Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases: A double-blind, randomized dose-response study

James R. Berenson, Lee S. Rosen, Anthony Howell, Lester Porter, Robert E. Coleman, Walter Morley, Robert Dreicer, Steven A. Kuross, Allan Lipton, John J. Seaman

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453 Scopus citations

Abstract

BACKGROUND. This study evaluated the dose-response relation for zoledronic acid, a new generation high potency bisphosphonate, given as a 5-minute infusion in patients with malignant osteolytic disease. METHODS. Two-hundred eighty patients with osteolytic lesions due to metastatic breast carcinoma or multiple myeloma were randomized to double-blind treatment with either 0.4, 2.0, or 4.0 mg of zoledronic acid or 90 mg pamidronate. The primary efficacy endpoint was the proportion of patients receiving radiation to bone. Other skeletal-related events, bone mineral density (BMD), bone markers, Eastern Cooperative Oncology Group performance status, pain and analgesic scores, and safety also were evaluated. RESULTS. Zoledronic acid at doses of 2.0 and 4.0 mg and pamidronate at a dose of 90 mg each significantly reduced the need for radiation therapy to bone (P < 0.05) in contrast with 0.4 mg zoledronic acid, which did not. Skeletal-related events of any kind, pathologic fractures, and hypercalcemia also occurred less frequently in patients treated with 2.0 or 4.0 mg zoledronic acid or pamidronate than with 0.4 mg zoledronic acid. Increases in lumbar spine BMD (6.2-9.6%) and decreases in the bone resorption marker N-telopeptide (range, -37.1 to -60.8%) were observed for all treatment groups. Skeletal pain, fatigue, nausea, vomiting, and headache were the most commonly reported adverse events. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate. CONCLUSIONS. A 5-minute infusion of 2.0-4.0 mg zoledronic acid was at least as effective as a 2-hour 90-mg pamidronate infusion in treatment of osteolytic metastases. A 0.4-mg dose of zoledronic acid was significantly less effective. Both zoledronic acid and pamidronate were well tolerated.

Original languageEnglish (US)
Pages (from-to)1191-1200
Number of pages10
JournalCancer
Volume91
Issue number7
DOIs
StatePublished - Apr 1 2001

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Berenson, J. R., Rosen, L. S., Howell, A., Porter, L., Coleman, R. E., Morley, W., Dreicer, R., Kuross, S. A., Lipton, A., & Seaman, J. J. (2001). Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases: A double-blind, randomized dose-response study. Cancer, 91(7), 1191-1200. https://doi.org/10.1002/1097-0142(20010401)91:7<1191::AID-CNCR1119>3.0.CO;2-0