Supportive Care in Cancer

, Volume 17, Issue 6, pp 719–725

Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review

  • Ingo J. Diel
  • Rudolf Weide
  • Hubert Köppler
  • Lucia Antràs
  • Michael Smith
  • Jesse Green
  • Neil Wintfeld
  • Maureen Neary
  • Mei Sheng Duh
Original Article

Abstract

Purpose

This retrospective study compared renal impairment rates in breast cancer, multiple myeloma, prostate cancer and non-small cell lung cancer patients treated with ibandronate or zoledronic acid.

Study design

Medical records in two German oncology clinics from May 2001 to March 2006 were retrospectively reviewed. Creatinine measurements were analyzed from baseline (before bisphosphonate treatment) to last available measurement for each patient. The Cox proportional hazards model and the Andersen–Gill extension of the Cox model for multiple events analysis were used for multivariate analysis, which controlled for age, clinic site, primary cancer type, baseline SCr or GFR value, prior bisphosphonate use, concomitant use of drugs associated with acute renal failure, and renal-related comorbidities.

Results

Of 333 patients, 109 received ibandronate and 256 received zoledronic acid (32 patients had both drugs). Compared with ibandronate, the zoledronic acid group had a significantly better baseline renal function and fewer patients had a history of renal disease. Zoledronic acid treatment increased the relative risk (RR) and the incidence rate (IR) of renal impairment by ~1.5-fold in all assessed patients (all tumors) compared with ibandronate. Multivariate analysis found significantly higher hazards ratios for zoledronic acid over ibandronate (two to sixfold), after adjusting for differences in characteristics between the two treatment groups.

Conclusions

In this retrospective review, patients were significantly more likely to experience renal impairment with zoledronic acid than with ibandronate.

Keywords

Zoledronic acid Ibandronate Renal impairment Medical records Creatinine clearance 

References

  1. 1.
    Berenson J, Hirschberg R (2004) Safety and convenience of a 15-minute infusion of zoledronic acid. Oncologist 9:319–329PubMedCrossRefGoogle Scholar
  2. 2.
    Bergner R, Diel IJ, Henrich D, Hoffmann M, Uppenkamp M (2006) Differences in nephrotoxicity of intravenous bisphosphonates for the treatment of malignancy-related bone disease. Onkologie 29:534–540 doi:10.1159/000096056 PubMedCrossRefGoogle Scholar
  3. 3.
    Body JJ, Diel IJ, Lichinitser MR et al (2003) Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 14:1399–1405PubMedCrossRefGoogle Scholar
  4. 4.
    Body JJ, Diel IJ, Lichinitzer M et al (2004) 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 90:1133–1137PubMedCrossRefGoogle Scholar
  5. 5.
    Body JJ, Diel IJ, Tripathy D, Bergström B (2006) Intravenous ibandronate does not affect time to renal function deterioration in patients with skeletal metastases from breast cancer: phase III trial results. Eur J Cancer Care (Engl) 15:299–302CrossRefGoogle Scholar
  6. 6.
    Body JJ, Lichinitser M, Tjulandin S, Bergström B (2006) Oral ibandronate and intravenous zoledronic acid in metastatic breast cancer patients: comparative bone turnover marker and safety data [abstract 68]. Bone 38(3 Suppl.1):S69Google Scholar
  7. 7.
    Chang JT, Green L, Beitz J (2003) Renal failure with the use of zoledronic acid. N Engl J Med 349:1676–1679PubMedCrossRefGoogle Scholar
  8. 8.
    Chern B, Joseph D, Joshua D et al (2004) Bisphosphonate infusions: patient preference, safety and clinic use. Support Care Cancer 12:463–466PubMedCrossRefGoogle Scholar
  9. 9.
    Cramer JA, Amonkar MM, Hebborn A, Altman R (2005) Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin 21:1453–1460PubMedCrossRefGoogle Scholar
  10. 10.
    Diel IJ, Weide R, Köppler H et al (2006) Renal impairment in cancer patients following zoledronic acid or ibandronate treatment [abstract 1002P]. Ann Oncol 17(Suppl.9):78Google Scholar
  11. 11.
    Eastell R, Garnero P, Vrijens B et al (2006) Influence of patient compliance with risedronate therapy on bone turnover marker and bone mineral density response: the IMPACT study. Calcif Tissue Int 72:408Google Scholar
  12. 12.
    Ezra A, Golomb B (2000) Administration routes and delivery systems of bisphosphonates for the treatment of bone resorption. Adv Drug Deliv Rev 42:175–195PubMedCrossRefGoogle Scholar
  13. 13.
    Green JR, Müller K, Jaeggi KA (1994) Preclinical pharmacology of CGP 42'446, a new, potent, heterocyclic bisphosphonate compound. J Bone Miner Res 9:745–751PubMedGoogle Scholar
  14. 14.
    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 metastatic urologic cancer. Eur J Cancer 1(Suppl.5):S270Google Scholar
  15. 15.
    Henrich D, Bergner R, Hoffman M et al (2005) Open-label study of ibandronate in elderly myeloma patients with pre-existing renal deterioration [abstract 3459]. Blood 106:11CrossRefGoogle Scholar
  16. 16.
    Johnson KB, Gable P, Kaine EM et al (2003) Significant deterioration in renal function with the new bisphosphonate zoledronic acid [abstract 2968]. J Clin Oncol 22(Suppl.):738Google Scholar
  17. 17.
    Kristensen B, Ejlertsen B, Groenvold M et al (1999) Oral clodronate in breast cancer patients with bone metastases: a randomized study. J Intern Med 246:67–64PubMedCrossRefGoogle Scholar
  18. 18.
    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470PubMedGoogle Scholar
  19. 19.
    Lyubimova NV, Kushlinsky NE, Lichinister MR Schlosser K (2003) Renal safety of intravenous ibandronic acid in breast cancer patients with metastatic bone disease. Clin Drug Invest 23:707–716CrossRefGoogle Scholar
  20. 20.
    Major P, Lortholary A, Hon J et al (2001) Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 19:558–567PubMedGoogle Scholar
  21. 21.
    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 22:3587–3592PubMedCrossRefGoogle Scholar
  22. 22.
    Markowitz GS, Fine PL, Stack JI et al (2003) Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int 64:281–289PubMedCrossRefGoogle Scholar
  23. 23.
    Mazj S, Lichtman SM (2004) Renal dysfunction associated with bisphosphonate use: retrospective analysis of 293 patients with respect to age and other clinical characteristics [abstract 8039]. J Clin Oncol 22(Suppl.):735Google Scholar
  24. 24.
    Mühlbauer RC, Bauss F, Schenk R et al (1991) BM 21.0955, a potent new bisphosphonate to inhibit bone resorption. J Bone Miner Res 6:1003–1011PubMedCrossRefGoogle Scholar
  25. 25.
    Munier A, Gras V, Andrejak M et al (2005) Zoledronic acid and renal toxicity: data from French adverse effect reporting database. Ann Pharmacother 39:1194–1197PubMedCrossRefGoogle Scholar
  26. 26.
    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 191:159–167PubMedCrossRefGoogle Scholar
  27. 27.
    Pfister T, Atzpodien E, Bohrmann B, Bauss F (2005) Acute renal effects of intravenous bisphosphonates in the rat. Basic Clin Pharmacol Toxicol 97:374–381PubMedCrossRefGoogle Scholar
  28. 28.
    Reginster JY, Rabenda V (2006) Patient preference in the management of postmenopausal osteoporosis with bisphosphonates. Clin Interv Aging 1:415–423PubMedCrossRefGoogle Scholar
  29. 29.
    Rosen LS, Gordon D, Kaminski M et al (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 98:1735–1744PubMedCrossRefGoogle Scholar
  30. 30.
    Taggart H, Bolognese MA, Lindsay R et al (2002) Upper gastrointestinal tract safety of risedronate: a pooled analysis of 9 clinical trials. Mayo Clin Proc 77:262–270PubMedCrossRefGoogle Scholar
  31. 31.
    Thadhani R, Pascual M, Bonventre JV (1996) Acute renal failure. N Engl J Med 334:1448–1460PubMedCrossRefGoogle Scholar
  32. 32.
    von Moos R, Caspar CB, Angst R et al (2006) Renal safety of intravenous ibandronate 6 mg infused over 15 minutes or 60 minutes in patients with breast cancer and bone metastases [abstract 1078]Google Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ingo J. Diel
    • 1
  • Rudolf Weide
    • 2
  • Hubert Köppler
    • 2
  • Lucia Antràs
    • 3
  • Michael Smith
    • 3
  • Jesse Green
    • 4
  • Neil Wintfeld
    • 4
  • Maureen Neary
    • 5
  • Mei Sheng Duh
    • 3
  1. 1.Centrum für ganzheitliche GynäkologieMannheimGermany
  2. 2.Praxisklinik für Hämatologie und Onkologie KoblenzKoblenzGermany
  3. 3.Analysis Group, Inc.BostonUSA
  4. 4.F. Hoffmann-La Roche, Inc.NutleyUSA
  5. 5.GlaxoSmithKlineDurhamUSA

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