Zoledronic acid is a high potency bisphosphonate that can be administered intravenously over a shorter period of time than pamidronate. Its efficacy in patients with osteolytic metastases (multiple myeloma or breast cancer) was evaluated in a phase II trial of 280 patients who were randomly assigned to receive pamidronate (90 mg IV over two hours) or one of three different doses of zoledronic acid (0.4, 2.0 or 4.0 mg, IV over five minutes).r Zoledronic acid at a dose of 2 or 4 mg but not 0.4 mg was at least as effective as pamidronate in reducing the need for radiation therapy for symptomatic progression of bone metastases; adverse events were similar in nature and frequency.
Similar results were obtained in a randomized, double-blind phase III trial in 1,648 patients with advanced multiple myeloma or breast cancer.r Patients were randomly assigned to receive one of two different doses of zoledronic acid (4 or 8 mg administered IV over 5 or 15 minutes) or pamidronate (90 mg IV over two hours); infusions were repeated every three to four weeks for 12 months. All participants received a daily 500 mg calcium supplement and 400 to 500 IU of vitamin D throughout the study. The following findings were noted: The proportion of patients with at least one skeletal event during the first 13 months of the study, and the median time to the first event (12 months) was similar in all three treatment groups. The proportion of patients who required therapeutic bone irradiation was significantly lower in the zoledronic acid 4 mg group compared to pamidronate both in the entire group (15 versus 20 percent), and in women receiving hormone therapy for breast cancer (16 versus 25 percent). Both agents were equally well tolerated, and the most common adverse events were bone pain, nausea, fatigue, and fever. Although 12 percent of patients receiving 4 mg of zoledronic acid over a five-minute period developed deterioration of previously normal renal function, an increase in the infusion volume to 100 mL, and lengthening the infusion time to 15 minutes reduced the incidence of renal dysfunction to the same levels as with pamidronate (8 and 9 percent, respectively). Long-term data (25 months of follow-up) showed equivalent renal effects (changes in creatinine) for zoledronic acid 4 mg over 15 minutes and pamidronate over two hours.r
Berenson et al (2006) reported that in a subset of myeloma patients (those with elevated bone-specific alkaline phosphatase (BALP) at diagnosis), zoledronic acid may increase survival. The study was a retrospective review of patients with myeloma and bone lesions being treated with zoledronic acid or pamidronate. Whilst for the overall patient population (n = 353) survival was comparable between the 2 groups, for a subset of patients with an elevated BALP at diagnosis, survival was significantly increased (82% vs 53%) in those treated with zoledronic acid. The authors suggested that prospective studies are required to investigate this finding.r
In light of available data showing a 9.5-fold greater risk of osteonecrosis of the jaw with zoledronic acid compared with pamidronate, patients may prefer the latter agent until more data become available on this issue.r