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

Academic Article


  • © 2014, Springer Science+Business Media New York. 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.
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    Digital Object Identifier (doi)

    Author List

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

  • 99
  • End Page

  • 106
  • Volume

  • 148
  • Issue

  • 1