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

Kathleen E. Rodgers, Jamie Oliver, Gere S. DiZerega

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)559-568
Number of pages10
JournalCancer Chemotherapy And Pharmacology
Volume57
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

Keywords

  • Alopecia
  • Lymphopenia
  • Myelosuppression
  • Stomatitis
  • Thrombocytopenia

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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