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

Department of Medicine, Milton S. Hershey Medical Center, PO Box 850 H-46, Hershey, PA 17033, USA.
Cancer (Impact Factor: 5.2). 10/2003; 98(5):962-9. DOI: 10.1002/cncr.11571
Source: PubMed

ABSTRACT 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).
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.
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.
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.

  • European Urology 04/2014; · 10.48 Impact Factor
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    ABSTRACT: Bone metastases (BMs) are frequently present in patients with metastatic renal cell carcinoma (mRCC) and cause significant morbidity. The purpose of this analysis was to assess the impact of BMs and bisphosphonate therapy (BT) on outcomes in mRCC. We conducted a pooled analysis of patients with mRCC treated from 2003 to 2011 in phase 2 and 3 trials. Statistical analyses were performed using Cox regression and the Kaplan-Meier method. We identified 2749 patients treated with sunitinib (n=1059), sorafenib (n=355), axitinib (n=359), temsirolimus (n=208), temsirolimus plus interferon-α (IFN-α) (n=208), or IFN-α (n=560), with 28% (n=781) having BMs. A total of 285 patients (10.4%) received BT. The presence of BMs in patients was associated with shorter overall survival (OS) when compared with patients without BMs (13.2 vs 20.2 mo, respectively; p<0.0001) and shorter progression-free survival (PFS) (5.1 vs 6.7 mo, respectively; p<0.0008). When stratified by risk groups, the presence of BMs was associated with shorter OS in all risk groups. The use of BT in patients with BMs was not associated with improved OS compared with patients who did not receive BT (13.3 vs 13.1 mo, respectively; p=0.3801) or improved PFS (5.1 vs 4.9 mo, respectively; p=0.1785). Bisphosphonate users with BMs did not have a decreased rate of skeletal-related events (SREs) compared with nonusers (8.6% vs 5.8%, respectively; p=0.191). In addition, BT was associated with increased rates of hypocalcemia, renal insufficiency, and osteonecrosis of the jaw (p<0.0001). Data were analyzed retrospectively. We confirm that the presence of BMs is associated with shorter survival in mRCC. BT did not affect survival or SRE prevention and was associated with increased toxicity. In this analysis, we demonstrate that bone metastases are associated with shorter survival in patients with metastatic renal cell carcinoma. In addition, we call into question the utility of bisphosphonate therapy in this population.
    European Urology 02/2014; · 10.48 Impact Factor
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    Annals of Oncology 09/2014; 25 Suppl 3:iii49-iii56. · 7.38 Impact Factor


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