Systematic review and meta-analysis comparing zoledronic acid administered at 12-week and 4-week intervals in patients with bone metastasis
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Ling Cao1,*, Yong-Jing Yang1,*, Jian-Dong Diao2, Xu-He Zhang1, Yan-Ling Liu1, Bo-Yu Wang1, Zhi-Wen Li3 and Shi-Xin Liu1
1Department of Radiation Oncology, Cancer Hospital of Jilin Province, Changchun 130012, People’s Republic of China
2Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun 130012, People’s Republic of China
3Department of Anesthesiology, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
*These authors contributed equally to this work
Shi-Xin Liu, email: [email protected]
Zhi-Wen Li, email: [email protected]
Keywords: zoledronic acid, bone metastasis, dose interval, skeletal-related events, meta-analysis
Received: April 21, 2017 Accepted: July 18, 2017 Published: August 03, 2017
Zoledronic acid is used to treat patients with bone metastasis, but the optimal dosing interval remains controversial. We therefore performed a systematic review and meta-analysis to compare the efficacy and safety of a 12-week interval of zoledronic acid with the standard 4-week interval. Three randomized controlled trials comprising 2650 patients were analyzed. Using a random-effects model, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. No differences in the occurrence of skeletal-related events (SREs: RR = 0.98; 95% CI = 0.86–1.12; P = 0.80) or grade 3/4 adverse events (RR = 0.91; 95% CI = 0.69–1.20; P = 0.52) were observed between the 12-week and 4-week groups. The 12-week group tended to have lower incidences of osteonecrosis of the jaw [13 (0.98%) vs. 23 (1.73%)] and kidney dysfunction [21 (1.68%) vs. 31 (2.45%)] than the 4-week group, though the difference did not reach statistical significance (RR = 0.58, 95% CI: 0.30–1.12; P = 0.11); (RR = 0.67, 95% CI: 0.39–1.15, P = 0.15). These data show that zoledronic acid administered at 12-week intervals instead of 4-week intervals does not increase the risk of SREs, and may reduce the incidence of osteonecrosis of the jaw and kidney dysfunction. This suggests the 12-week interval with zoledronic acid may be an acceptable treatment option.
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