Advertisement

memo - Magazine of European Medical Oncology

, Volume 11, Issue 4, pp 301–304 | Cite as

Lutetium-PSMA therapy—a new therapeutic option in metastatic castration-resistant prostate cancer?

  • Michael Ladurner
  • Wolfgang Horninger
  • Jasmin Bektic
short review
  • 20 Downloads

Summary

Although localized prostate cancer (PC) is a curable disease, a significant proportion of patients progress from advanced PC to metastatic castration-resistant prostate cancer (mCRPC). Several new treatments for mCRPC were approved including new hormonal therapies, chemotherapies, and radium-223. For patients with disease progression after the standard therapies, lutetium-prostate-specific membrane antigen (Lu-PSMA) therapy could be an option.

The aim of this short review is to give an overview of the available evidence of the efficacy and toxicity of Lu-PSMA therapy. To date, one prospective phase II trial and several small retrospective studies have been published including almost 400 patients. Primary endpoint of all available trials was a decline in PSA of >50%, which was achieved in 30–70% of men treated with Lu-PSMA therapy. A PSA decline was observed in 70–91% of cases. Overall survival was reported only in small retrospective subgroups, and no prospective data are available. Progressive disease was observed in 11–32% of patients after Lu-PSMA treatment.

Lu-PSMA treatment seems to be well tolerated and safe. One common treatment-related grade 1 adverse event is dry mouth in up to 87% of men after radioligand therapy (RLT). Therefore, in the vast majority no treatment is needed. Hematologic toxicity such as thrombocytopenia caused serious grade 3–4 adverse events in 27% of patients in the prospective trial. No immediate adverse events after radioligand infusion and no treatment-related deaths were reported.

According to preliminary data, Lu-PSMA therapy seems to be well tolerated and safe for progressive end-stage mCRPC patients. Further prospective trials are needed.

Keywords

Prostate cancer Lutetium PSMA Radioligand therapy mCRPC 

Notes

Conflict of interest

M. Ladurner, W. Horninger, and J. Bektic declare that they have no competing interests.

References

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E86.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12.CrossRefPubMedGoogle Scholar
  3. 3.
    de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147–54.CrossRefPubMedGoogle Scholar
  4. 4.
    de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–97.CrossRefGoogle Scholar
  6. 6.
    Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–23.CrossRefPubMedGoogle Scholar
  7. 7.
    Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138–48.CrossRefGoogle Scholar
  8. 8.
    Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424–33.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Santoni M, Scarpelli M, Mazzucchelli R, et al. Targeting prostate-specific membrane antigen for personalized therapies in prostate cancer: morphologic and molecular backgrounds and future promises. J Biol Regul Homeost Agents. 2014;28(4):555–63.PubMedGoogle Scholar
  10. 10.
    Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3(1):81–5.PubMedGoogle Scholar
  11. 11.
    Sheikhbahaei S, Afshar-Oromieh A, Eiber M, et al. Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging. Eur J Nucl Med Mol Imaging. 2017;44(12):2117–36.CrossRefPubMedGoogle Scholar
  12. 12.
    Spatz S, Tolkach Y, Jung K, et al. Comprehensive evaluation of prostate specific membrane antigen expression in the vasculature of renal tumors: implications for imaging studies and prognostic role. J Urol. 2018;199(2):370–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Kabasakal L, AbuQbeitah M, Aygun A, et al. Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(13):1976–83.CrossRefPubMedGoogle Scholar
  14. 14.
    Wright GL Jr., Haley C, Beckett ML, Schellhammer PF. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1(1):18–28.CrossRefPubMedGoogle Scholar
  15. 15.
    Hofman MS, Violet J, Hicks RJ, et al. (177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19(6):825–33.CrossRefPubMedGoogle Scholar
  16. 16.
    Kratochwil C, Giesel FL, Eder M, et al. (1)(7)(7)Lu]Lutetium-labelled PSMA ligand-induced remission in a patient with metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(6):987–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Ahmadzadehfar H, Eppard E, Kurpig S, et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget. 2016;7(11):12477–88.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ahmadzadehfar H, Rahbar K, Kurpig S, et al. Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study. Ejnmmi Res. 2015;5(1):114.PubMedGoogle Scholar
  19. 19.
    Ahmadzadehfar H, Wegen S, Yordanova A, et al. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [(177)Lu]Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2017;44(9):1448–54.CrossRefPubMedGoogle Scholar
  20. 20.
    Baum RP, Kulkarni HR, Schuchardt C, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57(7):1006–13.CrossRefPubMedGoogle Scholar
  21. 21.
    Brauer A, Grubert LS, Roll W, et al. (177)Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44(10):1663–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Kratochwil C, Giesel FL, Stefanova M, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med. 2016;57(8):1170–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Rahbar K, Bode A, Weckesser M, et al. Radioligand therapy with 177Lu-PSMA-617 as A novel therapeutic option in patients with metastatic castration resistant prostate cancer. Clin Nucl Med. 2016;41(7):522–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Rahbar K, Schmidt M, Heinzel A, et al. Response and tolerability of a single dose of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: a multicenter retrospective analysis. J Nucl Med. 2016;57(9):1334–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Yadav MP, Ballal S, Tripathi M, et al. (177)Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment. Eur J Nucl Med Mol Imaging. 2017;44(1):81–91.CrossRefPubMedGoogle Scholar
  26. 26.
    Zechmann CM, Afshar-Oromieh A, Armor T, et al. Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014;41(7):1280–92.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Calopedos RJS, Chalasani V, Asher R, Emmett L, Woo HH. Lutetium-177-labelled anti-prostate-specific membrane antigen antibody and ligands for the treatment of metastatic castrate-resistant prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2017;20(3):352–60.CrossRefPubMedGoogle Scholar
  28. 28.
    Scarpa L, Buxbaum S, Kendler D, et al. The (68)Ga/(177)Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates. Eur J Nucl Med Mol Imaging. 2017;44(5):788–800.CrossRefPubMedGoogle Scholar
  29. 29.
    Ferdinandus J, Eppard E, Gaertner FC, et al. Predictors of response to radioligand therapy of metastatic castrate-resistant prostate cancer with 177Lu-PSMA-617. J Nucl Med. 2017;58(2):312–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of UrologyMedical University of InnsbruckInnsbruckAustria

Personalised recommendations