Supportive Care in Cancer

, Volume 12, Issue 12, pp 877–881

Rapid administration of ibandronate does not affect renal functioning: evidence from clinical studies in metastatic bone disease and hypercalcaemia of malignancy

Short Communication

Abstract

Ibandronate is a third-generation aminobisphosphonate that has an excellent safety record in hypercalcaemia of malignancy, and has recently been approved for the prevention of skeletal events from metastatic breast cancer. This paper reviews the safety data from clinical studies of intravenous ibandronate by infusion or injection, focusing on renal adverse events (AEs). In clinical trials of patients with hypercalcaemia of malignancy, 2-h infusions of ibandronate at doses of up to 6 mg had a low potential for renal events. In a phase III trial of patients with metastatic bone disease from breast cancer, 6 mg ibandronate infused over 1–2 h had a renal safety profile comparable to that of placebo. In pilot studies, repeated daily infusions of ibandronate (4 mg infused over 2 h for four consecutive days, or 6 mg infused over 1 h for three consecutive days) for severe metastatic bone pain were not associated with any renal AEs. The safety of single 15-min infusions of 6 mg ibandronate has been demonstrated in healthy volunteers and patients with metastatic bone disease from breast cancer or multiple myeloma. Furthermore, single and rapid bolus injections of 2 or 3 mg ibandronate did not increase the risk of renal dysfunction in patients with skeletal metastases. Implications for the renal safety of ibandronate in the management of patients with metastatic bone disease are discussed.

Keywords

Ibandronate Bisphosphonates Metastatic bone disease Renal toxicity Rapid infusion Safety 

References

  1. 1.
    Coleman RE (2001) Should bisphosphonates be the treatment of choice for metastatic bone disease? Semin Oncol 28 [Suppl 11]:35–41Google Scholar
  2. 2.
    Diel IJ, Solomayer EF, Bastert G (2000) Treatment of metastatic bone disease in breast cancer: bisphosphonates. Clin Breast Cancer 1:43–51PubMedGoogle Scholar
  3. 3.
    Pavlakis N, Stockler M (2002) Bisphosphonates for breast cancer (Cochrane Review). Update Software. The Cochrane Library. OxfordGoogle Scholar
  4. 4.
    Body JJ, Diel IJ, Lichinitser MR, Kreuser ED, Dornoff W, Gorbunova VA, Budde M, Bergström B, and the MF 4265 Study Group (2003) Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 14:1399–1405CrossRefPubMedGoogle Scholar
  5. 5.
    Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey JA, Apffelstaedt J, Hussein M, Coleman RE, Reitsma DJ, Seaman JJ, Chen BL, Ambros Y (2001) 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 7:377–387PubMedGoogle Scholar
  6. 6.
    Adami S, Zamberlan N (1996) Adverse effects of bisphosphonates. A comparative review. Drug Saf 14:158–170PubMedGoogle Scholar
  7. 7.
    Zojer N, Keck AV, Pecherstorfer M (1999) Comparative tolerability of drug therapies for hypercalcemia of malignancy. Drug Saf 21:389–406PubMedGoogle Scholar
  8. 8.
    Bounameaux HM, Schifferli J, Montani JP, Jung A, Chatelanat F (1983) Renal failure associated with intravenous disphosphonates. Lancet 1:471CrossRefGoogle Scholar
  9. 9.
    Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein MA, Coleman RE, Reitsma DJ, Chen BL, Seaman JJ (2003) 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 98:1735–1744CrossRefPubMedGoogle Scholar
  10. 10.
    Stein SH, Davidson R, Tweed A, Demichele A, Domchek S, Fox K, Cohen D (2002) Renal dysfunction with IV bisphosphonates in patients with metastatic breast cancer (abstract 2997). Proc ASCO 22:46Google Scholar
  11. 11.
    Johnson KB, Gable P, Kaime EM, Luiken G, Castillos T, Hu J (2003) Significant deterioration in renal function with the new bisphosphonate, zoledronic acid (abstract 2968). Proc ASCO 22:46Google Scholar
  12. 12.
    Markowitz GS, Fine PL, Stack JI Kunis CL, Radhakrishnan J, Palecki W, Park J, Nasr SH, Hoh S, Siegel DS, D’Agati VD (2003) Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int 64:281–289CrossRefPubMedGoogle Scholar
  13. 13.
    Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D (2003) Short-term, high-dose pamidronate-induced acute tubular necrosis: the postulated mechanisms of bisphosphonate nephrotoxicity. Am J Kidney Dis 41:E18CrossRefGoogle Scholar
  14. 14.
    Chang JT, Green L, Beitz J (2003) Renal failure with the use of zoledronic acid. N Engl J Med 349:1676–1679CrossRefPubMedGoogle Scholar
  15. 15.
    Pfister T, Atzpodien E, Bauss F (2003) The renal effects of minimally nephrotoxic doses of ibandronate and zoledronate following single and intermittent intravenous administration in rats. Toxicology 191:159–167CrossRefPubMedGoogle Scholar
  16. 16.
    Novartis (2003) Zometa product label. Novartis, Basel, SwitzerlandGoogle Scholar
  17. 17.
    Wüster C, Schöter KH, Thiébaud D, Manegold C, Krahl D, Clemens MR, Ghielmini M, Jaeger P, Scharla SH (1993) Methylpentylaminopropylidenebisphosphonate (BM 21.0955): a potent and safe bisphosphonate for the treatment of cancer-associated hypercalcemia. Bone Miner 22:77–85PubMedGoogle Scholar
  18. 18.
    Pecherstorfer M, Herrmann Z, Body JJ, Manegold C, Degardin M, Clemens MR, Thurlimann B, Tubiana-Hulin M, Steinhauer EU, van Eijkeren M, Huss HJ, Thiebaud D (1996) Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy. J Clin Oncol 14:268–276PubMedGoogle Scholar
  19. 19.
    Ralston SH, Thiébaud D, Herrmann Z, Steinhauer EU, Thurlimann B, Walls J, Lichinitser MR, Rizzolli R, Hagberg H, Huss HJ, Tubiana-Hulin M, Body JJ (1997) Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia. Br J Cancer 75:295–300PubMedGoogle Scholar
  20. 20.
    Pecherstorfer M, Steinhauer EU, Rizzoli R, Wetterwald M, Bergström B (2003) Efficacy and safety of ibandronate in the treatment of hypercalcemia of malignancy: a randomized multicentric comparison to pamidronate. Support Care Cancer 11:539–547CrossRefPubMedGoogle Scholar
  21. 21.
    Neugebauer G, Köhler W, Akinkunmi L, Pinner J, Kletzl H, Banken L (2001) Influence of peak ibandronic acid concentrations after 6 mg i.v. administration with shortened infusion time (15 and 30 minutes) on renal safety in man (abstract 486). Proc Am Soc Clin Oncol 20:122AGoogle Scholar
  22. 22.
    Body JJ, Lichinitzer M, Andreeva N, Budde M, Bergström B (2004) Safety of an intravenous (i.v.) loading dose of ibandronate followed by daily oral dosing in metastatic bone disease: results of an open-label study (abstract 735). Proc Am Soc Clin Oncol 23:60Google Scholar
  23. 23.
    Syrigos KN, Michalaki V, Mitromaras A, Pliarchopoulou F, Katirtzoglou N, Antonaki E, Roussou P (2002) Safety and efficacy of the new bisphosphonate Bondronat in the management of bone metastasis following rapid infusion. In Vivo 16:361–363PubMedGoogle Scholar
  24. 24.
    Diel I, Bell R, Tripathy D, Body JJ, Bergström B (2003) Renal safety of oral and intravenous ibandronate in metastatic bone disease: phase III clinical trial results (abstract A-106). Support Care Cancer 11:415Google Scholar
  25. 25.
    Rivkin S, Body JJ, Diel I, Bergström B (2003) Long-term safety of intravenous (i.v.) ibandronate by bolus injection or infusion for up to 4 years in metastatic bone disease: results of an open-label study. Presented at the IVth International Conference on Cancer-Induced Bone Diseases (CIBD), San Antonio, Texas, USA, 7–9 December 2003Google Scholar
  26. 26.
    Lyubimova NV, Kushlinsky NE, Lichinitser MR (2003) Long-term treatment with intravenous ibandronate does not effect renal function in breast cancer patients with metastatic bone disease (abstract A-107). Support Care Cancer 11:416Google Scholar
  27. 27.
    Mancini I, Dumon JC, Body JJ (2004) Efficacy and safety of ibandronate in the treatment of opioid-resistant bone pain associated with metastatic bone disease: a pilot study. J Clin Oncol 22: 3587-3592CrossRefGoogle Scholar
  28. 28.
    Heidenreich A, Ohlmann C, Olbert P, Hegele A (2003) High-dose ibandronate is effective and well tolerated in the treatment of pain and hypercalcaemia due to prostate cancer (abstract 897). Eur J Cancer 1:S270CrossRefGoogle Scholar
  29. 29.
    Pecherstorfer M, Ludwig H, Schlosser K, Buck S, Huss HJ, Body JJ (1996) Administration of the bisphosphonate ibandronate (BM 21.0955) by intravenous bolus injection. J Bone Miner Res 11:587–593PubMedGoogle Scholar
  30. 30.
    F. Hoffmann-La Roche (2003) Bondronat product label. F. Hoffmann-La Roche Ltd, Basel, SwitzerlandGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.First Department of Medicine and OncologyWilhelminenspitalViennaAustria
  2. 2.Centrum für ganzheitliche Gynäkologie (CGG)-Klinik GmbHMannheimGermany

Personalised recommendations