177Lu-EDTMP for palliation of pain from bone metastases in patients with prostate and breast cancer: a phase II study

  • Krishan Kant Agarwal
  • Suhas Singla
  • Geetanjali Arora
  • Chandrasekhar BalEmail author
Original Article



The purpose of this study was to evaluate the efficacy and safety of 177Lu-EDTMP for pain palliation in patients with bone metastases from castration-resistant prostate and breast cancer. The secondary objective was to compare low-dose and high-dose 177Lu-EDTMP in bone pain palliation.


Included in the study were 44 patients with documented breast carcinoma (12 patients; age 47 ± 13 years) or castration-resistant prostate carcinoma (32 patients; age 66 ± 9 years) and skeletal metastases. Patients were randomized into two equal groups treated with 177Lu-EDTMP intravenously at a dose of 1,295 MBq (group A) or 2,590 MBq (group B). Pain palliation was evaluated using a visual analogue score (VAS), analgesic score (AS) and Karnofsky performance score (KPS) up to 16 weeks. Toxicity was assessed in terms of haematological and renal parameters.


The overall response rate (in all 44 patients) was 86 %. Complete, partial and minimal responses were seen in 6 patients (13 %), 21 patients (48 %) and 11 patients (25 %), respectively. A favourable response was seen in 27 patients (84 %) with prostate cancer and in 11 patients (92 %) with breast cancer. There was a progressive decrease in the VAS from baseline up to 4 weeks (p < 0.05). Also, AS decreased significantly from 1.8 ± 0.7 to 1.2 ± 0.9 (p < 0.0001). There was an improvement in quality of life of the patients as reflected by an increase in mean KPS from 56 ± 5 to 75 ± 7 (p < 0.0001). The overall response rate in group A was 77 % compared to 95 % in group B (p = 0.188). There was a significant decrease in VAS and AS accompanied by an increase in KPS in both groups. Nonserious haematological toxicity (grade I/II) was observed in 15 patients (34 %) and serious toxicity (grade III/IV) occurred in 10 patients (23 %). There was no statistically significant difference in haematological toxicity between the groups.


177Lu-EDTMP was found to be a safe and effective radiopharmaceutical for bone pain palliation in patients with metastatic prostate and breast carcinoma. There were no differences in efficacy or toxicity between patients receiving low-dose and high-dose 177Lu-EDTMP.


177Lu-EDTMP Breast and prostate carcinoma Pain palliation Low dose High dose 



We are grateful to Dr. John J. Zaknun, MD, Nuclear Medicine Section, Division of Human Health, International Atomic Energy Agency, Vienna, Austria, and Dr. Meera Venkatesh, Dr. Sudipta Chakraborty, Dr. Tapas Das, Dr. Sharmila Banerjee and Dr. M.R.A. Pillai, Radiopharmaceutical Division, Bhabha Atomic Research Centre, Mumbai, for their support in completion of the research.

Conflicts of interest



No funding received from any organization for this study.


  1. 1.
    Galasko CS. Diagnosis of skeletal metastases and assessment of response to treatment. Clin Orthop Relat Res. 1995;312:64–75.PubMedGoogle Scholar
  2. 2.
    Barnes EA. Radiopharmaceuticals for painful bone metastases: perspective from radiation oncology. J Support Oncol. 2011;9:208–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Fischer M, Kampen WU. Radionuclide therapy of bone metastases. Breast Care (Basel). 2012;7:100–7.CrossRefGoogle Scholar
  4. 4.
    Shah Syed GM, Maken RN, Muzzaffar N, Shah MA, Rana F. Effective and economical option for pain palliation in prostate cancer with skeletal metastases: 32P therapy revisited. Nucl Med Commun. 1999;20:697–702.PubMedCrossRefGoogle Scholar
  5. 5.
    Fang N, Li Y, Xu YS, Ma D, Fu P, Gao HQ, et al. Serum concentrations of IL-2 and TNF-alpha in patients with painful bone metastases: correlation with responses to 89SrCl2 therapy. J Nucl Med. 2006;47:242–6.PubMedGoogle Scholar
  6. 6.
    Maini CL, Bergomi S, Romano L, Sciuto R. 153Sm-EDTMP for bone pain palliation in skeletal metastases. Eur J Nucl Med Mol Imaging. 2004;31 Suppl 1:S171–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Porter AT, McEwan AJ, Powe JE, Reid R, McGowan DG, Lukka H, et al. Results of a randomized phase III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys. 1993;25:805–13.PubMedCrossRefGoogle Scholar
  8. 8.
    Tu SM, 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;357:336–41.PubMedCrossRefGoogle Scholar
  9. 9.
    Sciuto R, Festa A, Rea S, Pasqualoni R, Bergomi S, Petrilli G, et al. Effects of low-dose cisplatin on strontium-89 therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J Nucl Med. 2002;43:79–86.PubMedGoogle Scholar
  10. 10.
    Chakraborty S, Das T, Banerjee S, Balogh L, Chaudhari PR, Sarma HD, et al. 177Lu-EDTMP: a viable bone pain palliative in skeletal metastasis. Cancer Biother Radiopharm. 2008;23:202–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Máthé D, Balogh L, Polyák A, Király R, Márián T, Pawlak D, et al. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent. Nucl Med Biol. 2010;37:215–26.PubMedCrossRefGoogle Scholar
  12. 12.
    Chakraborty S, Das T, Unni PR, Sarma HD, Samuel G, Banerjee S, et al. 177Lu-labeled polyaminophosphonates as potential agents for bone pain palliation. Nucl Med Commun. 2002;23:67–74.PubMedCrossRefGoogle Scholar
  13. 13.
    Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs. 1992;10:239–53.PubMedCrossRefGoogle Scholar
  14. 14.
    McCaffery M, Pasero C. Pain: clinical manual. St. Louis: Mosby; 1999. p. 16.Google Scholar
  15. 15.
    Crooks V, Waller S, Smith T, Hahn TJ. The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients. J Gerontol. 1991;46:M139–44.PubMedCrossRefGoogle Scholar
  16. 16.
    Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systemic review. Lancet Oncol. 2005;6:392–400.PubMedCrossRefGoogle Scholar
  17. 17.
    Hoskin PJ, Stratford MR, Folkes LK, Regan J, Yarnold JR. Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity. Lancet. 2000;355:1428–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Parker CC, Pascoe S, Chodacki A, O’Sullivan JM, Germá JR, O’Bryan-Tear CG, et al. A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer. Eur Urol. 2013;63:189–97.PubMedCrossRefGoogle Scholar
  19. 19.
    Nilsson S, Franzen L, Parker C, Tyrrell C, Blom R, Tennvall J, et al. Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases. Clin Genitourin Cancer. 2013;11:20–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Abbasi IA. Studies on 177Lu-labeled methylene diphosphonate as potential bone-seeking radiopharmaceutical for bone pain palliation. Nucl Med Biol. 2011;38:417–25.PubMedCrossRefGoogle Scholar
  21. 21.
    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 hydroxyethylidenediphosphonate. J Clin Oncol. 2003;21:2869–75.PubMedCrossRefGoogle Scholar
  22. 22.
    Kolesnikov-Gauthier H, Carpentier P, Depreux P, Vennin P, Caty A, Sulman C, et al. Evaluation of toxicity and efficacy of 186Re-hydroxyethylidene diphosphonate in patients with painful bone metastases of prostate or breast cancer. J Nucl Med. 2000;41:1689–94.PubMedGoogle Scholar
  23. 23.
    Pons F, Herranz R, Garcia A, Vidal-Sicart S, Conill C, Grau JJ, et al. Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer. Eur J Nucl Med. 1997;24:1210–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Collins C, Eary JF, Donaldson G, Vernon C, Bush NE, Petersdorf S, et al. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial. J Nucl Med. 1993;34:1839–44.PubMedGoogle Scholar
  25. 25.
    Ahonen A, Joensuu H, Hiltunen J, Hannelin M, Heikkila J, Jakobsson M, et al. Samarium-153-EDTMP in bone metastases. J Nucl Biol Med. 1994;38:123–7.PubMedGoogle Scholar
  26. 26.
    Smith MR, Kabbinavar F, Saad F, Hussain A, Gittelman MC, Bilhartz DL, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23:2918–25.PubMedCrossRefGoogle Scholar
  27. 27.
    Yuan J, Liu C, Liu X, Wang Y, Kuai D, Zhang G, et al. Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer a phase II study. Clin Nucl Med. 2013;38:88–92.PubMedCrossRefGoogle Scholar
  28. 28.
    Liepe K, Kotzerke J. A comparative study of 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr in the treatment of painful skeletal metastases. Nucl Med Commun. 2007;28:623–30.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Krishan Kant Agarwal
    • 1
  • Suhas Singla
    • 1
  • Geetanjali Arora
    • 1
  • Chandrasekhar Bal
    • 1
    Email author
  1. 1.Department of Nuclear MedicineAll India Institute of Medical SciencesNew DelhiIndia

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