Table 3 Overview of studies investigating bisphosphonates as part of combination therapy in breast cancer
From: Anti-tumour activity of bisphosphonates in preclinical models of breast cancer
Breast cancer model | Bisphosphonate (dose) | Anti-cancer agent (dose) | Effect compared to single agent | Reference |
|---|---|---|---|---|
4TC/luc: spontaneous bone metastases | Zoledronic acid (250 μg/kg single administration) | Uracil, tegaflur (20 mg/kg/day for 7 days) | Reduced area of bone metastases | [53] |
MDA-MB-231: intracardiac injection | Zoledronic acid (0.2 μg/mouse every 2 days ×9) | Doxycycline (15 mg/kg/day for 21 days) | Reduced tumour burden in bone and in soft tissue | [54] |
B02: generates bone metastases following intravenous injection | Zoledronic acid (100 μg/kg single administration) | Doxorubicin (2 mg/kg weekly for 2 weeks) | Reduced intra-osseous tumour growth and lytic bone disease No effect on extra-osseous parts of the tumour | [48] |
MDA-MB-436: subcutaneous tumours | Zoledronic acid (100 μg/kg weekly for 6 weeks) | Doxorubicin (2 mg/kg weekly for 6 weeks) | Maximal reduction of tumour growth when doxorubicin given 24 h prior to zoledronic acid No evidence of tumours in bone | [41] |
MDA-MB-231luc: intratibial implantation | Risedronate (150 μg/kg, 5×/week) | Docetaxel (4 mg/kg, 2×/week) | Reduced tumour burden in bone and reduced osteolytic lesions | [56] |
MDA-MB-436: intratibial implantation | Zoledronic acid (100 μg/kg weekly for 6 weeks) | Doxorubicin (2 mg/kg weekly for 6 weeks) | Reduced tumour burden in bone and reduced lytic bone disease | [55] |
MDA-MB-436: subcutaneous tumours | Zoledronic acid (100 μg/kg weekly for 6 weeks) | Doxorubicin (2 mg/kg weekly for 6 weeks) | Reduced tumour growth and increased survival Sustained inhibition of tumour growth following 6 weeks of treatment | [58] |