Wolbachia endobacterium in wild population of Aedes albopictus (Skuse) (Diptera: Culicidae) and phylogeny from Andaman and Nicobar Islands, India.

摘要

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.