Efficacy and Safety of Zoledronic Acid and Pamidronate Disodium in the Treatment of Malignant Skeletal Metastasis

Solid tumors frequently metastasize to bone. Two bisphosphonates have been investigated for bone metastases including pamidronate disodium and zoledronic acid. By searching the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases, we conducted a metaanalysis to determine the efficacy and safety of zoledronic acid compared with pamidronate disodium in reducing pain in patients with bone metastases. Studies were pooled, and the relative risk (RR) and its corresponding 95 % confidence interval (CI) were calculated. Version 12.0 STATA software was used for statistical analysis. Twenty relevant articles were included for this meta-analysis study. The complete response rate in cancer patients treatment with zoledronic acid was significantly higher than that with pamidronate disodium (relative risk [RR]1⁄4 1.32 [95% confidence interval (CI), 1.00–1.75]; P1⁄4 0.987, I1⁄4 0%). However, there was no significant difference in the rate of partial response rate (RR1⁄4 1.04, 95% CI: 0.90– 1.20; P1⁄4 0.942, I1⁄4 0%) and in the total effective rate (RR1⁄4 1.06, 95% CI: 1.00–1.12; P1⁄4 0.998, I1⁄4 0%). For adverse events (AE), the incidence of headache in cancer patients with zoledronic acid was significantly lower than that with pamidronate disodium (RR1⁄4 0.82, 95% CI: 0.70–0.96; P1⁄4 0.793, I1⁄4 0%). There was no significant difference in nausea or vomiting (RR1⁄4 1.00, 95% CI: 0.92–1.09; P1⁄4 0.494, I1⁄4 0%), fever (RR1⁄4 0.98, 95% CI: 0.85–1.14; P1⁄4 0.633, I1⁄4 0%), fatigue (RR1⁄4 1.01, 95% CI: 0.91–1.11; P1⁄4 0.914, I1⁄4 0%) and anorexia (RR1⁄4 1.31, 95% CI: 0.91–1.87; P1⁄4 0.024, I1⁄4 64.4%). In conclusion, this meta-analysis indicates that treatment with zoledronic acid was more effective than pamidronate disodium in the complete response assessments and the incidence of headache, an AE, was significantly lower in cancer patients with zoledronic acid. (Medicine 94(42):e1822) INTRODUCTION d Shuai Du affected by skeletal metastases in the world. Advanced cancer patients with bone metastases are common, 100% of myeloma patients, 70% to 80% of prostate or breast cancer patients and 30% to 40% of lung cancer or other solid tumors. In patients with bone metastases there is an increased risk of skeletalrelated events (SREs) such as bone pain, pathologic fractures, impaired mobility, spinal cord compression, surgery or palliative radiotherapy, hypercalcemia. These SREs can limit patients’ functional independence and undermine their quality of life and place a heavy burden on affected patients and on the healthcare system. The main mechanism of bone metastasis is the activation of osteoclasts and bone-derived growth factor, which is induced by tumor cells to stimulate tumor growth. Current treatment of bone metastases in patients includes surgery, radiation therapy, bisphosphonate drugs, and painkillers, in addition to standard anticancer therapies. The main goal of treatment is to reduce the incidence of bone pain and improve quality of life and mobility. Bisphosphonates are osteoclast-mediated bone resorption potent inhibitor. Bisphosphonates has adopted a number of clinical trials in osteoclast activation of diseases, such as osteoporosis, hypercalcemia of malignancy, Paget’s disease, and bone metastases. Pamidronate was approved by the US FDA in 1996 for treatment of skeletal metastases resulting from breast cancer and multiple myeloma (MM), and for Paget’s disease of bone, and hypercalcemia of malignancy. Zoledronic acid was approved in 2002 in the United States for treatment of skeletal metastases caused by MM and solid tumors including lung cancer, prostate cancer, metastatic breast cancer (MBC), renal cancer, and colorectal cancer among others, after the benefits were noted. In this study, we performed a meta-analysis to assess the efficacy and safety of zoledronic acid and pamidronate disodium among patients with metastatic bone disease. MATERIALS AND METHODS