This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berenson, J. R. Articles by Lipton, A. Search for Related Content PubMed PubMed Citation Articles by Berenson, J. R. Articles by Lipton, A.

A Phase I Dose-ranging Trial of Monthly Infusions of Zoledronic Acid for the Treatment of Osteolytic Bone Metastases¹

Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, California 90048; Jonsson Comprehensive Cancer Center, University of California School of Medicine, and Veterans Affairs Greater Los Angeles Health Care Systems, Los Angeles, California 90073 [J. R. B., R. A. V., L. S. R., J. M. V., M. W., R. S., A. S.], and Department of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033 [E. G., M. H., H. H., A. L.]

Bisphosphonates are potent inhibitors of bone resorption and provide a therapeutic benefit for patients with bone metastases. Zoledronic acid is a highly potent, nitrogen-containing bisphosphonate. In the present trial, we assessed the safety and tolerability of increasing doses of zoledronic acid and its effects on urinary markers of bone resorption in cancer patients with bone metastases. Fifty-nine cancer patients with bone metastases were enrolled sequentially into one of 8 treatment groups in the core protocol. Each patient received a 5-min i.v. infusion of 0.1, 0.2, 0.4, 0.8, 1.5, 2, 4, or 8 mg zoledronic acid monthly for 3 months. Patients were monitored for clinical findings, adverse events, electrocardiograms, markers of bone resorption, as well as routine hematology, blood chemistries, and urinalysis. Thirty patients who demonstrated a radiographic response to treatment or stable disease in the core protocol were enrolled in a humanitarian extension protocol and continued to receive monthly infusions. Zoledronic acid was well tolerated at all dose levels. Adverse events reported by >10% of patients included skeletal pain, nausea, fatigue, upper respiratory tract infection, constipation, headache, diarrhea, and fever. Three patients in the core protocol and one patient in the extension protocol experienced grade 3 skeletal pain, "flu-like" symptoms, or hypophosphatemia, which were possibly related to treatment; all recovered completely. Adverse events were reported with similar frequency across all of the dosage groups. Zoledronic acid resulted in sustained, dose-dependent decreases in urinary markers of bone resorption. Zoledronic acid was safe and well tolerated and demonstrated potent inhibition of bone resorption.

This article has been cited by other articles:

				M. R. Smith Bisphosphonates for Metastatic Bone Disease -- Too Much of a Good Thing? IBMS BoneKEy, September 1, 2006; 3(9): 24 - 27. [Full Text] [PDF]

				R. Bell Efficacy of Ibandronate in Metastatic Bone Disease: Review of Clinical Data Oncologist, October 1, 2005; 10(suppl_1): 8 - 13. [Abstract] [Full Text] [PDF]

				J. Balla The Issue of Renal Safety of Zoledronic Acid from a Nephrologist's Point of View Oncologist, May 1, 2005; 10(5): 306 - 308. [Full Text] [PDF]

				J. R. Berenson Recommendations for Zoledronic Acid Treatment of Patients with Bone Metastases Oncologist, January 1, 2005; 10(1): 52 - 62. [Abstract] [Full Text] [PDF]

				P. Conte and V. Guarneri Safety of Intravenous and Oral Bisphosphonates and Compliance With Dosing Regimens Oncologist, September 1, 2004; 9(suppl_4): 28 - 37. [Abstract] [Full Text] [PDF]

				T. Hiraga, P. J. Williams, A. Ueda, D. Tamura, and T. Yoneda Zoledronic Acid Inhibits Visceral Metastases in the 4T1/luc Mouse Breast Cancer Model Clin. Cancer Res., July 1, 2004; 10(13): 4559 - 4567. [Abstract] [Full Text] [PDF]

				J. Berenson and R. Hirschberg Safety and Convenience of a 15-Minute Infusion of Zoledronic Acid Oncologist, June 1, 2004; 9(3): 319 - 329. [Abstract] [Full Text] [PDF]

				B. Fohr, C. R. Dunstan, and M. J. Seibel Markers of Bone Remodeling in Metastatic Bone Disease J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5059 - 5075. [Abstract] [Full Text] [PDF]

				S. Yano, H. Zhang, M. Hanibuchi, T. Miki, H. Goto, H. Uehara, and S. Sone Combined Therapy with a New Bisphosphonate, Minodronate (YM529), and Chemotherapy for Multiple Organ Metastases of Small Cell Lung Cancer Cells in Severe Combined Immunodeficient Mice Clin. Cancer Res., November 1, 2003; 9(14): 5380 - 5385. [Abstract] [Full Text] [PDF]

				H L Neville-Webbe and R E Coleman The use of zoledronic acid in the management of metastatic bone disease and hypercalcaemia Palliative Medicine, September 1, 2003; 17(6): 539 - 553. [Abstract] [PDF]

				K. L. Weber and M. C. Gebhardt What's New in Musculoskeletal Oncology J. Bone Joint Surg. Am., March 31, 2003; 85(4): 761 - 767. [Full Text] [PDF]

				P. Major The Use of Zoledronic Acid, a Novel, Highly Potent Bisphosphonate, for the Treatment of Hypercalcemia of Malignancy Oncologist, December 1, 2002; 7(6): 481 - 491. [Abstract] [Full Text] [PDF]

				F. Saad, D. M. Gleason, R. Murray, S. Tchekmedyian, P. Venner, L. Lacombe, J. L. Chin, J. J. Vinholes, J. A. Goas, and B. Chen A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma J Natl Cancer Inst, October 2, 2002; 94(19): 1458 - 1468. [Abstract] [Full Text] [PDF]