Zoledronic Acid Significantly Reduces Skeletal Complications Compared With Placebo in Japanese Women With Bone Metastases From Breast Cancer: A Randomized, Placebo-Controlled Trial

2005 ◽  
Vol 23 (15) ◽  
pp. 3314-3321 ◽  
Author(s):  
Norio Kohno ◽  
Kenjiro Aogi ◽  
Hironobu Minami ◽  
Seigo Nakamura ◽  
Taro Asaga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Rate Ratio ◽  
Cox Regression ◽  
Permutation Test ◽  
Japanese Women ◽  
Event Analysis ◽  
End Points ◽  
Skeletal Complications

Purpose To investigate the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer. Patients and Methods Women with bone metastases (N = 228) were randomly assigned to receive 4 mg zoledronic acid (n = 114) or placebo (n = 114) via 15-minute infusions every 4 weeks for 1 year. The primary efficacy end point was the skeletal-related event (SRE) rate ratio between treatment groups. An SRE was defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. Secondary end points included percentage of patients with at least one SRE, time-to-first SRE, and Andersen-Gill multiple-event analysis. Results The SRE rate ratio at 1 year (excluding HCM and adjusted for prior fracture) was 0.61 (permutation test; P = .027), indicating that zoledronic acid reduced the rate of SRE by 39% compared with placebo. The percentage of patients with at least one SRE (excluding HCM) was significantly reduced by 20% by zoledronic acid (29.8% v 49.6% for placebo; P = .003). Zoledronic acid significantly delayed time-to-first SRE (median not reached v 364 days; Cox regression; P = .007) and reduced the risk of SREs by 41% in multiple event analysis (risk ratio = 0.59; P = .019) compared with placebo. Zoledronic acid was well tolerated with a safety profile similar to placebo. No patient treated with zoledronic acid had grade 3 or 4 serum creatinine increase. Conclusion Zoledronic acid significantly reduced skeletal complications compared with placebo across multiple end points in Japanese women with bone metastases from breast cancer.

Renal safety of zoledronic acid administration beyond 24 months in breast cancer patients with bone metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19669-19669
Author(s):  
M. K. Altundag ◽  
M. Dincer ◽  
H. Harputluoglu ◽  
S. Aksoy ◽  
Y. Ozisik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Skeletal Complications ◽  
Few Data ◽  
Acid Administration ◽  
Renal Safety

19669 Background: Zoledronic acid (ZA) delays the onset or reduces the incidence of skeletal complications in breast cancer patients with bone metastases. However there are few data on the long-term renal safety of ZA. Methods: We retrospectively evaluated 43 breast cancer patients with bone metastases who received ZA more than 24 months. The following parameters measured prior to first ZA use and after the last dose of ZA administration were compared: serum creatinine (SCr), blood urea nitrogen (BUN), alkaline phosphatase (ALP), calcium (Ca), and phosphorous (P). Results: Forty-three breast cancer patients with documented bone metastases were evaluated. Median age at the start of treatment was 53 years (range, 37 to 77). Median overall duration of ZA administration was 36 months (25 to 62). There were no statistically significant differences in the pre- and post-treatment levels of SCr, BUN, Ca and P. However, ALP levels after long-term ZA administration were decreased significantly (P <0.05). Conclusion: More than 24 months of ZA administration did not adversely affect the renal function. ZA can be used safely in breast cancer patients with bone metastases beyond 2 years. [Table: see text] No significant financial relationships to disclose.

Efficacy of zoledronic acid versus placebo on biochemical markers of bone metabolism in patients with breast cancer metastatic to bone

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10559-10559
Author(s):  
N. Kohno ◽  
K. Aogi ◽  
H. Minami ◽  
S. Takashima
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Bone Metabolism ◽  
Biochemical Markers ◽  
Breast Cancer Patients ◽  
Clinical Complications ◽  
Study Results ◽  
Skeletal Complications ◽  
Sensitive Marker

10559 Background: Zoledronic acid reduces the levels of bone markers and the risk of skeletal complications in patients with bone metastases. Recently, a correlation between the levels of biochemical markers of bone metabolism and the risk of clinical complications (ie, skeletal complications, disease progression, and death) in patients with bone metastases has been reported. The effect of zoledronic acid on bone marker levels was assessed in patients with bone metastases from breast cancer in a multicenter randomized trial conducted in Japan. Methods: Women with bone metastases secondary to breast cancer (N = 228) were randomized to 4 mg zoledronic acid (n = 114) or placebo (n = 114) every 4 weeks for 1 year. Levels of urinary N-telopeptide (NTX), a sensitive marker of bone resorption, were measured at baseline and regularly throughout the study. Results: The table shows that zoledronic acid reduced NTX levels in patients compared with placebo. Patients treated with zoledronic acid had a mean decrease of 61% from baseline NTX levels at week 2. This decrease was maintained throughout the study in this treatment group and was 54% at week 52. In contrast, patients in the placebo group had a mean increase of 27% from baseline NTX levels at week 2, and levels of NTX continued to increase during the study, reaching 146% above baseline at week 52. Conclusions: This analysis shows that treatment with zoledronic acid reduced NTX levels in patients with bone metastases from breast cancer compared with placebo. These results are consistent with published reports in patients with prostate or lung cancer and are consistent with the significant reduction in skeletal morbidity observed in this trial in breast cancer patients. Zoledronic acid demonstrated a 39% reduction in skeletal morbidity in this patient population. [Table: see text] No significant financial relationships to disclose.

Benefits of zoledronic acid compared with placebo in breast cancer patients with bone metastases based on analysis of pain, analgesic use, and performance status

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10653-10653
Author(s):  
K. Aogi ◽  
N. Kohno ◽  
H. Minami ◽  
S. Takashima
Keyword(s):  
Breast Cancer ◽  
Placebo Group ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Performance Status ◽  
Acid Group ◽  
Breast Cancer Patients ◽  
Skeletal Complications ◽  
Ecog Ps ◽  
Analgesic Use

10653 Background: We previously reported that zoledronic acid significantly reduced skeletal complications by 39% compared with placebo in breast cancer (BC) patients with bone metastases in a multicenter randomized trial conducted in Japan. To assess the effect of zoledronic acid in the maintenance of patient’s mobility or autonomy, we conducted a retrospective analysis of pain, analgesic use, and performance status (PS) among patients of this trial. Methods: 228 women with bone metastases were randomized to 4 mg zoledronic acid (n = 114) or placebo (n = 114) every 4 weeks for 1 year. At baseline and every 4 weeks during treatment, pain scores were assessed using the Brief Pain Inventory (BPI) on a scale of 0 to 10, and analgesic use was scored on a 4-point scale from none (0) to strong narcotics such as morphine (4). Eastern Cooperative Oncology Group (ECOG) PS was assessed at baseline and at study end. Results: Unlike patients receiving placebo who’s pain scores increased, patients treated with zoledronic acid had a significant decrease from baseline BPI composite pain score from week 4 to week 52: mean decrease of 0.86 in the zoledronic acid group at week 52 versus a mean increase of 0.62 in the placebo group; P < .05. Patients treated with zoledronic acid had very little change in analgesic scores, whereas patients in the placebo group had a mean increase in analgesic score (approximately 0.5) by study end. Shift table analysis of ECOG PS showed that 61% of patients in the zoledronic acid group had no change in PS, and 28% had worsening of ECOG PS of at least 1 grade from baseline to study end. In comparison, 54% of patients in the placebo group had no change in PS, and 36% had worsening of PS. Approximately 10% of patients in both treatment groups had an improvement in PS. Conclusions: This analysis shows that treatment with zoledronic acid reduced pain and prevented a worsening of ECOG PS in a larger percentage of patients compared with placebo, consistent with the demonstrated reduction in the rate of skeletal complications. This suggests that zoledronic acid may improve quality of life and maintain autonomy and mobility in breast cancer patients with bone metastases. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document