Metronomic chemotherapy in metastatic breast cancer: impact on VEGF.

Background: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents; including cyclophosphamide (CTX) and capecitabine (Cap) when given at lower doses for prolonged period (metronomic chemotherapy) postulating an antiangiogenic activity as well.

Aim Of Work: To evaluate the action and tolerability of metronomic chemotherapy (MC) and its impact on serum vascular endothelial growth factor (VEGF) levels in metastatic breast cancer (MBC) patients.

Patients And Methods: In this study we evaluated the clinical efficacy and tolerability of low dose, capecitabine (500mg twice daily) together with oral cyclophosphamide (CTX) (a dose of 50mg once daily) in patients with metastatic breast cancer. Vascular endothelial growth factor (VEGF), an angiogenic marker, was measured in the serum samples; at base line, and after 2 and 6months of therapy.

Results: Sixty patients were evaluable. One achieved complete response (CR), 12 partial responses (PR), and 21 stable diseases (SD), while 26 were with progressive disease (PD). The overall response rate was 21.7% with overall disease control (CR, PR, and SD) 56.7%. The median time to progression was 7±2.59months and overall survival 16±8.02months. Toxicity was mild, Palmar-plantar erythrodythesia was the most common side effect and was observed in 22 patients (37%), leucopenia (G1+2) was the most common hematological toxicity, and it was reported in 27% of the cases. The median VEGF level was significantly declined after 2 and 6months of therapy compared to the base line among the patients with disease control (CR, PR, and SD). In multivariate logistic regression analysis, patients with post-menopausal, positive hormonal receptors, negative HER-2/Neu, and one metastatic site, were statistically significant and have a better disease control rate.

Conclusions: MC induced drop in VEGF, and was effective, minimally toxic regimen for the treatment of metastatic breast cancer patients.