A phase II study of medroxyprogesterone acetate in patients with hormone receptor negative metastatic breast cancer: translational breast cancer research consortium trial 007

Kathy D. Miller, Sandra K. Althouse, Lisle Nabell, Hope Rugo, Lisa Carey, Gretchen Kimmick, David R. Jones, Maria J. Merino, Patricia S. Steeg

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Preclinical data suggest that medroxyprogesterone acetate (MPA) has both anti-metastatic and anti-angiogenic activity in the absence of hormone receptors (HR). This phase II trial assessed the activity of MPA alone or in combination with low-dose chemotherapy in patients with metastatic HR-negative breast cancer. Postmenopausal women with HR-negative disease were eligible if they had not received more than 3 chemotherapy regimens for metastatic disease. All patients were treated with MPA 1,000–1,500 mg/day orally; patients in cohort two also received low-dose oral cyclophosphamide and methotrexate (ldCM, 50 mg/day and 2.5 mg twice daily on Days 1 and 2 each week). Tissue and circulating biomarkers were assessed serially. The primary endpoint was clinical benefit response defined as objective response or stable disease >6 months. Thirty patients were enrolled (14 MPA monotherapy; 16 MPA + ldCM); median age was 55 (35–80); nearly all had visceral involvement. Despite dose escalation in 90 % of patients, only 17 (57 %) patients ever achieved MPA trough concentrations >50 ng/ml. One patient developed grade 4 renal failure in the setting of rapid disease progression and dehydration. There were no objective responses. One patient in each cohort (~7 %) had stable disease for > 6 months. Skin Nm23 expression increased after 4 weeks of MPA + ldCM, but there were no significant changes in TSP-1, PAI-1 antigen, or PAI-1 activity. MPA had limited activity and does not warrant further development in patients with HR-negative advanced breast cancer. Poor bioavailability limited exposure despite dose escalation.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalBreast Cancer Research and Treatment
Volume148
Issue number1
DOIs
StatePublished - Oct 14 2014

Keywords

  • Angiogenesis
  • Glucocorticoid receptor
  • Metastasis suppressor gene
  • Nm023
  • Plasminogen activator inhibitor type I
  • Thrombospondin-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

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