Beta-blocker use had no evident effect on CR. The beneficial effect of beta-blockers on DFS and OS in the epidemiological or perioperative setting remains variable, tumour-specific, and of low-level evidence at present.
Purpose
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.
Methods
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, SREs and evaluated the quality of each study. Meta-analyses were performed when there were two or more trials with similar outcomes.
Results
Twelve trials, met our inclusion criteria, and included 1,767 patients. Studies were placebo-controlled or compared bisphosphonates with other modalities (chemotherapy, radiation therapy, or radioisotope therapy), or 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 −8.9-152.9).
Conclusions
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.
Background
We conducted a systematic review of the literature to determine the efficacy and safety of denosumab in reducing skeletal-related events (SRE) in patients with bone metastases.
Methods
A literature search using MEDLINE, EMBASE, Web of Science and The Cochrane Collaboration Library identified relevant controlled clinical trials up-to-March 14, 2012. Two independent reviewers assessed studies for inclusion, according to predetermined criteria, and extracted relevant data. The primary outcomes of interest were SRE, time to first on-study SRE, and overall survival. Secondary outcomes included pain, quality of life, bone turnover markers (BTM), and adverse events.
Results
Six controlled trials including 6,142 patients were analyzed. Compared to zoledronic acid, denosumab had lower incidence of SRE with a risk ratio (RR) of 0.84 (95% confidence intervals (CI) 0.80-0.88), delayed the onset of first on-study SRE (RR 0.83; 95%CI 0.75-0.90) and time to worsening of pain (RR 0.84; 95%CI 0.77-0.91). No difference was observed in overall survival with pooled hazard ratio of 0.98 (95%CI 0.90-1.0). For total adverse events, denosumab was similar to zoledronic acid (RR 0.97; 95%CI 0.89-1.0). No significant differences were observed in the frequency of osteonecrosis of the jaw (RR 1.4; 95%CI 0.92-2.1). Patients on denosumab had a greater risk of developing hypocalcemia (RR 1.9; 95%CI 1.6-2.3).
Conclusions
Denosumab was more effective than zoledronic acid in reducing the incidence of SRE, and delayed the time to SRE. No differences were found between denosumab and zoledronic acid in reducing overall mortality, or in the frequency of overall adverse events.
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