Renal safety of zoledronic acid in patients with bone metastases from breast cancer (BC) or other tumors treated with IV BisphosphonateS (BPS) for up to ten years

Background: BPS prevent or reduce the incidence of skeletal complications in patients (pts) with bone metastases. However there are few data on the renal safety of IV BPS beyond 2 yrs of administration. Materials and Methods: We retrospectively analyzed serum creatinine (SCr) levels in pts receiving IV BPS for > 24 months (mos). All pts received zoledronic acid (Zometa) 4 mg every 3-4 wks, but the duration of pamidronate (Aredia) 90 mg every 3-4 wks was also included in data analyses. Pre- and post-treatment SCr levels, and the highest levels attained were recorded. A notable SCr increase was defined as: an increase of 0.5 mg/dL for pts with baseline SCr 1.4 mg/dL; 1.0 mg/dL increase for pts with baseline SCr >1.4 mg/dL; or 2x increase over baseline. Concomitant cytotoxic treatments were also reported. Results: 51 pts with bone metastases were analysed. Characteristics: 42 BC, 7 multiple myeloma (MM), one renal cell carcinoma (RCC), and one prostate cancer; median age at treatment start: 57 yrs (range: 30-81). All pts received zoledronic acid; 43 started with pamidronate then switched to zoledronic acid. Median overall duration of BPS administration: 29 mos (24+ to 124+); zoledronic acid, 21 mos (2+ to 40+). Twenty-four out of 42 BC pts received different chemotherapy regimens, median number of chemotherapy lines was 2 (range: 1-5). Other additional risks of nephrotoxicity were: underlying disease (MM, prostate cancer), prior nephrectomy (RCC), or advanced age (25% of pts > 70 yrs). Median SCr levels: baseline, 0.82 mg/dL (range, 0.4-1.3); time of analysis, 0.89 mg/dL (0.4-2); highest level, 1.01 mg/dL (0.5-2). Safety: notable SCr increases, 4 pts (7.8%; all CTC grade 1). As of this date, 44 pts still receive zoledronic acid. Four pts stopped the treatment (1 pt for SCr = 2 mg/dL; 2 pts with stable limited bone disease for physician decision; 1 pt for jaw osteonecrosis), and 3 died for progressive disease. Conclusions: These data demonstrate that IV BPS, including zoledronic acid, are safe during prolonged treatment administration (up to 10 years). Renal function is maintained in pts receiving multiple cytotoxic therapies and with additional risks of nephrotoxicity.