Combination trastuzumab metronomic low-dose chemotherapy for the treatment of erbB2 overexpressing breast cancer.
Published: 2004
Language: eng
Number of pages: 87
Description: The purpose of these studies was to evaluate the preclinical anti-tumor and antiangiogenic effects of long-term metronomic chemotherapy in combination with trastuzumab relative to standard MTD regimens. Using an orthotopic mammary tumor model with an erbB2 overexpressing variant of MDA-MB-231, SCID mice treated with metronomic or MTD cyclophosphamide (CTX) in combination with trastuzumab showed long-term tumor growth delay compared to single agent therapy. The superior benefit of metronomic dosing was indicated by an absence of severe toxicity. Tumor perfusion and Matrigel assays indicated an additive antiangiogenic effect of metronomic CTX and trastuzumab. Acquired resistance observed after prolonged treatment with trastuzumab alone or combined with CTX was observed and led to studies of possible mechanisms of resistance. Of interest was the upregulation of VEGF and the detection of stable in vivo/in vitro  acquired resistance to trastuzumab. Resistant tumors responded to subsequent treatment with bevacizumab, cetuximab, A12 and in some circumstances, pertuzumab.
Notes: Adviser:  Robert S. Kerbel.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0828.

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