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Cited by 115Neutropenia and Cancer InfectionsHematopoietic Stem Cell TransplantationBlood disorders and treatments

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

Rodgers, Kathleen E., Oliver, Jamie, diZerega, Gere S.·2006·Cancer Chemotherapy and Pharmacology
DOI 10.1007/s00280-005-0078-4
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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 microg/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 mug/kg per day.

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Authors
Rodgers, K. E., Oliver, J., & diZerega, G. S.
Affiliations
University of Southern California (US)
ORCID
Venue
Cancer Chemotherapy and Pharmacology
Publisher
Springer Science and Business Media LLC
Published
2005-08-12
Volume
57
Issue
5
Pages
559-568
ISSN
  • 0344-5704 (ISSN-L)
  • 1432-0843
DOI
10.1007/s00280-005-0078-4
OpenAlex
W1980946326
Cited by
115
References
41
Citations by year
2026: 4 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 6 · 2015: 14 · 2014: 4 · 2013: 7 · 2012: 10
FWCI
1.09
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Cancer Chemotherapy and Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
Keywords
angiotensin-(1-7), breast cancer, chemotherapy-induced myelosuppression, hematopoietic growth factors, thrombocytopenia, lymphopenia, anemia, filgrastim, dose escalation, maximum tolerated dose, multilineage hematopoiesis, bone marrow progenitor cells
MeSH terms
Adult, Aged, Angiotensin I, Antihypertensive Agents, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cyclophosphamide, Dose-Response Relationship, Drug, Doxorubicin, Female, Humans, Middle Aged, Peptide Fragments, Prospective Studies, Maximum Tolerated Dose

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