Abstract
Background and objective: Despite their widespread use in metastatic bone disease, some bisphosphonate drugs are associated with adverse events (AEs), particularly renal toxicity, adding to treatment burdens and increasing healthcare costs. Ibandronic acid is a single-nitrogen bisphosphonate with high efficacy against bone events and metastatic bone pain, and a renal safety profile comparable to that of placebo. In this study, the safety of ibandronic acid was examined over a period of 4 years.
Patients and methods: During an initial 96-week period, breast cancer patients with bone metastases were randomised in double-blind fashion to placebo or ibandronic acid 6mg administered by intravenous infusion over 1–2 hours every 3–4 weeks as part of a previously reported phase III trial (MF 4265 study). All patients completing the phase III trial were offered open-label active treatment for a further 96 weeks (extension phase). A total of 62 patients received ibandronic acid 6mg in this extension phase and were classified according to their initial treatment (placebo/ibandronic acid 6mg [placebo/6mg] and ibandronic acid 6mg/ ibandronic acid 6mg [6mg/6mg] groups). Safety was assessed by AE reports and clinical laboratory evaluations.
Results: During the 4-year study, most patients experienced at least one AE, with malignancy progression being most commonly reported. However, fewer treatment-related AEs were reported in the extension phase (placebo/6mg: 6.3% [1/16]; 6mg/6mg: 13.0% [6/46]) than in the initial phase of the study (placebo: 56.3% [9/16]; 6mg: 67.4% [31/46]). Serious AEs were mainly due to malignancy progression. There were no clinically relevant renal AEs, and in both groups, serum creatinine levels were similar for up to 4 years.
Conclusion: This 96-week open-label safety extension of a phase III, placebo-controlled trial demonstrates that long-term use of intravenous ibandronic acid is well tolerated.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Finley RS. Bisphosphonates in the treatment of bone metastases. Semin Oncol 2002; 29Suppl. 4: 132–8
Banerjee D, Asif A, Striker L, et al. Short-term, high-dose pamidronate-induced acute tubular necrosis: the postulated mechanisms of bisphosphonate nephrotoxicity. Am J Kidney Dis 2003; 41: E18
Markowitz GS, Appel GB, Fine PL, et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 2001; 12: 1164–72
Markowitz GS, Fine PL, Stack JI, et al. Toxic acute necrosis following treatment with zoledronic acid (Zometa). Kidney Int 2003; 64: 281–9
Rosen LS, Gordon D, Kaminski M, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001; 7: 377–87
Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003; 98: 1735–44
Rosen LS, Gordon D, Tchekmedyian S, et al. 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. J Clin Oncol 2003; 21: 3150–7
Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94: 1458–68
Chang JT, Green L, Beitz J. Renal failure with the use of zoledronic acid. N Engl J Med 2003; 349: 1676–9
Johnson KB, Gable P, Kaime EM, et al. Significant deterioration in renal function with the new bisphosphonate, zoledronic acid [abstract no. 2968]. J Clin Oncol 2003; 22 Suppl.: 738
Kloth DD, McDermott RS, Rogatko A, et al. Impact of zoledronic acid on renal function in patients with cancer: is constant monitoring necessary [abstract no. 3036]? J Clin Oncol 2003; 22 Suppl.: 755
Stein SH, Davidson R, Tweed A, et al. Renal dysfunction with IV bisphosphonates in patients with metastatic breast cancer [abstract no. 2997]. J Clin Oncol 2003; 22 Suppl.: 745
Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003; 21: 4042–57
De Cock E, Hutton K, Canney P, et al. Cost-effectiveness of oral ibandronic acid versus i.V. zoledronic acid and i.V. pamidronate in the treatment of metastatic bone disease in breast cancer [abstract no. 189P]. Ann Oncol 2004; 15Suppl. 3: iii 50
Bauss F, Endele R, Besenfelder E, et al. Ibandronate: serum kinetics, tissue distribution and binding to bone following intravenous bolus injection [abstract no. P-128]. Calcif Tissue Int 2002; 70: 289–90
Pfister T, Bauss F, Body JJ. The risk of cumulative renal effects of intravenous bisphosphonates [abstract no. 859P]. Ann Oncol 2004; 15Suppl. 3: iii 226
Body JJ, Diel IJ, Lichinitser MR, et al. and the MF 4265 Study Group. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 2003; 14: 1399–405
Cancer Therapy Evaluation Program. Common toxicity criteria version 2.0 [online]. DCTD, NCI, NIH, DHHS. 1999 Apr 30. Available from URL: http://ctep.cancer.gov/reporting/ctc.html [Accessed 2006 May 10]
Heidenreich A, Ohlmann C, Olbert P, et al. High-dose ibandronate is effective and well tolerated in the treatment of pain and hypercalcaemia due to metastatic urologic cancer [abstract no. 897]. Eur J Cancer 2003; 1: S270
Mancini I, Dumon JC, Body JJ. Efficacy and safety of ibandronate in the treatment of opioid-resistant bone pain associated with metastatic bone disease: a pilot study. J Clin Oncol 2004; 22: 3587–92
Ali SM, Esteva FJ, Hortobagyi G, et al. Safety and efficacy of bisphosphonates beyond 24 months in cancer patients. J Clin Oncol 2001; 19: 3434–7
Guarneri V, Donati S, Nicolini M, et al. Renal safety and efficacy of i.v. bisphosphonates in patients with skeletal metastases treated for up to 10 years. Oncologist 2005; 10: 842–8
Hutton J, De Cock E, Barrett-Lee P, et al. Cost-effectiveness of i.v. ibandronic acid versus i.v. zoledronic acid and i.v. pamidronate for metastatic bone disease from breast cancer [abstract no. 191P]. Ann Oncol 2004; 15Suppl. 3: iii 50
Body JJ, Diel IJ, Lichinitser M, et al. Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies. Br J Cancer 2004; 90: 1133–7
Pecherstorfer M, Bergström B. Safety of intravenous (i.v.) and oral ibandronate for up to 4 years in patients with metastatic breast cancer [abstract no. 186P]. Ann Oncol 2004; 15Suppl. 3: iii 49
Acknowledgements
The clinical trial and data analysis were conducted by Roche. The authors would like to thank Thomson Gardiner-Caldwell US for their editorial support.
Dr Pecherstorfer is a member of a Roche drug safety advisory board. The other authors have no conflicts of interest that are directly relevant to the contents of this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pecherstorfer, M., Rivkin, S., Body, JJ. et al. Long-Term Safety of Intravenous Ibandronic Acid for Up to 4 Years in Metastatic Breast Cancer. Clin. Drug Investig. 26, 315–322 (2006). https://doi.org/10.2165/00044011-200626060-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00044011-200626060-00002