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Bisphosphonates in the treatment of patients with lung cancer and metastatic bone disease: a systematic review and meta-analysis.

ABSTRACT: Bisphosphonates are known to prevent skeletal-related events (SREs) in advanced breast cancer, prostate cancer, and multiple myeloma. This systematic review assessed the efficacy of bisphosphonates in preventing SREs, controlling pain, and overall survival in patients with bone metastases from lung cancer.We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Library databases through November 10, 2011 for controlled trials that included lung cancer patients with bone metastases treated with bisphosphonates. Two reviewers independently extracted data on pain control, survival, and SREs and evaluated the quality of each study. Meta-analyses were performed when there were two or more trials with similar outcomes.Twelve trials met our inclusion criteria and included 1,767 patients. Studies were placebo-controlled, or had compared bisphosphonates with other modalities (chemotherapy, radiation therapy, or radioisotope therapy), or had used different bisphosphonates as active controls. Randomized controlled trials did not report adequate descriptions of randomization procedures, allocation concealment, and blinding, resulting in low-quality scores. Patients treated with zoledronic acid + chemotherapy had fewer SREs than those receiving chemotherapy alone (relative risk (RR) 0.81, 95 % confidence interval (CI) 0.67-0.97). Pain control improved when a bisphosphonate was added to another treatment modality (chemotherapy or radiation; RR 1.18, 95 %CI 1.0-1.4). Bisphosphonate therapy improved survival compared to controls, but the difference failed to reach statistical significance (mean of 72 days, 95 %CI -8.9 to 152.9).Treatment with bisphosphonates reduced SREs, improved pain control, and showed a trend to increased survival. Bisphosphonates should be used in the treatment of patients with lung cancer and bone metastases.

SUBMITTER: Lopez-Olivo MA

PROVIDER: S-EPMC3691019 | biostudies-other | 2012 Nov

REPOSITORIES: biostudies-other

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Bisphosphonates in the treatment of patients with lung cancer and metastatic bone disease: a systematic review and meta-analysis.

Lopez-Olivo Maria A MA Shah Nimit A NA Pratt Greg G Risser Jan M JM Symanski Elaine E Suarez-Almazor Maria E ME

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 20120907 11

<h4>Purpose</h4>Bisphosphonates are known to prevent skeletal-related events (SREs) in advanced breast cancer, prostate cancer, and multiple myeloma. This systematic review assessed the efficacy of bisphosphonates in preventing SREs, controlling pain, and overall survival in patients with bone metastases from lung cancer.<h4>Methods</h4>We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Library databases through November 10, 2011 for controlled trials that included lung cancer patient ...[more]

PMID: 22956190

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Project description:OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment. METHODS: Literature databases were searched from inception to the 30th June 2012 for clinical trials of bisphosphonates to treat OA pain. Data was appraised and levels of evidence determined qualitatively using best evidence synthesis from the Cochrane Collaboration. The two largest studies were conducted with risedronate in the treatment of knee OA, for which meta-analyses were performed for pain and functional outcomes. RESULTS: Our searches found 13/297 eligible studies, which included a total of 3832 participants. The trials recruited participants with OA of the hand (n=1), knee (n=8), knee and spine (n=3), or hip (n=1). Our meta-analysis of the two largest knee studies using risedronate 15 mg showed odds ratios favouring placebo interventions for the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (1.73), WOMAC function (2.03), and WOMAC stiffness (1.82). However, 8 trials (61.5%) reported that bisphosphonates improve pain assessed by VAS scores and 2 (38.5%) reported significant improvement in WOMAC pain scores compared to control groups. CONCLUSIONS: There is limited evidence that bisphosphonates are effective in the treatment of OA pain. Limitations of the studies we analysed included the differences in duration of bisphosphonate use, the dose and route of administration and the lack of long-term data on OA joint structure modification post-bisphosphonate therapy. Future more targeted studies are required to appreciate the value of bisphosphonates in treating osteoarthritis pain. TRIAL REGISTRATION: PROSPERO Register CRD42012002541.

Project description:BackgroundBone mineral density (BMD) decreases postrenal transplantation. Evidence demonstrating the effects of bisphosphonates on BMD and fracture risk beyond 1-year posttransplant is sparse in existing literature, but remains essential to enhance clinical outcomes in this population.ObjectiveOur study aimed to systematically review and meta-analyze the current literature on the use of any bisphosphonate in the adult renal transplant population beyond the first year of renal transplant to determine its effect on BMD and fracture incidence.DesignWe conducted a systematic review and meta-analysis of primary research literature that included full-text, English-language, original randomized clinical trials (RCTs) and observational studies.SettingPatient data were primarily captured in an outpatient setting across various studies.PatientsOur population of interest was patients older than 18 years who received deceased/living donor kidney transplantation and any bisphosphonate with a follow-up greater than 12 months posttransplantation.MeasurementsThe primary outcome was change in BMD from baseline. Secondary outcomes were the incidence of fractures and effects of other confounders on bone health.MethodsWe included RCTs and observational studies that satisfied our inclusion criteria. Each study was analyzed for risk of bias and data were extrapolated to analyze for overall statistical significance accounting for heterogeneity of studies.ResultsSixteen studies (N = 1762) were analyzed. The follow-up ranged from 12 to 98 months. There was a nonsignificant improvement in BMD with bisphosphonate treatment persisting into the second and third years posttransplant at the lumbar spine. The calculated standardized mean BMD difference was -0.29 (-0.75 to 0.17), P = .22. Only 5 studies reported a total of 43 new fractures. Prednisone (P < .01), low body weight (P < .001), low body mass index (P < .01), and male gender (P < .05) correlated with reduced lumbar and femoral BMD.LimitationsLimitations of this review include the use of BMD as a surrogate outcome, the bias of the included studies, and the incomplete reporting data in numerous analyzed studies.ConclusionsWe demonstrate no statistically significant benefit of bisphosphonate treatment on BMD beyond the first year postrenal transplantation. Despite heterogeneity of treatment, a differential nonsignificant improvement in lumbar spine BMD was consistent and may be clinically relevant.Trial registrationPROSPERO CRD42019125593.

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Project description: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.

Dataset Information

Bisphosphonates in the treatment of patients with lung cancer and metastatic bone disease: a systematic review and meta-analysis.

Publications

Bisphosphonates in the treatment of patients with lung cancer and metastatic bone disease: a systematic review and meta-analysis.

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