PMID- 31475116
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231013
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 9
DP  - 2019
TI  - Is De-escalated Bisphosphonates Therapy a Suitable Alternative to Standard Dosing 
      in Malignant Tumor Patients With Bone Metastases: A Systematic Review and 
      Meta-Analysis.
PG  - 774
LID - 10.3389/fonc.2019.00774 [doi]
LID - 774
AB  - Background: Previous studies have preliminarily identified the non-inferior 
      efficacy for reducing skeletal-related event (SRE) rates between de-escalated 
      (Q12w) and standard (Q3-4w) bone-targeting agents therapy in malignant tumor 
      patients with bone metastases. In this study, we aim to make further efforts to 
      analyze whether the de-escalated bisphosphonates (BPs) strategy is a suitable 
      option by comprehensively retrieving and synthesizing state-of-the-art evidence. 
      Methods: An extensive electronic search for randomized controlled trials (RCTs) 
      comparing a BPs standard strategy with the de-escalated one in patients with bone 
      metastases was performed up to June 2018. Outcomes of interest were general and 
      found individual types of SRE, skeletal morbidity rate (SMR), bone pain, bone 
      turnover biomarkers and adverse events (AEs). Continuous and dichotomous outcomes 
      were summarized by the weighted mean difference (WMD) and risk ratio (RR), 
      respectively, with 95% confidence intervals (CIs). Results: A total of eight 
      studies, representing six unique trials (involving 3114 patients), were included. 
      Pooled results indicated comparable efficacy on general SRE (RR 0.99, 95% CI 
      0.87-1.12; P = 0.86; I (2) = 0%) and SMR (WMD 0.00, 95% CI -0.02 -0.03; P = 0.81; 
      I (2) = 0%). However, the rate of surgery involving bones was significantly 
      higher in de-escalated group than standard group (RR 1.92, 95% CI 1.17-3.15; P = 
      0.01; I (2) = 0%) among individual types of SRE. Several trials also demonstrated 
      increased levels of C-terminal or N-terminal telopeptide in de-escalated group. 
      Meta-analyses for gastrointestinal disorders, dizziness and back pain showed 
      significant reductions by 27% (RR 0.73, 95% CI 0.57-0.94; P = 0.01; I (2) = 0%), 
      48% (RR 0.52 95% CI 0.32-0.86; P = 0.01; I (2) = 0%), and 29% (RR 0.71, 
      0.51-0.99; P = 0.04; I (2) = 0%), respectively, compared to the standard therapy. 
      Conclusion: For malignant tumor patients with bone metastases, a de-escalated BPs 
      strategy is proved to have a better safety profile compared to standard dosing. 
      Although the efficacy is generally comparable on SRE and SMR between the two 
      dosing regimens, trials with long duration and large sample sizes are still 
      warranted to make a solid judgment.
FAU - Luo, Qiuhua
AU  - Luo Q
AD  - Department of Pharmacy, The First Affiliated Hospital of China Medical 
      University, Shenyang, China.
FAU - Men, Peng
AU  - Men P
AD  - Department of Pharmacy, Peking University Third Hospital, Beijing, China.
FAU - Liu, Zhiyong
AU  - Liu Z
AD  - Liaoning Center for Drug and Device Evaluation and Monitoring, Shenyang, China.
FAU - Zhai, Suodi
AU  - Zhai S
AD  - Department of Pharmacy, Peking University Third Hospital, Beijing, China.
FAU - Jiang, Mingyan
AU  - Jiang M
AD  - Department of Pharmacy, The First Affiliated Hospital of China Medical 
      University, Shenyang, China.
LA  - eng
PT  - Systematic Review
DEP - 20190814
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC6702312
OTO - NOTNLM
OT  - ONJ (osteonecrosis of the jaws)
OT  - adverse effect
OT  - bisphosphonates
OT  - bone metastases
OT  - de-escalated therapy
EDAT- 2019/09/03 06:00
MHDA- 2019/09/03 06:01
PMCR- 2019/01/01
CRDT- 2019/09/03 06:00
PHST- 2019/03/04 00:00 [received]
PHST- 2019/07/31 00:00 [accepted]
PHST- 2019/09/03 06:00 [entrez]
PHST- 2019/09/03 06:00 [pubmed]
PHST- 2019/09/03 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2019.00774 [doi]
PST - epublish
SO  - Front Oncol. 2019 Aug 14;9:774. doi: 10.3389/fonc.2019.00774. eCollection 2019.