Abstract
Recombinant humanized anti-HER2 antibody, rhuMAb HER2, inhibits the growth of breast cancer cells overexpressing HER2 and has clinical activity. We explored in preclinical models its capacity to enhance the tumoricidal effects of paclitaxel and doxorubicin. In cultures of naturally HER2-overexpressing cancer cells, rhuMAb HER2 inhibited growth and enhanced the cytotoxic effects of paclitaxel. Treatment of well established BT-474 breast cancer xenografts overexpressing HER2 in athymic mice with rhuMAb HER2 resulted in a dose-dependent antitumor activity. In combination studies, treatment with paclitaxel and rhuMAb HER2 or doxorubicin and rhuMAb HER2 resulted in greater inhibition of growth than that observed with any agent alone. The combination of paclitaxel and rhuMAb HER2 resulted in the highest tumor growth inhibition and had a significantly superior complete tumor regression rate when compared with either paclitaxel or rhuMAb HER2 alone. Clinical trials that are built on these results are under way.
Footnotes
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↵1 Supported in part by an American Society of Clinical Oncology Career Development Award (to J. B.), NIH Grant CA65746, and Specialized Programs of Research Excellence Grant p50-CA58207 from The National Cancer Institute.
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↵2 To whom requests for reprints should be addressed, at Medical Oncology Service, Vall d'Hebron University Hospital, Paseo Vall d'Hebrón 119–129, Barcelona 08035, Spain. Phone: 011-34-93-2746077; Fax: 011-34-93-2746059; E-mail: baselga@hg.vhebron.es.
- Received February 9, 1998.
- Accepted May 1, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 13
