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Efficacy and safety of de-escalation bone-modifying agents for cancer patients with bone metastases: a systematic review and meta-analysis

Authors Liu C, Wang L, Liu L, Zhuang J, Tang S, Zhang TS, Zhou C, Feng F, Liu R, Zhang J, Zhang T, Gao C, Li H, Li J, Sun C

Received 10 June 2018

Accepted for publication 24 July 2018

Published 21 September 2018 Volume 2018:10 Pages 3809—3823


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Harikrishna Nakshatri

Cun Liu,1 Lu Wang,1 Lijuan Liu,2 Jing Zhuang,2 Shifeng Tang,2 Tiansong Zhang,3 Chao Zhou,2 Fubin Feng,2 Ruijuan Liu,2 Jinmei Zhang,4 Tingting Zhang,1 Chundi Gao,5 Huayao Li,5 Jia Li,6 Changgang Sun2,7

1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong Province, People’s Republic of China; 3Department of Traditional Chinese Medicine, Jing’an District Central Hospital, Shanghai, People’s Republic of China; 4Department of Endocrinology, Weifang Traditional Chinese Hospital, Weifang, Shandong, Province People’s Republic of China; 5First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 6College of Basic Medicine, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 7Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, People’s Republic of China

Background: Compared with application of bone-modifying agents (BMAs) every 4 weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy.
Methods: A systematic search of PubMed, EMBASE, and the Cochrane Register of Controlled Trials until November 22, 2017, was performed. Randomized controlled trials (RCTs) were included to assess skeletal-related event (SRE) rates, adverse events, and bone turnover biomarkers, comparing 12-weekly de-escalated treatments with standard 4-weekly dosage regimens. Risk ratios (RRs) with 95% CIs were pooled in fixed-effect meta-analyses.
Results: A total of eight citations were eligible comprising 2,878 patients: zoledronate (three studies, 2,650 patients), pamidronate (two studies, 68 patients), and denosumab (three studies, 160 patients). Summary RR (0.98; 95% CI 0.87–1.12; P=0.82) for SRE rates between de-escalated and standard arms was produced when seven low risk of bias trials (695 patients) were pooled, and results without statistical significance also appeared in the analysis of adverse events and bone turnover biomarkers. Due to the limited sample size and methodological differences, the data for skeletal morbidity rates (SMRs), time to first SRE, serum C-telopeptide (sCTx) levels, and hypocalcemia were not combined, but systematic review still obtained similar indistinguishableness.
Conclusion: In this meta-analysis of randomized clinical trials, the results “appeared” to show non-inferiority of the 12-weekly treatment. Due to the difference in available data, the results for bisphosphonates are more solid than for the receptor activator of nuclear factor-κB ligand (RANKL) antibodies.

Keywords: bone-modifying agents, bone metastasis, cancer, de-escalated treatment, meta-analysis

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