TY - JOUR
T1 - Emerging role of bisphosphonates in the clinic-Antitumor activity and prevention of metastasis to bone
AU - Lipton, Allan
PY - 2008/5/16
Y1 - 2008/5/16
N2 - Bisphosphonates are currently used for the treatment of bone metastases, and emerging data suggest that they may also have antitumor properties. Preclinical studies have demonstrated that zoledronic acid can inhibit angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, and emerging evidence suggests that the use of these agents may impede the development of skeletal metastases. In a recent clinical study in patients with metastatic bone disease, basal levels of vascular endothelial growth factor, a factor essential for angiogenesis, were significantly reduced in patients receiving zoledronic acid, suggesting that zoledronic acid may have clinically relevant antiangiogenic properties. Early clinical data on prevention of bone metastases by the early-generation bisphosphonate clodronate have yielded promising results in patients with breast cancer, and trials are currently ongoing to assess the efficacy of clodronate in this setting. Similarly, the new-generation bisphosphonate zoledronic acid has demonstrated activity in the prevention of bone metastases in small, 18-month pilot studies in patients with high-risk solid tumors (N = 40; P = 0.0002). Similarly, in a separate 5-year trial, the overall survival of patients with multiple myeloma was greater in patients whose standard treatment regimens included zoledronic acid compared with standard treatment alone (P < 0.01). These encouraging early clinical results supported the initiation of larger randomized trials that are currently ongoing.
AB - Bisphosphonates are currently used for the treatment of bone metastases, and emerging data suggest that they may also have antitumor properties. Preclinical studies have demonstrated that zoledronic acid can inhibit angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, and emerging evidence suggests that the use of these agents may impede the development of skeletal metastases. In a recent clinical study in patients with metastatic bone disease, basal levels of vascular endothelial growth factor, a factor essential for angiogenesis, were significantly reduced in patients receiving zoledronic acid, suggesting that zoledronic acid may have clinically relevant antiangiogenic properties. Early clinical data on prevention of bone metastases by the early-generation bisphosphonate clodronate have yielded promising results in patients with breast cancer, and trials are currently ongoing to assess the efficacy of clodronate in this setting. Similarly, the new-generation bisphosphonate zoledronic acid has demonstrated activity in the prevention of bone metastases in small, 18-month pilot studies in patients with high-risk solid tumors (N = 40; P = 0.0002). Similarly, in a separate 5-year trial, the overall survival of patients with multiple myeloma was greater in patients whose standard treatment regimens included zoledronic acid compared with standard treatment alone (P < 0.01). These encouraging early clinical results supported the initiation of larger randomized trials that are currently ongoing.
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U2 - 10.1016/j.ctrv.2008.03.008
DO - 10.1016/j.ctrv.2008.03.008
M3 - Review article
C2 - 18486347
AN - SCOPUS:44649087001
SN - 0305-7372
VL - 34
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
IS - SUPPL. 1
ER -