A phase II study of medroxyprogesterone acetate in patients with hormone receptor negative metastatic breast cancer: translational breast cancer research consortium trial 007
dc.contributor.author | Miller, Kathy D. | |
dc.contributor.author | Althouse, Sandra K. | |
dc.contributor.author | Nabell, Lisle | |
dc.contributor.author | Rugo, Hope | |
dc.contributor.author | Carey, Lisa | |
dc.contributor.author | Kimmick, Gretchen | |
dc.contributor.author | Jones, David R. | |
dc.contributor.author | Merino, Maria J. | |
dc.contributor.author | Steeg, Patricia S. | |
dc.contributor.department | Medicine, School of Medicine | en_US |
dc.date.accessioned | 2023-03-01T11:42:11Z | |
dc.date.available | 2023-03-01T11:42:11Z | |
dc.date.issued | 2014-11 | |
dc.description.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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Miller KD, Althouse SK, Nabell L, et al. A phase II study of medroxyprogesterone acetate in patients with hormone receptor negative metastatic breast cancer: translational breast cancer research consortium trial 007. Breast Cancer Res Treat. 2014;148(1):99-106. doi:10.1007/s10549-014-3131-3 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/31541 | |
dc.language.iso | en_US | en_US |
dc.publisher | SpringerLink | en_US |
dc.relation.isversionof | 10.1007/s10549-014-3131-3 | en_US |
dc.relation.journal | Breast Cancer Research and Treatment | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Glucocorticoid receptor | en_US |
dc.subject | Metastasis suppressor gene | en_US |
dc.subject | Angiogenesis | en_US |
dc.subject | Thrombospondin-1 | en_US |
dc.subject | Plasminogen activator inhibitor type I | en_US |
dc.title | A phase II study of medroxyprogesterone acetate in patients with hormone receptor negative metastatic breast cancer: translational breast cancer research consortium trial 007 | en_US |
dc.type | Article | en_US |