Efficacy Study of Metronomic Chemotherapy in Metastatic Triple Negative Breast Cancer and Correlation with VEGF, TSP Levels

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.