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

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.