Back
 ABCR  Vol.7 No.2 , April 2018
Efficacy Study of Metronomic Chemotherapy in Metastatic Triple Negative Breast Cancer and Correlation with VEGF, TSP Levels
Abstract: Background: Treatment refractory metastatic breast cancer patients are at best treated palliatively. We evaluated the effects of metronomic chemotherapy on survival outcomes in this population. Methods: Twenty eight subjects with treatment refractory (n = 21) and treatment naive (n = 7) MBC were included in an open label single arm efficacy study of metronomic chemotherapy. Patients were given a chemotherapy regimen of Tab. Cyclophosphamide 50 mg once daily and Tab. Methotrexate 2.5 mg twice in a week over a minimum period of 3 months or until the progression of their disease whichever was earlier. Monitoring of serum VEGF and Thrombospondin levels were done to correlate the response rates. Data were analysed using chi square test for proportions and Kaplan Meir Survival analysis. Results: The mean age of the study population was 51.5 ± 14.2 years. The mean duration of metronomic chemotherapy was 123.89 ± 97.6 days. Overall 71.4% had progressive disease and 28.6% had stable disease. 55.6% with treatment naive metastatic breast cancer had stable disease compared to 15.8% of treatment refractory metastatic breast cancer. There was also a significant improvement in progression free survival in those with tumor load less than 5 cms compared to >5 cms and in grade 2 compared to grade 3 disease. There was no correlation of serum VEGF levels before and after chemotherapy. There is no significant decrease in TSP levels. Conclusion: The results suggest stable response in one third of study patients. Performance status and tumor load are important predictors in this category of population. There is no significant correlation of serum VEGF and TSP levels before and after chemotherapy. Also, there was no significant correlation of biomarker levels in responding and non-responding patients.
Cite this paper: Srinivasa, B. , Bhanu, L. , Veldore, V. , Raghavendra, R. and Naik, R. (2018) Efficacy Study of Metronomic Chemotherapy in Metastatic Triple Negative Breast Cancer and Correlation with VEGF, TSP Levels. Advances in Breast Cancer Research, 7, 107-119. doi: 10.4236/abcr.2018.72007.
References

[1]   André, N., Banavali, S., Snihur, Y. and Pasquier, E. (2013) Has the Time Come for Metronomics in Low-Income and Middle-Income Countries? The Lancet Oncology, 14, e239.
https://doi.org/10.1016/S1470-2045(13)70056-1

[2]   Pasquier, E., Kavallaris, M. and André, N. (2010) Metronomic Chemotherapy: New Rationale for New Directions. Nature Reviews Clinical Oncology, 7, 455-465.
https://doi.org/10.1038/nrclinonc.2010.82

[3]   Browder, T., Butterfield, C.E., Kraling, B.M., Shi, B., Marshall, B., O’Reilly, M.S., et al. (2000) Antiangiogenic Scheduling of Chemotherapy Improves Efficacy against Experimental Drug-Resistant Cancer. Cancer Research, 60, 1878-1786.

[4]   Klement, G., Huang, P., Mayer, B., Green, S.K., Man, S., Bohlen, P., Hicklin, D. and Kerbel, R.S. (2002) Differences in Therapeutic Indexes of Combination Metronomic Chemotherapy and Anti-VEGFR-2 Antibody in Multidrug-Resistant Human Breast Cancer Xenografts. Clinical Cancer Research, 8, 221-232.

[5]   Man, S., Bocci, G., Francia, G., Green, S.K., Jothy, S., Hanahan, D., et al. (2002) Antitumor Effects in Mice of Low-Dose (Metronomic) Cyclophosphamide Administered Continuously through the Drinking Water. Cancer Research, 62, 2731-2735.

[6]   Colleoni, M., Rocca, A., Sandri, M.T., Zorzino, L., Masci, G., Nolè, F., et al. (2002) Low-Dose Oral Methotrexate and Cyclophosphamide in Metastatic Breast Cancer: Antitumor Activity and Correlation with Vascular Endothelial Growth Factor Levels. Annals of Oncology, 13, 73-80.
https://doi.org/10.1093/annonc/mdf013

[7]   Colleoni, M., Orlando, L., Sanna, G., Rocca, A., Maisonneuve, P., Peruzzotti, G., et al. (2006) Metronomic Low-Dose Oral Cyclophosphamide and Methotrexate Plus or Minus Thalidomide in Metastatic Breast Cancer: Antitumor Activity and Biological Effects. Annals of Oncology, 17, 232-238.
https://doi.org/10.1093/annonc/mdj066

[8]   Orlando, L., Cardillo, A., Rocca, A., Balduzzi, A., Ghisini, R., Peruzzotti, G., et al. (2006) Prolonged Clinical Benefit with Metronomic Chemotherapy in Patients with Metastatic Breast Cancer. Anticancer Drugs, 17, 961-967.
https://doi.org/10.1097/01.cad.0000224454.46824.fc

[9]   Hirata, S., Matsubara, T., Saura, R., Tateishi, H. and Hirohata, K. (1989) Inhibition of In Vitro Vascular Endothelial Cell Proliferation and In Vivo Neovascularization by Low Dose Methotrexate. Arthritis & Rheumatology, 32, 1065-1073.
https://doi.org/10.1002/anr.1780320903

[10]   Kaplan, H.G. and Malmgren, J.A. (2008) Impact of Triple Negative Phenotype on Breast Cancer Prognosis. The Breast Journal, 14, 456-463.
https://doi.org/10.1111/j.1524-4741.2008.00622.x

[11]   Livasy, C.A., Karaca, G., Nanda, R., Tretiakova, M.S., Olopade, O.I., Moore, D.T., et al. (2006) Phenotypic Evaluation of the Basal-Like Subtype of Invasive Breast Carcinoma. Modern Pathology, 19, 264-271.
https://doi.org/10.1038/modpathol.3800528

[12]   Anders, C.K. and Carey, L.A. (2013) Epidemiology, Risk Factors and the Clinical Approach to ER/PR Negative, HER2-Negative (Triple-Negative) Breast Cancer (Online).
http://www.uptodate.com/contents/epidemiology

[13]   DeVita Jr, V.T., Lawrence, T.S. and Rosenberg, S.A., Eds. (2011) Cancer Principles and Practice of Oncology. 9th Edition, Lippincott Williams & Wilkins, USA, 799, 814, 843.

[14]   Groome, P.A., Bolejack, V., Crowley, J.J., Kennedy, C., Krasnik, M., Sobin, L.H., et al. (2007) The IASLC Lung Cancer Staging Project: Validation of the Proposals for Revision of the T, N, and M Descriptors and Consequent Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours. Journal of Thoracic Oncology, 2, 694-705.
https://doi.org/10.1097/JTO.0b013e31812d05d5

[15]   Eisenhauer, E.A., Therasse, P., Bogaerts, J., Schwartz, L.H., Sargent, D., Ford, R., et al. (2009) New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (Version 1.1). European Journal of Cancer, 45, 228-247.
https://doi.org/10.1016/j.ejca.2008.10.026

[16]   U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute (2009) Common Terminology Criteria for Adverse Events (CTCAE) (v4.02: S).

 
 
Top