Zoledronic acid delays the onset of skeletal‐related events and progression of skeletal disease in patients with advanced renal cell carcinoma

Abstract

BACKGROUND The objective of this study was to assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to renal cell carcinoma (RCC). METHODS A retrospective subset analysis of patients with RCC enrolled in a multicenter, randomized, placebo‐controlled study of zoledronic acid was performed. Patients were randomized to receive zoledronic acid (4 or 8 mg as a 15‐minute infusion) or placebo with concomitant antineoplastic therapy every 3 weeks for 9 months. The primary efficacy analysis was the proportion of patients with one or more skeletal‐related events (SREs), which were defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate (events per year), disease progression, and multiple event analysis. RESULTS In this subset of 74 patients with RCC, zoledronic acid (4 mg) was found to significantly reduce the proportion of patients with an SRE (37% vs. 74% for placebo; P = 0.015). Similarly, zoledronic acid significantly reduced the mean skeletal morbidity rate (2.68 vs. 3.38 for placebo; P = 0.014) and extended the time to the first event (median not reached vs. 72 days for placebo; P = 0.006). A multiple event analysis demonstrated that the risk of developing an SRE was reduced by 61% compared with placebo (hazard ratio of 0.394; P = 0.008). The median time to progression of bone lesions was significantly longer for patients who were treated with zoledronic acid (P = 0.014 vs. placebo). Zoledronic acid appeared to be well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and emesis. CONCLUSIONS Zoledronic acid (4 mg as a 15‐minute infusion) demonstrated significant clinical benefit in patients with bone metastases from RCC, suggesting that further investigation of zoledronic acid in this patient population is warranted. Cancer 2003;98:962–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11571

Bone metastases affect prognosis but not effectiveness of third-line targeted therapies in patients with metastatic renal cell carcinoma

“…In their subgroup analysis of 74 patients with mRCC, Lipton and colleagues found that zoledronic acid extended the time to the first event and reduced the risk of SRE by 61% compared to placebo (HR 0.394, p = 0.008). 19 In a recent retrospective analysis on 76 patients affected by mRCC and all treated with sunitinib, 35 received bisphosphonate and 41 were non-users. In the treated group, the bisphosphonate decreased the risk of progression by 45% (HR 0.55, p < 0.001) and of the risk of death by 60% (HR 0.4, p = 0.029).…”

Kidney Cancer

“…Surgery also may be appropriate for selected patients with malignant spinal cord compression, or impending or actual fractures in weight-bearing bones, if the rest of the disease burden is limited. Furthermore, radiation therapy along with bisphosphonates 82,83 is considered for palliation, particularly of painful bone metastases. The frequency of clinic visits or radiographic and laboratory assessments depends on the individual needs of the patient.…”

Safety of Intravenous and Oral Bisphosphonates and Compliance With Dosing Regimens

“…Zoledronic acid has the shortest approved infusion time of any bisphosphonate (15 minutes), compared with the 1-4 hours required for pamidronate and ibandronate. In addition, zoledronic acid (4 mg) is unique among other bisphosphonates because it effectively reduces the incidence and delays the onset of skeletal complications in patients with osteolytic, mixed, and osteoblastic bone lesions from a wide range of primary malignancies, including multiple myeloma, breast, prostate, and lung cancer, as well as a variety of other solid tumors [11][12][13][14][15].…”