This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rosen, L. S. Articles by Seaman, J. J. Search for Related Content PubMed PubMed Citation Articles by Rosen, L. S. Articles by Seaman, J. J.

Zoledronic Acid Versus Placebo in the Treatment of Skeletal Metastases in Patients With Lung Cancer and Other Solid Tumors: A Phase III, Double-Blind, Randomized Trial—The Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group

From the Cancer Institute Medical Group, Santa Monica; Pacific Shores Medical Group, Long Beach; and Gilroy, CA. US Oncology, San Antonio, TX. McGill Department of Oncology, Montreal, Quebec, Canada. The M. Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw; and Klinika Chemotherapii Centrum Onkologii, Krakow, Poland. St George Hospital Cancer Care Center, Kogarah, Australia. Novartis Pharmaceuticals Corp, East Hanover, NJ.

Address reprint requests to Lee S. Rosen, MD, Cancer Institute Medical Group, 11818 Wilshire Blvd, Suite 200, Los Angeles, CA 90025; email: lrosen{at}cimg.org.

Purpose: To assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to solid tumors other than breast or prostate cancer.

Patients and Methods: Patients were randomly assigned to receive zoledronic acid (4 or 8 mg) or placebo every 3 weeks for 9 months, with concomitant antineoplastic therapy. The 8-mg dose was reduced to 4 mg (8/4-mg group). The primary efficacy analysis was proportion of patients with at least one skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy to bone, and surgery to bone. Secondary analyses (time to first SRE, skeletal morbidity rate, and multiple event analysis) counted hypercalcemia as an SRE.

Results: Among 773 patients with bone metastases from lung cancer or other solid tumors, the proportion with an SRE was reduced in both zoledronic acid groups compared with the placebo group (38% for 4 mg and 35% for 8/4 mg zoledronic acid v 44% for the placebo group; P = .127 and P = .023 for 4-mg and 8/4-mg groups, respectively). Additionally, 4 mg zoledronic acid significantly increased time to first event (median, 230 v 163 days for placebo; P = .023), an important end point in this poor-prognosis population, and significantly reduced the risk of developing skeletal events by multiple event analysis (hazard ratio = 0.732; P = .017). Zoledronic acid was well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and vomiting.

Conclusion: Zoledronic acid (4 mg infused over 15 minutes) is the first bisphosphonate to reduce skeletal complications in patients with bone metastases from solid tumors other than breast and prostate cancer.

This article has been cited by other articles:

				H. M. Weiss, U. Pfaar, A. Schweitzer, H. Wiegand, A. Skerjanec, and H. Schran Biodistribution and Plasma Protein Binding of Zoledronic Acid Drug Metab. Dispos., October 1, 2008; 36(10): 2043 - 2049. [Abstract] [Full Text] [PDF]

				C. I. Ripamonti, M. Maniezzo, T. Campa, E. Fagnoni, C. Brunelli, G. Saibene, C. Bareggi, L. Ascani, and E. Cislaghi Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan Ann. Onc., July 22, 2008; (2008) mdn526v1. [Abstract] [Full Text] [PDF]

				B. Freidlin, E. L. Korn, R. Gray, and A. Martin Multi-Arm Clinical Trials of New Agents: Some Design Considerations Clin. Cancer Res., July 15, 2008; 14(14): 4368 - 4371. [Abstract] [Full Text] [PDF]

				M. Aapro, P. A. Abrahamsson, J. J. Body, R. E. Coleman, R. Colomer, L. Costa, L. Crino, L. Dirix, M. Gnant, J. Gralow, et al. Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel Ann. Onc., March 1, 2008; 19(3): 420 - 432. [Abstract] [Full Text] [PDF]

				T. Ibrahim, F. Barbanti, G. Giorgio-Marrano, L. Mercatali, S. Ronconi, C. Vicini, and D. Amadori Osteonecrosis of the Jaw in Patients with Bone Metastases Treated with Bisphosphonates: A Retrospective Study Oncologist, March 1, 2008; 13(3): 330 - 336. [Abstract] [Full Text] [PDF]

				I. Sekine, M. Sumi, and N. Saijo Local Control of Regional and Metastatic Lesions and Indication for Systemic Chemotherapy in Patients with Non-Small Cell Lung Cancer Oncologist, January 1, 2008; 13(suppl_1): 21 - 27. [Abstract] [Full Text] [PDF]

				K. Olson and C. Van Poznak Significance and impact of bisphosphonate-induced acute phase responses Journal of Oncology Pharmacy Practice, December 1, 2007; 13(4): 223 - 229. [Abstract] [PDF]

				P. A. Kvale, P. A. Selecky, and U. B. S. Prakash Palliative Care in Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition) Chest, September 1, 2007; 132(3_suppl): 368S - 403S. [Abstract] [Full Text] [PDF]

				D. Santini, B. Vincenzi, S. Galluzzo, F. Battistoni, L. Rocci, O. Venditti, G. Schiavon, S. Angeletti, F. Uzzalli, M. Caraglia, et al. Repeated Intermittent Low-Dose Therapy with Zoledronic Acid Induces an Early, Sustained, and Long-Lasting Decrease of Peripheral Vascular Endothelial Growth Factor Levels in Cancer Patients Clin. Cancer Res., August 1, 2007; 13(15): 4482 - 4486. [Abstract] [Full Text] [PDF]

				D Aguiar Bujanda, U Bohn Sarmiento, M. Cabrera Suarez, and J Aguiar Morales Assessment of renal toxicity and osteonecrosis of the jaws in patients receiving zoledronic acid for bone metastasis Ann. Onc., March 1, 2007; 18(3): 556 - 560. [Abstract] [Full Text] [PDF]

				D. Rades, T. Veninga, L. J.A. Stalpers, H. Basic, V. Rudat, J. H. Karstens, J. Dunst, and S. E. Schild Outcome After Radiotherapy Alone for Metastatic Spinal Cord Compression in Patients With Oligometastases J. Clin. Oncol., January 1, 2007; 25(1): 50 - 56. [Abstract] [Full Text] [PDF]

				C. Gridelli The Use of Bisphosphonates in Elderly Cancer Patients Oncologist, January 1, 2007; 12(1): 62 - 71. [Abstract] [Full Text] [PDF]

				M. L de Lemos, S. C Taylor, J. B Barnett, F. Hu, A. Levin, V. Moravan, and S. E O'Reilly Renal safety of 1-hour pamidronate infusion for breast cancer and multiple myeloma patients: comparison between clinical trials and population-based database Journal of Oncology Pharmacy Practice, December 1, 2006; 12(4): 193 - 199. [Abstract] [PDF]

				R. E. Coleman Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin. Cancer Res., October 15, 2006; 12(20): 6243s - 6249s. [Abstract] [Full Text] [PDF]

				D. Cameron, M. Fallon, and I. Diel Ibandronate: Its Role in Metastatic Breast Cancer Oncologist, September 1, 2006; 11(suppl_1): 27 - 33. [Abstract] [Full Text] [PDF]

				T. Tanvetyanon and P. J. Stiff Management of the adverse effects associated with intravenous bisphosphonates Ann. Onc., June 1, 2006; 17(6): 897 - 907. [Abstract] [Full Text] [PDF]

				A. Bamias, E. Kastritis, C. Bamia, L. A. Moulopoulos, I. Melakopoulos, G. Bozas, V. Koutsoukou, D. Gika, A. Anagnostopoulos, C. Papadimitriou, et al. Osteonecrosis of the Jaw in Cancer After Treatment With Bisphosphonates: Incidence and Risk Factors J. Clin. Oncol., December 1, 2005; 23(34): 8580 - 8587. [Abstract] [Full Text] [PDF]

				M. D. MELO and G. OBEID Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: Strategies for prevention and early recognition J Am Dent Assoc, December 1, 2005; 136(12): 1675 - 1681. [Abstract] [Full Text] [PDF]

				M. D. Michaelson and M. R. Smith Bisphosphonates for Treatment and Prevention of Bone Metastases J. Clin. Oncol., November 10, 2005; 23(32): 8219 - 8224. [Abstract] [Full Text] [PDF]

				J.-J. Body Bisphosphonates in Metastatic Bone Disease: Renal Safety Matters Oncologist, October 1, 2005; 10(suppl_1): 1 - 2. [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]

				G A Clines and T A Guise Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone Endocr. Relat. Cancer, September 1, 2005; 12(3): 549 - 583. [Abstract] [Full Text] [PDF]

				N. Kohno, K. Aogi, H. Minami, S. Nakamura, T. Asaga, Y. Iino, T. Watanabe, C. Goessl, Y. Ohashi, and S. Takashima Zoledronic Acid Significantly Reduces Skeletal Complications Compared With Placebo in Japanese Women With Bone Metastases From Breast Cancer: A Randomized, Placebo-Controlled Trial J. Clin. Oncol., May 20, 2005; 23(15): 3314 - 3321. [Abstract] [Full Text] [PDF]

				P. Conte and V. Guarneri In Response to Jackson Letter to the Editor Regarding "Safety of Intravenous and Oral Bisphosphonates and Compliance with Dosing Regimens" Oncologist, May 1, 2005; 10(5): 315 - 316. [Full Text] [PDF]

				N. Pandeya, D. M. Purdie, A. Green, and G. Williams Repeated Occurrence of Basal Cell Carcinoma of the Skin and Multifailure Survival Analysis: Follow-up Data from the Nambour Skin Cancer Prevention Trial Am. J. Epidemiol., April 15, 2005; 161(8): 748 - 754. [Abstract] [Full Text] [PDF]

				J. E. Brown, R. J. Cook, P. Major, A. Lipton, F. Saad, M. Smith, K.-A. Lee, M. Zheng, Y.-J. Hei, and R. E. Coleman Bone Turnover Markers as Predictors of Skeletal Complications in Prostate Cancer, Lung Cancer, and Other Solid Tumors J Natl Cancer Inst, January 5, 2005; 97(1): 59 - 69. [Abstract] [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]

				J. Berenson and R. Hirschberg In Response to Diel I, Bergner R. Letter to the Editor of The Oncologist Re: Safety and Convenience of a 15-Minute Infusion of Zoledronic Acid Oncologist, January 1, 2005; 10(1): 84 - 87. [Full Text] [PDF]

				C. L. Vogel, R. H. Yanagihara, A. J. Wood, F. M. Schnell, C. Henderson, B. H. Kaplan, M. H. Purdy, R. Orlowski, J. L. Decker, L. Lacerna, et al. Safety and Pain Palliation of Zoledronic Acid in Patients with Breast Cancer, Prostate Cancer, or Multiple Myeloma Who Previously Received Bisphosphonate Therapy Oncologist, November 1, 2004; 9(6): 687 - 695. [Abstract] [Full Text] [PDF]

				A. Lipton, A. Colombo-Berra, R. M. Bukowski, L. Rosen, M. Zheng, and G. Urbanowitz Skeletal Complications in Patients with Bone Metastases from Renal Cell Carcinoma and Therapeutic Benefits of Zoledronic Acid Clin. Cancer Res., September 15, 2004; 10(18): 6397S - 6403S. [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]

				N. Pandit-Taskar, M. Batraki, and C. R. Divgi Radiopharmaceutical Therapy for Palliation of Bone Pain from Osseous Metastases J. Nucl. Med., August 1, 2004; 45(8): 1358 - 1365. [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]

				T. Tanvetyanon and A. M Choudhury Hypocalcemia and Azotemia Associated with Zoledronic Acid and Interferon Alfa Ann. Pharmacother., March 1, 2004; 38(3): 418 - 421. [Abstract] [Full Text] [PDF]

				D. M. Brundage Cancer Pain Management in Adults: A Pharmacist's Perspective Journal of Pharmacy Practice, August 1, 2003; 16(4): 284 - 290. [Abstract] [PDF]