Abstract
791 Background: Breast cancer has a significant capacity to metastisizemetastasize to bone. Bisphosphonates are the standard treatment for hypocalcaemia of malignancy (HCM), which is a common complication of bone metastasis. The combination of bisphosphonates with standard anticancer drugs like paclitaxel or tamoxifen results in a synergistic apoptotic effect greater than that produced by either single agent alone. Methods: Potential antitumour effects in vitro of two bisphosphonates: Ib and Zol (each at 30 μM) combined with different anticancer drug combinations: cyclophosphamide/metotrexate/5-fluorouracil (CMF), epirubicin/cyclophosphamide (EC), epirubicin/paclitaxel (ET), and epirubicin/ docetaxel (EDoc) have been investigated using ATP-CVA. 20 cases of female primary, invasive breast cancers have been assessed. Percentages of total growth inhibition (TGI) were calculated according to the formula: 1-(TDC-MI)/(MO-MI) x 100 = %TGI. AUC values were calculated using the trapezoidal rule. Chemosensitivity was defined as AUC of more than 18000. Statistical significance was assumed if p was < 0.05 Results: Ib and Zol alone have shown inhibitory effect on breast cancer tumour cells in vitro. BTGI effect for those two drugs amounted to 22 and 25%, respectively. Inhibitory effects were clearly visible for all four combinations of anticancer drugs together with both bisphosphonates. In all cases, the differences between measured TGI values for drugs' combinations alone in comparison to drugs with IB or Zol were statistically significant. Addition of Zol to CMF or ET revealed higher median of TGI than EC or ET plus Ib. In the lowest dose of anticancer drug concentration (6.25%), enhancing effects of Zol and Ib on TGI were clearly visible in all combinations. Addition of Zol enhanced the chemotoxic action of CMF and ET better then Ib (p= 0.03) Conclusions: Combinations of anticancer drugs with Zol seem to be more effective in respect to tumour growth inhibition than combinations with Ib, at least in case of CMF or ET in the lowest dose concentrations of those antitumour drugs. No significant financial relationships to disclose.
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