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Phase I/II dose escalation study of angiotensin 1-7 [A(1-7)] administered before and after chemotherapy in patients with newly diagnosed breast cancer

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Abstract

Purpose: Multilineage cytopenias occur following myelosuppressive chemotherapy. Most hematopoietic agents differentiate along a single lineage and fail to prevent progressive cytopenias. Angiotensin 1-7 [A(1-7)] is a hematopoietic agent that stimulates the proliferation of multipotential and differentiated progenitor cells in cultured bone marrow and human cord blood. The purpose of this study was to determine the optimal biologic dose and the maximum tolerated dose of A(1-7). Experimental design: This study determined the safety and activity of A(1-7) following chemotherapy in patients with breast cancer. Toxicity was assessed by administering A(1-7) daily for 7 days followed by a 7-day washout prior to the first cycle of chemotherapy. Beginning 2 days after chemotherapy and continuing daily for at least 10 days, fifteen patients received five different A(1-7) doses and five patients received filgrastim as a comparator group over three cycles of chemotherapy. Results: No dose-limiting toxicity was observed following A(1-7). The frequency of adverse events was slightly lower in A(1-7) than in filgrastim patients. No patient required a chemotherapy modification due to hematologic toxicity. There was an apparent differential dose-response sensitivity of the various lineages to A(1-7). At a dose of 100 μg/kg, A(1-7) reduced the frequency of grade 2–4 thrombocytopenia, anemia, and grade 3–4 lymphopenia as compared to filgrastim. Conclusion: These data suggest that A(1-7) may be beneficial in attenuating multilineage cytopenias following chemotherapy at a dose of 100 μg/kg per day.

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Acknowledgement

The authors would like to acknowledge the editorial assistance of Laura dizerega in the development of this paper.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Livingston Reproductive Biology Laboratories, University of Southern California Keck School of Medicine, 1321 North Mission Road, Los Angeles, CA, 90033, USA

    Kathleen E. Rodgers & Gere S. diZerega

  2. Ockham Development Group, 2000 Regency Parkway, Suite 315, Cary, NC, 27511, USA

    Jamie Oliver

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  1. Kathleen E. Rodgers
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  2. Jamie Oliver
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  3. Gere S. diZerega
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Rodgers, K.E., Oliver, J. & diZerega, G.S. Phase I/II dose escalation study of angiotensin 1-7 [A(1-7)] administered before and after chemotherapy in patients with newly diagnosed breast cancer. Cancer Chemother Pharmacol 57, 559–568 (2006). https://doi.org/10.1007/s00280-005-0078-4

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