Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration

Abstract

Patients with bone metastases from breast cancer often experience substantial skeletal complications -- including debilitating bone pain -- which negatively affect quality of life. Zoledronic acid (4 mg) has been demonstrated to reduce significantly the risk of skeletal complications in these patients and is administered via a short, 15-min infusion every 3 weeks, allowing the possibility for home administration. This study compared the efficacy and safety of zoledronic acid administered in the community setting vs the hospital setting in breast cancer patients with > or =1 bone metastasis receiving hormonal therapy. After a lead-in phase of three infusions of 4 mg zoledronic acid in the hospital setting, 101 patients were randomized to receive three open-label infusions in the community or hospital setting, followed by three infusions in the opposite venue (a total of nine infusions). The Brief Pain Inventory (BPI) and the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) were used to assess potential benefits of zoledronic acid therapy. At study end, analysis of the BPI showed significant reductions in worst pain (P=0.008) and average pain in the last 7 days (P=0.039), and interference with general activity (P=0.012). In each case, there were significantly greater improvements in pain scores after treatment in the community setting compared with the hospital crossover setting for worst pain (P=0.021), average pain (P=0.003), and interference with general activity (P=0.001). Overall global health status showed a significant median improvement of 8.3% (P=0.013) at study end. Physical, emotional, and social functioning also showed significant overall improvement (P=0.013, 0.005, and 0.043, respectively). Furthermore, physical, role, and social functioning showed significantly greater improvements after treatment in the community setting compared with the hospital crossover setting (P=0.018, 0.001, and 0.026, respectively). There was no difference between hospital and community administration in renal or other toxicity, with zoledronic acid being well tolerated in both treatment settings. These data confirm the safety and quality-of-life benefits of zoledronic acid in breast cancer patients with bone metastases, particularly when administered in the community setting.

Figure 1

Study design. Zoledronic acid (4 mg) was administered intravenously via 15-min infusion every 3–4 weeks for a maximum of nine infusions. The study was divided into a hospital lead-in phase with three infusions and two community vs hospital crossover phases with three infusions in each setting for a total of nine infusions.

Figure 2

Mean serum creatinine values remained stable throughout treatment with zoledronic acid. Serum creatinine values were measured at baseline (BL), after each cycle, and at follow-up. Measurements during home administration were performed using an i-STAT handheld analyser (Abbott Diagnostics).

Figure 3

Zoledronic acid significantly improved Brief Pain Inventory (BPI) pain scores. Brief Pain Inventory was assessed at baseline, at the end of each cycle, and at final visit. Graph depicts mean change from baseline BPI scores reported during the hospital crossover phase, community crossover phase, and overall (score reported at final visit after nine infusions). ^*P<0.05; †P<0.005 compared with baseline values.

Figure 4

Zoledronic acid significantly improved EORTC QLQ-C30 quality-of-life scores. Graph depicts overall mean change from baseline quality-of-life scores reported at final visit after nine infusions. ^*P<0.05 compared with baseline values. EORTC QLQ-C30=European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30.

Figure 5

Zoledronic acid achieved significantly greater improvement in EORTC QLQ-C30 quality-of-life scores when administered in the community crossover phase compared with the hospital crossover phase. The EORTC QLQ-C30 questionnaire was assessed at baseline, at the end of each treatment phase (hospital lead-in, community crossover, and hospital crossover), and at final visit. Graph depicts mean change from baseline quality-of-life scores reported during the hospital crossover phase and the community crossover phase. ^*P<0.05; †P<0.001 compared with hospital lead-in score. EORTC QLQ-C30=European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30.