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Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

153Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet®) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa®) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated.

Methods

Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg 153Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before 153Sm-EDTMP treatment. Urine was collected 48 h after injection of 153Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of 153Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied.

Results

The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 ± 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 ± 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with 153Sm-EDTMP.

Conclusion

Zoledronic acid treatment does not influence 153Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe.

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Acknowledgements

We thank Alice van Dongen for her input. This study was financially supported by CIS bio International, Saclay, France. Zoledronic acid was kindly provided by Novartis, Stein, Switzerland.

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This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands

    Marnix G. E. H. Lam & Peter P. van Rijk

  2. CIS bio International, Saclay, France

    Amel Dahmane & Wil H. M. Stevens

  3. Department of Nuclear Medicine, Meander Medical Center, Amersfoort, The Netherlands

    John M. H. de Klerk

  4. Department of Internal Medicine, UMC Utrecht, Utrecht, The Netherlands

    Bernard A. Zonnenberg

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  1. Marnix G. E. H. Lam
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  2. Amel Dahmane
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Correspondence to Marnix G. E. H. Lam.

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Lam, M.G., Dahmane, A., Stevens, W.H.M. et al. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases. Eur J Nucl Med Mol Imaging 35, 756–765 (2008). https://doi.org/10.1007/s00259-007-0659-z

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  • DOI: https://doi.org/10.1007/s00259-007-0659-z

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