Renal safety of zoledronic acid in patients with breast cancer

Bisphosphonates provide a supportive benefit to many patients with bone metastases. The renal safety of zoledronic acid in patients with breast cancer was compared with that of pamidronate in a number of trials and it has been found that zoledronic acid (4 mg via 15-minute infusion) has a renal safety profile comparable to that of pamidronate (90 mg via 2-hour infusion). No patient with breast cancer treated with 4 mg zoledronic acid via 15-minute infusion experienced grade 3 or 4 serum creatinine elevation according to the National Cancer Institute Common Toxicity Criteria.

The American Society of Clinical Oncology (ASCO) updated the guidelines on the role of bisphosphonates in women with breast cancer and addressed the subject of bone health in these women.¹ The use of intravenous zoledronic acid 4 mg over 15 minutes or pamidronate 90 mg delivered over 2 hours every 3 to 4 weeks is recommended for patients with plain radiographic evidence of bone destruction. It is also reasonable to initiate IV bisphosphonate therapy in patients with bone destruction through imaging, but who have normal plain radiographs. The presence or absence of bone pain should not be a factor in initiating bisphosphonates.¹ At present, zoledronic acid (Zometa) is listed on the PBS for the treatment of patients with multiple myeloma, bone metastases from breast cancer, bone metastases from hormone-resistant prostate cancer and hypercalcaemia of malignancy refractory to anti-neoplastic therapy.Repeated dose studies in cancer patients with bone metastases suggest that the 15 minute infusion of zoledronic acid provides the same efficacy with an even greater safety margin. Accordingly, a 15 minute infusion rate of zoledronic acid 4 mg was chosen as the recommended schedule.² Patients must be assessed prior to administration to ensure adequate hydration. They should also receive oral calcium supplement of 500mg daily and multi-vitamin containing 400 IU of vitamin D daily.Once initiated, IV bisphosphonates should be continued as long as tolerated or until evidence of substantial decline in performance status. According to the product information, patients who receive zoledronic acid should have serum creatinine assessed prior to each dose.² No changes in dose, infusion duration or interval is necessary for patients with pre-existing renal disease if serum creatinine is < 3.0 mg/dL (265 umol/L). Patients being treated for bone metastases should have the dose of zoledronic acid withheld if renal function has deteriorated and resumed only when the creatinine level returned to within 10% of the baseline value. Zoledronic acid is not recommended in patients with severe renal impairment (creatinine levels > 400 micromol/L for patients with tumour-induced hypercalcaemia and > 265 micromol/L for patients with bone metastases).A randomized, double-blind, multicentre, comparative trial performed by Rosen LS et al. compared the long-term (25-month) safety and efficacy of zoledronic acid with pamidronate by randomizing patients to zoledronic acid (4 or 8 mg) versus pamidronate (90 mg) every 3 to 4 weeks for up to 24 months. The results demonstrated a significant reduction in the risk of skeletal-related events with the use of zoledronic acid (4mg) by an additional 20% (P = 0.025) compared with pamidronate. There were no significant differences in renal safety profiles between the 4 mg zoledronic acid group and the 90 mg pamidronate group during long-term treatment.³Lipton A et al. presented at the 4th European Breast Cancer Conference that time to first notable serum creatinine increase was similar in the zoledronic acid and pamidronate groups. The percentage of breast cancer patients with notable serum creatinine increase was also similar in the zoledronic acid and pamidronate groups. No NCI Grade 3 or 4 serum creatinine increases occurred in breast cancer patients treated with zoledronic acid. The findings from all the above mentioned studies thus support that zoledronic acid (4 mg via 15-minute infusion) has a renal safety profile comparable to that of pamidronate (90 mg via 2-hour infusion) in patients with breast cancer. References:1. Hillner B, et al. J Clin Oncol. 2003; 21: 4042-4057.2. Zometa product information3. Rosen LS, Gordon D, Kaminski M et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma. Cancer. 2003; 98: 1735-1744.4. Lipton A, et al. Presented at: 4th European Breast Cancer Conference. 2004: Poster 296.Please click here to view the full article.