Efficacy and safety of intravenous bisphosphonates beyond two years

Background: Metastatic bone disease, a common complication of malignancy, causes significant morbidity in affected patients. Intravenous bisphosphonates (IBPs) have shown efficacy in preventing skeletal morbidity, however few studies have investigated their efficacy and safety in cancer patients beyond 2 years of use. This retrospective study documents long term clinical use of IBPs among a variety of patient populations and clinical settings. Methods: This study is a multi-center retrospective chart review of patients who received IBPs (Pamidronate or Zoledronic Acid) for more than 24 months. Patients were at least 18 years of age and had tumor-associated bone disease. Data analysis focused on skeletal related events (SREs) and drug related toxicities such as renal failure and osteonecrosis of the jaw (ONJ). Results: Ninety-two patients were included with the most common diagnosis being multiple myeloma. A total of 44 SREs occurred among 23 patients. Mean time to first SRE was 515 days. The rate of skeletal events in the first 2 years of treatment was 0.70, while skeletal morbidity rate (SMR) in subsequent years was 0.16. Thirteen patients experienced renal toxicity; most patients’ renal function normalized after brief or permanent cessation of IBP therapy. ONJ was associated with 5 patients. Conclusion: Continuation of IBP therapy for skeletal metastasis after 2 years of treatment may improve skeletal morbidity. Similar to the first 2 years of treatment, significant toxicities such as renal failure and ONJ are uncommon.