{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:37:20Z","timestamp":1773146240891,"version":"3.50.1"},"reference-count":45,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2010,2,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Preclinical studies indicate that metronomic chemotherapy is antiangiogenic and synergistic with other antiangiogenic agents. We designed a phase I\/II study to evaluate the safety and activity of adding dalteparin and prednisone to metronomic cyclophosphamide and methotrexate in women with measurable metastatic breast cancer (MBC). <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Patients received daily dalteparin and oral cyclophosphamide, twice-weekly methotrexate, and daily prednisone (dalCMP). The primary study end point was clinical benefit rate (CBR), a combination of complete response (CR), partial response (PR), and prolonged stable disease for \u2265 24 weeks (pSD). Secondary end points included time to progression (TTP), duration of response, and overall survival (OS). Biomarker response to treatment was assessed by using plasma vascular endothelial growth factor (VEGF) and soluble VEGF receptors (sVEGFRs) \u20131 and \u20132. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Forty-one eligible patients were accrued. Sixteen (39%) had no prior chemotherapy for MBC; 15 (37%) had two or more chemotherapy regimens for MBC. Toxicities were minimal except for transient grade 3 elevation of liver transaminases in 11 patients (27%) and grade 3 vomiting in one patient (2%). One patient (2%) had CR, six (15%) had PR, and three (7%) had pSD, for a CBR of 10 (24%) of 41 patients. Median TTP was 10 weeks (95% CI, 8 to 17 weeks), and median OS was 48 weeks (95% CI, 32 to 79 weeks). VEGF levels decreased but not significantly, whereas sVEGFR-1 and -2 levels increased significantly after 2 weeks of therapy. There was no correlation between response and VEGF, sVEGFR-1, or sVEGFR-2 levels. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Metronomic dalCMP is safe, well tolerated, and clinically active in MBC. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2009.24.0143","type":"journal-article","created":{"date-parts":[[2009,12,22]],"date-time":"2009-12-22T02:42:51Z","timestamp":1261449771000},"page":"723-730","source":"Crossref","is-referenced-by-count":68,"title":["Phase I\/II Trial of Metronomic Chemotherapy With Daily Dalteparin and Cyclophosphamide, Twice-Weekly Methotrexate, and Daily Prednisone As Therapy for Metastatic Breast Cancer Using Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor Levels As Markers of Response"],"prefix":"10.1200","volume":"28","author":[{"given":"Nan Soon","family":"Wong","sequence":"first","affiliation":[{"name":"From the Sunnybrook Odette Cancer Centre, University of Toronto, Toronto; 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