Fax: (310) 423-1977
A Phase I, open label, dose ranging trial of intravenous bolus zoledronic acid, a novel bisphosphonate, in cancer patients with metastatic bone disease
Article first published online: 4 JAN 2001
Copyright © 2001 American Cancer Society
Volume 91, Issue 1, pages 144–154, 1 January 2001
How to Cite
Berenson, J. R., Vescio, R., Henick, K., Nishikubo, C., Rettig, M., Swift, R. A., Conde, F. and Von Teichert, J. M. (2001), A Phase I, open label, dose ranging trial of intravenous bolus zoledronic acid, a novel bisphosphonate, in cancer patients with metastatic bone disease. Cancer, 91: 144–154. doi: 10.1002/1097-0142(20010101)91:1<144::AID-CNCR19>3.0.CO;2-Q
- Issue published online: 4 JAN 2001
- Article first published online: 4 JAN 2001
- Manuscript Revised: 29 AUG 2000
- Manuscript Accepted: 29 AUG 2000
- Manuscript Received: 27 APR 2000
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
- bone metastasis;
- bone resorption;
- osteolytic lesion;
- zoledronic acid
Bone metastases typically are associated with osteolytic bone destruction, resulting in bone pain, pathologic fractures, spinal cord compression, and hypercalcemia. Bisphosphonates are potent inhibitors of normal and pathologic bone resorption and represent a significant therapeutic improvement in the management of patients with lytic bone metastases. Zoledronic acid is a new-generation, highly potent, nitrogen-containing bisphosphonate that to the authors knowledge is the most potent inhibitor of bone resorption currently in clinical trials. The objectives of the current study were to assess the safety and tolerability of increasing doses of zoledronic acid and to determine its activity with respect to reducing biochemical markers of bone resorption in cancer patients with bone metastases.
Forty-four cancer patients with bone metastases or primary bone lesions were enrolled sequentially into 1 of 5 fixed ascending-dose treatment groups. Each patient received a single intravenous bolus injection of 1, 2, 4, 8, or 16 mg of zoledronic acid over 30–60 seconds. Patients were monitored for 8 weeks for the evaluation of clinical findings, adverse events, vital signs, electrocardiograms, markers of bone resorption, and urinary N-acetyl-β-D-glucosaminidase.
Zoledronic acid was safe and well tolerated at all dose levels tested. Commonly reported adverse events included bone pain, fever, anorexia, constipation, and nausea, which were experienced by a similar proportion of patients in each treatment group. Seven patients reported serious adverse events, none of which appeared to be related to the study drug. Zoledronic acid effectively suppressed biochemical markers of bone resorption, including the highly specific markers N-telopeptide and deoxypyridinoline, for up to 8 weeks in the 2–16-mg dose groups and for a shorter duration in the 1-mg group.
In the current study, zoledronic acid was safe and well tolerated and demonstrated potent inhibition of bone resorption. The authors believe it may improve the treatment of metastatic bone disease. Cancer 2001;91:144–54. © 2001 American Cancer Society.