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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Miller, KD; Althouse, SK; Nabell, L; Rugo, H; Carey, L; Kimmick, G; Jones, DR; Merino, MJ; Steeg, PS

Published Date

  • November 2014

Published In

Volume / Issue

  • 148 / 1

Start / End Page

  • 99 - 106

PubMed ID

  • 25257727

Pubmed Central ID

  • PMC8374454

Electronic International Standard Serial Number (EISSN)

  • 1573-7217

Digital Object Identifier (DOI)

  • 10.1007/s10549-014-3131-3


  • eng

Conference Location

  • Netherlands