Zoledronic acid use in cancer patients

Abstract

Bone is the most common site for metastasis from solid tumors, and the majority of patients will develop bone metastases during the natural course of their disease. Bisphosphonates are an effective treatment for preventing skeletal-related events in patients with bone metastases and may preserve functional independence and quality of life. Although several bisphosphonates have been investigated in patients with solid tumors, only zoledronic acid (ZOL) is approved by the US Food and Drug Administration and the European Medicines Agency for preventing skeletalrelated events in patients across a broad range of solid tumors. In addition, bisphosphonates, notably ZOL, prevent cancer treatment-induced bone loss in breast and prostate cancer patients who are receiving endocrine therapy. It also has been demonstrated that ZOL directly and indirectly inhibits cancer cell growth in vitro and growth and tumorigenesis in animal model systems. These properties may produce clinically meaningful benefits. In recent clinical studies in patients with cancer, ZOL improved overall and prolonged disease-free survival. Ongoing clinical trials in patients with solid tumors will provide further insight into the potential of ZOL to prevent distant metastases and improve survival. Cancer 2011;117:11-23. V C 2010 American Cancer Society.KEYWORDS: adjuvant setting, bisphosphonate, bone metastases, cancer, survival, zoledronic acid.During the progression of cancer, many patients will develop distant metastases, for which a common site is bone. 1For example, an estimated 75% of patients with advanced breast cancer (BC) or prostate cancer (PC), and 40% of patients with advanced lung cancer (LC) develop bone metastases.2,3 Without bone-targeted therapies, most patients with bone metastases will experience potentially debilitating skeletal-related events (SREs), such as pathologic fractures, spinal cord compression, the need for surgery or palliative radiotherapy to bone, or hypercalcemia of malignancy.1 These SREs can have debilitating consequences and reduce quality of life and survival. 4 Moreover, declines in performance status resulting from SREs could preclude the receipt of chemotherapy and radiotherapy by patients with some solid tumors. 5Bisphosphonates, which are inhibitors of osteoclast-mediated bone resorption, currently are the standard of care for preventing SREs in patients with bone metastases.6 Several bisphosphonates currently are approved by the US Food and Drug Administration and the European Medicines Agency for preventing SREs in patients with metastatic BC and multiple myeloma (MM). In addition, the nitrogen-containing bisphosphonate (N-BP) zoledronic acid (ZOL) has received widespread regulatory approval for patients with bone involvement from PC, LC, and the entire range of other solid tumors (OSTs). 6 In randomized phase 3 trials, ZOL (4 mg intravenously [iv] every 3 to 4 weeks [monthly]) demonstrated significant efficacy in delaying the onset and reducing the risk of SREs and in palliating bone pain, reducing analges...

Evaluation of safety and analgesic consumption in patients with advanced cancer treated with zoledronic acid

“…Adverse events were mainly associated with the primary disease and most cannot be directly linked to zoledronic acid therapy. PSA in prostate cancer patients as a group remained unchanged or even decreased during the observation period which may indirectly support reports of zoledronic acid anticancer activity 20,21…”

Bone-Derived IGF Mediates Crosstalk between Bone and Breast Cancer Cells in Bony Metastases

“…However, we observed discernible increase in calvarial bone formation probably as a consequence of IL-1β-stimulated bone resorption as described in the previous report (27). IL-1β administered together with the BP ZOL, a potent and specific inhibitor of osteoclastic bone resorption (5), showed significant reduction of osteolytic bone metastases on calvarial bones (Figure 1C). ZOL alone with no IL-1β injections, followed by intracardiac inoculation of MDA-MB-231 cells showed no effects on calvarial bones, since no osteolytic bone metastases were developed on the calvarial bones in the absence of IL-1β injections.…”

“…Bone metastasis represents one of the major causes of morbidity such as intractable bone pain, pathological fractures, spinal cord compression, and hypercalcemia in cancer patients. Accumulated clinical and experimental data that specific inhibitors of osteoclasts including bisphosphonates (BPs) effectively suppress osteolytic bone metastases (4, 5) suggest that osteoclastic bone destruction plays a critical role in the development and progression of bone metastases.…”

Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications

“…They might help to maintain functional independence and quality of life [175]. Several BPs have shown some efficacy in this regard, but owing to its easy mode of administration and its potency, zoledronic acid became the most used drug.…”