Oral adjuvant clodronate therapy could improve overall survival in early breast cancer: results from an updated systematic review and meta-analysis.

Object: The aim of this study was to evaluate the effectiveness of clodronate in the adjuvant therapy of early breast cancer on patient survival.

Methods: We performed a literature search to identify studies that investigated the effects of clodronate treatment on early breast cancer. Random and fixed-effect meta-analytical models were used where indicated and between-study heterogeneity was assessed. The primary study end-points were overall survival. Secondary end-points were bone metastasis-free survival and non-skeletal metastasis (mainly visceral metastases) free survival.

Results: Four randomised controlled trials met the inclusion criteria. Risk ratio (95% confidence interval (CI)) of overall survival was 0.84 (0.56-1.26); risk ratio (95% CI) of bone metastasis-free survival was 0.77 (0.58-1.02); risk ratio (95% CI) of non-bone metastasis-free survival was 0.89 (0.61-1.30). Outcomes after sensitivity analysis were: risk ratio (95% CI) of overall survival was 0.71 (0.52-0.96); risk ratio (95% CI) of bone metastasis-free survival was 0.70 (0.56-0.86); risk ratio (95% CI) of non-bone metastasis-free survival was 0.76 (0.64-0.92).

Conclusion: Compared with the control arm, adjuvant treatment with clodronate may improve the overall survival, bone metastasis-free survival and non-bone metastasis-free (mainly visceral metastases) survival in patients with early breast cancer. However, further meta-analyses involving all known randomised trials with analysis of sub-groups by age or menopausal status, accessing original trial data, should be performed.