Abstract
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 ≥ 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.
| Original language | English |
|---|---|
| Pages (from-to) | 723-730 |
| Number of pages | 8 |
| Journal | Journal of Clinical Oncology |
| Volume | 28 |
| Issue number | 5 |
| DOIs | |
| State | Published - Feb 10 2010 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Medicine(all)
Cite this
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. / Wong, Nan Soon; Buckman, Robert A.; Clemons, Mark; Verma, Shailendra; Dent, Susan; Trudeau, Maureen E.; Roche, Kathie; Ebos, John; Kerbel, Robert; DeBoer, Gerrit E.; Sutherland, Donald J A; Emmenegger, Urban; Slingerland, Joyce M; Gardner, Sandra; Pritchard, Kathleen I.
In: Journal of Clinical Oncology, Vol. 28, No. 5, 10.02.2010, p. 723-730.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Wong, Nan Soon
AU - Buckman, Robert A.
AU - Clemons, Mark
AU - Verma, Shailendra
AU - Dent, Susan
AU - Trudeau, Maureen E.
AU - Roche, Kathie
AU - Ebos, John
AU - Kerbel, Robert
AU - DeBoer, Gerrit E.
AU - Sutherland, Donald J A
AU - Emmenegger, Urban
AU - Slingerland, Joyce M
AU - Gardner, Sandra
AU - Pritchard, Kathleen I.
PY - 2010/2/10
Y1 - 2010/2/10
N2 - 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 ≥ 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.
AB - 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 ≥ 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.
UR - http://www.scopus.com/inward/record.url?scp=77649221837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649221837&partnerID=8YFLogxK
U2 - 10.1200/JCO.2009.24.0143
DO - 10.1200/JCO.2009.24.0143
M3 - Article
VL - 28
SP - 723
EP - 730
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 5
ER -