Intravenous
bisphosphonates are the preferred treatment to prevent skeletal complications for patients with
breast cancer and bone
metastases.
Pamidronate, a single-
nitrogen bisphosphonate, was the early standard of care for such patients based on 2 large, placebo-controlled trials involving 754 patients.
Zoledronic acid, a new-generation
bisphosphonate containing 2 nitrogens, was evaluated
in 1130 patients with
breast cancer in a large, randomized, comparative, phase III trial with
pamidronate. At 25 months,
zoledronic acid (4 mg) significantly reduced the overall risk of developing a skeletal-related event (SRE) by an additional 20% versus 90 mg
pamidronate by multiple-event analysis. Furthermore,
zoledronic acid was at least as effective as
pamidronate in reducing the proportion of patients with > or = 1 SRE and in delaying the onset of SREs. Moreover, a retrospective subset analysis of 352 patients with > or = 1 osteolytic lesion proved
zoledronic acid more effective than
pamidronate in reducing the risk and delaying the onset of SREs. Intravenous
ibandronate (6 mg via 1-2-hour infusion) was evaluated in a placebo-controlled, phase III trial of 466 patients and was significantly more effective than placebo in reducing the number of 12-week treatment periods in which an SRE occurred. The safety profiles among all intravenous
bisphosphonates were similar; patients treated with intravenous
bisphosphonates reported notably less bone
pain but a higher incidence of mild to moderate transient infusion-related adverse events (eg,
nausea,
vomiting,
myalgia, and
anorexia) compared with placebo. In summary, intravenous
bisphosphonates are effective for the treatment of bone
metastases in patients with
breast cancer and have similar safety profiles, but the shorter infusion time and greater efficacy of
zoledronic acid in reducing overall skeletal morbidity provide advantages over other available agents.