Safety of zoledronic acid in patients who have previously received bisphosphonate therapy

Abstract

8156 Background: Because pamidronate was the previous standard of care for patients with bone involvement from breast cancer, many patients will be treated with zoledronic acid after exposure to pamidronate. Therefore, it is important to demonstrate that switching patients from pamidronate to zoledronic acid will not result in an increase in bisphosphonate-related side effects. A phase IV study was conducted to examine the benefits of zoledronic acid on pain palliation and quality of life and to assess the overall and renal safety profile of zoledronic acid in patients with breast cancer, prostate cancer, and multiple myeloma with or without a history of bisphosphonate therapy. Methods: Zoledronic acid (4 mg) was administered via 15-minute infusion every 3 or 4 weeks for 6 infusions. Adverse events were recorded, and serum creatinine was measured before each infusion. Notable serum creatinine increases were defined as ≥ 0.5 mg/dL, if baseline was < 1.4 mg/dL; ≥ 1 mg/dL, if baseline was ≥ 1.4 mg/dL; or as any doubling of serum creatinine. Adverse events and serum creatinine levels were reported by tumor type and history of bisphosphonate therapy. Results: Among 638 patients, 415 (65%) had received prior bisphosphonate therapy, primarily pamidronate (95.4%). Among 461 patients with pain at baseline, mean pain scores decreased significantly (P < .01) at every postbaseline assessment. The most frequent adverse events in all patient groups were fatigue, nausea, and arthralgia. Notable serum creatinine increases occurred in 6.3% of patients and were somewhat more common in patients with a history of bisphosphonate therapy (7.7%) versus bisphosphonate-naive patients (4.5%). Treatment delays from serum creatinine increase occurred in 1.5% of patients with prior bisphosphonate exposure and 0.5% of bisphosphonate-naive patients. However, elevations in serum creatinine and treatment delays did not correlate with duration of prior bisphosphonate therapy or tumor type. Conclusions: Zoledronic acid (4 mg via 15-minute infusion) is safe and well tolerated in patients who have received prior bisphosphonate therapy, regardless of therapy duration. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals