Skip to main content
Log in

Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

  • Original article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Background

Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). 153Sm-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of 153Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy.

Methods

Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was ≤10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with 153Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after 153Sm-EDTMP (14 patients, group B) or within 1 month after 153Sm-EDTMP (16 patients, group C).

Results

Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either 153Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both 153Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by 153Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A (p = 0.0235). Overall median survival from the time of administration of 153Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008).

Conclusion

The results of this study confirm that 153Sm-EDTMP is effective in terms of pain relief and PSA response, with minimal toxicity. When it was administered in combination with chemotherapy, prolonged survival indicated actual clinical benefit, while there were no additive toxicities. These results provide the rationale for future prospective evaluation of combined therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5–26.

    Article  PubMed  Google Scholar 

  2. McRea LE, Karafin L. Carcinoma of the prostate: metastases, therapy, and survival—A statistical analysis of 500 cases. Int Coll Surg J 1958;29:723–8.

    Google Scholar 

  3. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996;14:1756–64.

    PubMed  CAS  Google Scholar 

  4. Sabbatini P, Larson SM, Kremer A, Zhang ZF, Sun M, Yeung H, et al. Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer. J Clin Oncol 1999;17:948–57.

    PubMed  CAS  Google Scholar 

  5. Carroll PR, Kantoff PW, Balk SP, Brown MA, D’amico AV, George DJ, et al. Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology 2002;60 suppl 1:1–6.

    Article  PubMed  Google Scholar 

  6. Chodak GW, Keane T, Klotz L. Critical evaluation of hormonal therapy for carcinoma of the prostate. Urology 2002;60:201–8.

    Article  PubMed  Google Scholar 

  7. Tannock IF. Is there evidence that chemotherapy is of benefit to patients with carcinoma of the prostate? J Clin Oncol 1985;3:1013–21.

    PubMed  CAS  Google Scholar 

  8. Eisenberger MA, Simon R, O’Dwyer PJ, Wittes RE, Friedman MA. A reevaluation of nonhormonal cytotoxic chemotherapy in treatment of prostatic carcinoma. J Clin Oncol 1985;3:827–41.

    PubMed  CAS  Google Scholar 

  9. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:1502–12.

    Article  PubMed  CAS  Google Scholar 

  10. Petrylak DP, Tangen CM, Hussain MHA, Lara PN Jr, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513–20.

    Article  PubMed  CAS  Google Scholar 

  11. Serafini AN. Therapy of metastic bone pain. J Nucl Med 2001;42:895–906.

    PubMed  CAS  Google Scholar 

  12. Lewington VJ. Bone-seeking radionuclides for therapy. J Nucl Med 2005;46:38S–47S.

    PubMed  CAS  Google Scholar 

  13. Pandit-Taskar N, Batraki M, Divgi R. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med 2004;45:1358–65.

    PubMed  CAS  Google Scholar 

  14. Dafermou A, Colamussi P, Giganti M, Cittanti C, Bestagno M, Piffanelli A. A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur J Nucl Med 2001;28:788–98.

    Article  PubMed  CAS  Google Scholar 

  15. Serafini AN. Systemic metabolic radiotherapy with samarium-153-EDTMP for the treatment of painful bone metastasis. Quart J Nucl Med 2001;45:91–9.

    CAS  Google Scholar 

  16. Serafini AN. Samarium Sm-153 lexidronam for the palliation of bone pain associated with metastasis. Cancer 2000;88 suppl:2934–9.

    Article  PubMed  CAS  Google Scholar 

  17. Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double blind placebo-controlled clinical trial. J Clin Oncol 1998;16:1574–81.

    PubMed  CAS  Google Scholar 

  18. Sartor O, Reid R, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, et al. Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 2004;63:940–5.

    Article  PubMed  Google Scholar 

  19. Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, et al. A dose-controlled study of Sm-153-EDTMP in the treatment of patients with painful bone metastasis. Eur J Cancer 1997;33:1583–91.

    Article  PubMed  CAS  Google Scholar 

  20. Sinzinger H, Weiss K, Granegger S, Ofluogu S, Kratzik CH, Hajek CH. The Vienna protocol on repeated low dose 153Sm-EDTMP therapy includes pain palliation and lesion regression/stabilization (abstract). Eur J Nucl Med 2001;28:1198.

    Google Scholar 

  21. Riva P, Franceschi G, Riva N, Casi M, Santimaria M. Anti-tumor effectiveness of multiple courses of 153Sm-EDTMP in bone metastasis from different cancers (abstract). Eur J Nucl Med 2001;28:1054.

    Google Scholar 

  22. Akerley W, Butera J, Wehbe T, Noto R, Stein B, Safran H, et al. A multiinstitutional, concurrent chemoradiation trial of strontium-89 extramustine and vinblastine for hormone refractory prostate carcinoma involving bone. Cancer 2002;94:1654–60.

    Article  PubMed  CAS  Google Scholar 

  23. Sciuto R, Festa A, Rea S, Pasqualoni R, Bergomi S, Petrilli G, et al. Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nucl Med 2002;43:79–86.

    PubMed  CAS  Google Scholar 

  24. Pagliaro LC, Delpassand ES, Williams D, Millikan RE, Tu SM, Logothetis CJ. A phase I/II study of strontium-89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases. Cancer 2003;12:2988–94.

    Article  CAS  Google Scholar 

  25. Logothetis C, Tu S, Navone N. Targeting prostate cancer bone metastases. Cancer 2003;97:785–8.

    Article  PubMed  Google Scholar 

  26. Valdés Olmos RA, Hoefnagel CA. Radionuclide therapy in oncology: the dawning of its concomitant use with other modalities? Eur J Nucl Med Mol Imaging 2004;31:929–31.

    PubMed  Google Scholar 

  27. Tu S, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, et al. Bone-targeted therapy for advanced androgen independent carcinoma of the prostate: a randomised phase II trial. Lancet 2001;367:336–41

    Article  Google Scholar 

  28. Palmedo H, Manka-Waluch A, Albers P, Schmidt-Wolf IG, Reinhardt M, Ezziddin S, et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: randomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidene-diphosphonate. J Clin Oncol 2003;21:2869–75.

    Article  PubMed  CAS  Google Scholar 

  29. Palmedo H, Bucerius J. Radionuclide therapy in oncology: repeated administrations of high dose rate radiopharmaceuticals (abstract). Eur J Nucl Med Mol Imaging 2004;31:1556.

    Article  PubMed  CAS  Google Scholar 

  30. Anderson P. Samarium for osteoblastic bone metastases and osteosarcoma. Expert Opin Pharmacother 2006;7:1475–86.

    Article  PubMed  CAS  Google Scholar 

  31. Anderson PM, Wiseman GA, Erlandson L, Rodriguez V, Trotz B, Dubansky SA, et al. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma. Clin Cancer Res 2005;11:6895–900.

    Article  PubMed  CAS  Google Scholar 

  32. Rodriguez V, Erlandson L, Arndt CAS, Wiseman GA, Anderson PM. Low toxicity and efficacy of 153samarium-EDTMP and melphalan as a conditioning regimen for secondary acute myelogenous leukemia. Pediatr Transplantation 2005;9:122–6.

    Article  Google Scholar 

  33. Knop S, Dohmer BM, Kanz L, Bares R, Einsele H. 153 Samarium-EDTMP in myeloablative dosage followed by a second autotransplantation in patients with relapsed multiple myeloma (abstract). Haematologica 2004;89:ECR36.

    PubMed  Google Scholar 

  34. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591–7.

    Article  PubMed  CAS  Google Scholar 

  35. Berry S, Waldron T, Winquist E, Lukka H. The use of bisphosphonates in men with hormone-refractory prostate cancer: a systematic review of randomized trials. Can J Urol 2006;13:3180–8.

    PubMed  Google Scholar 

  36. Storto G, Klain M, Paone G, Liuzzi R, Molino L, Marinelli A, et al. Combined therapy with Sr-89 and zoledronic acid in patients with painful bone metastases. Bone 2006;39:35–41.

    Article  PubMed  CAS  Google Scholar 

  37. Laplanche A, Beuzeboc P, Lumbroso J, Di Palma M, Theodore C, Prapotnich D, et al. A phase II trial of docetaxel and samarium in patients with bone metastases from castration-refractory prostate cancer (CRPC) and a response or stabilization after induction docetaxel-estramustine (abstract). Proc Am Soc Clin Oncol 2006;24:4608.

    Google Scholar 

  38. Widmark A, Linne T, Modig H, Johansson L. Optimizing the time of co-administration of docetaxel and samarium-153 for advanced androgen independent carcinoma of the prostate (abstract). Proc Am Soc Clin Oncol 2003;22:433.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Giuliano Mariani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ricci, S., Boni, G., Pastina, I. et al. Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer. Eur J Nucl Med Mol Imaging 34, 1023–1030 (2007). https://doi.org/10.1007/s00259-006-0343-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-006-0343-8

Keywords

Navigation