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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.

Publication ,  Journal Article
Wong, NS; Buckman, RA; Clemons, M; Verma, S; Dent, S; Trudeau, ME; Roche, K; Ebos, J; Kerbel, R; Deboer, GE; Sutherland, DJA; Emmenegger, U ...
Published in: J Clin Oncol
February 10, 2010

PURPOSE 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). PATIENTS AND METHODS 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 > or = 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) -1 and -2. Results 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. CONCLUSION Metronomic dalCMP is safe, well tolerated, and clinically active in MBC.

Duke Scholars

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

February 10, 2010

Volume

28

Issue

5

Start / End Page

723 / 730

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor A
  • Treatment Outcome
  • Time Factors
  • Prednisone
  • Ontario
  • Oncology & Carcinogenesis
  • Middle Aged
  • Methotrexate
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wong, Nan Soon, Robert A. Buckman, Mark Clemons, Shailendra Verma, Susan Dent, Maureen E. Trudeau, Kathie Roche, et al. “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.J Clin Oncol 28, no. 5 (February 10, 2010): 723–30. https://doi.org/10.1200/JCO.2009.24.0143.
Wong NS, Buckman RA, Clemons M, Verma S, Dent S, Trudeau ME, Roche K, Ebos J, Kerbel R, Deboer GE, Sutherland DJA, Emmenegger U, Slingerland J, Gardner S, Pritchard KI. 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. J Clin Oncol. 2010 Feb 10;28(5):723–730.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

February 10, 2010

Volume

28

Issue

5

Start / End Page

723 / 730

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor A
  • Treatment Outcome
  • Time Factors
  • Prednisone
  • Ontario
  • Oncology & Carcinogenesis
  • Middle Aged
  • Methotrexate