the empiricism associated with determining the optimum biologic dose (OBD). Using 4 distinct metronomic chemotherapy regimens in 4 different preclinical tumor models, including a hematologic malignancy, we established the OBD by determining the maximum efficacy associated with minimum or no toxicity. We then found each OBD to be strikingly correlated with the maximum reduction in viable peripheral blood circulating vascular endothelial growth factor receptor 2–positive (VEGFR-2+) endothelial precursors (CEPs). These results suggest that CEPs may serve as a pharmacodynamic biomarker to determine the OBD of metronomic chemotherapy regimens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. S. 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The Elusive Optimal Biologic Dose in Phase I Clinical Trials J. Clin. Oncol., September 1, 2006; 24(25): 4054 - 4055. [Full Text] [PDF] R. Buckstein, R. S. Kerbel, Y. Shaked, R. Nayar, C. Foden, R. Turner, C. R. Lee, D. Taylor, L. Zhang, S. Man, et al. High-Dose Celecoxib and Metronomic "Low-dose" Cyclophosphamide Is an Effective and Safe Therapy in Patients with Relapsed and Refractory Aggressive Histology Non-Hodgkin's Lymphoma Clin. Cancer Res., September 1, 2006; 12(17): 5190 - 5198. [Abstract] [Full Text] [PDF] N. Mehra, M. Penning, J. Maas, L. V. Beerepoot, N. van Daal, C. H. van Gils, R. H. Giles, and E. E. Voest Progenitor Marker CD133 mRNA Is Elevated in Peripheral Blood of Cancer Patients with Bone Metastases. Clin. Cancer Res., August 15, 2006; 12(16): 4859 - 4866. [Abstract] [Full Text] [PDF] B. Dome, J. Timar, J. Dobos, L. Meszaros, E. Raso, S. Paku, I. Kenessey, G. Ostoros, M. Magyar, A. Ladanyi, et al. 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Kerbel Antiangiogenic therapy: a universal chemosensitization strategy for cancer? Science, May 26, 2006; 312(5777): 1171 - 1175. [Abstract] [Full Text] [PDF] R. Munoz, S. Man, Y. Shaked, C. R. Lee, J. Wong, G. Francia, and R. S. Kerbel Highly Efficacious Nontoxic Preclinical Treatment for Advanced Metastatic Breast Cancer Using Combination Oral UFT-Cyclophosphamide Metronomic Chemotherapy. Cancer Res., April 1, 2006; 66(7): 3386 - 3391. [Abstract] [Full Text] [PDF] M. Franco, S. Man, L. Chen, U. Emmenegger, Y. Shaked, A. M. Cheung, A. S. Brown, D. J. Hicklin, F. S. Foster, and R. S. Kerbel Targeted Anti-Vascular Endothelial Growth Factor Receptor-2 Therapy Leads to Short-term and Long-term Impairment of Vascular Function and Increase in Tumor Hypoxia. Cancer Res., April 1, 2006; 66(7): 3639 - 3648. [Abstract] [Full Text] [PDF] U. Emmenegger, G. C. Morton, G. Francia, Y. Shaked, M. Franco, A. Weinerman, S. Man, and R. S. Kerbel Low-Dose Metronomic Daily Cyclophosphamide and Weekly Tirapazamine: A Well-Tolerated Combination Regimen with Enhanced Efficacy That Exploits Tumor Hypoxia Cancer Res., February 1, 2006; 66(3): 1664 - 1674. [Abstract] [Full Text] [PDF]

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