Generic placeholder image

Current Radiopharmaceuticals

Editor-in-Chief

ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

Research Article

177Lu-PSMA-617 Radioligand Treatment in Elderly Patients with Metastatic Castration-resistant Prostate Cancer: Therapeutic Efficacy and Safety Assessment

Author(s): Ertan Sahin*, Umut Elboga, Ufuk Cimen, Merve Okuyan and Yusuf Burak Cayirli

Volume 17, Issue 4, 2024

Published on: 03 April, 2024

Page: [356 - 363] Pages: 8

DOI: 10.2174/0118744710284661240328094119

Price: $65

Abstract

Objective: This study aimed to evaluate the therapeutic efficacy and safety of 177Lutetium-Prostate Specific Membrane Antigen (177Lu-PSMA-617) radioligand treatment (RLT) in metastatic castration-resistant prostate cancer (mCRPC) patients with aged older than 75 years.

Methods: A total of 37 patients with mCRPC aged older than 75 years treated with 177Lu- PSMA-617 were included in this study.

Pre-therapy and post-therapy biochemical, metabolic, and clinical response results and Hb, TLC, platelet, serum creatinine and bilirubin levels were checked to evaluate the therapeutic efficacy and toxicity profile. The Common Terminology Criteria for Adverse Events was used for grading adverse events caused by 177Lu-PSMA-617 treatment.

Results: The mean age of the patients included in the study was 79.8±2.9 (76-92). The number of 177Lu-PSMA-617 treatment cycles ranged from two to four, and the mean administered radioactivity dose was 5.6±0.8 GBq per cycle. Partial biochemical response (PR) and partial metabolic response (PMR) were observed in 11 (29.7%) and 15 (40.6%) patients after treatment, respectively. Although improvement in ECOG scores was observed in 5 (13.5%) patients after treatment, it was not statistically significant. Grade 2 and 3 Hb toxicity was observed in 10 (27%) and 2 (5.4%) patients, respectively. Grade 2 leukocytopenia in six patients, Grade 1 thrombocytopenia in six patients, and Grade 2 serum creatinine toxicity in five patients were seen after the treatment. On the other hand, no patients developed liver toxicity and grade 3 or 4 leukocytopenia, thrombocytopenia or creatinine toxicity.

Conclusion: 177Lu-PSMA-617 treatment was a safe and effective treatment option for properly selected elderly mCRPC patients.

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Halabi, S.; Vogelzang, N.J.; Kornblith, A.B.; Ou, S.S.; Kantoff, P.W.; Dawson, N.A.; Small, E.J. Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J. Clin. Oncol., 2008, 26(15), 2544-2549.
[http://dx.doi.org/10.1200/JCO.2007.15.0367] [PMID: 18487572]
[3]
Pomper, M.G.; Musachio, J.L.; Zhang, J.; Scheffel, U.; Zhou, Y.; Hilton, J.; Maini, A.; Dannals, R.F.; Wong, D.F.; Kozikowski, A.P. 11C-MCG: Synthesis, uptake selectivity, and primate PET of a probe for glutamate carboxypeptidase II (NAALADase). Mol. Imaging, 2002, 1(2), 96-101.
[http://dx.doi.org/10.1162/153535002320162750] [PMID: 12920850]
[4]
Leibowitz, R.; Davidson, T.; Gadot, M.; Aharon, M.; Malki, A.; Levartovsky, M.; Oedegaard, C.; Saad, A.; Sandler, I.; Ben-Haim, S.; Domachevsky, L.; Berger, R. A retrospective analysis of the safety and activity of lutetium‐177‐prostate‐specific membrane antigen radionuclide treatment in older patients with metastatic castration‐resistant prostate cancer. Oncologist, 2020, 25(9), 787-792.
[http://dx.doi.org/10.1634/theoncologist.2020-0100] [PMID: 32430954]
[5]
Violet, J.; Sandhu, S.; Iravani, A.; Ferdinandus, J.; Thang, S.P.; Kong, G.; Kumar, A.R.; Akhurst, T.; Pattison, D.; Beaulieu, A.; Mooi, J.; Tran, B.; Guo, C.; Kalff, V.; Murphy, D.G.; Jackson, P.; Eu, P.; Scalzo, M.; Williams, S.; Hicks, R.J.; Hofman, M.S. Long-term follow-up and outcomes of retreatment in an expanded 50-patient single-center phase II prospective trial of 177Lu-PSMA-617 theranostics in metastatic castration-resistant prostate cancer. J. Nucl. Med., 2020, 61(6), 857-865.
[http://dx.doi.org/10.2967/jnumed.119.236414] [PMID: 31732676]
[6]
Weineisen, M.; Schottelius, M.; Simecek, J.; Baum, R.P.; Yildiz, A.; Beykan, S.; Kulkarni, H.R.; Lassmann, M.; Klette, I.; Eiber, M.; Schwaiger, M.; Wester, H.J. 68Ga- and 177Lu-labeled PSMA I&T: Optimization of a PSMA-targeted theranostic concept and first proof-ofconcept human studies. J. Nucl. Med., 2015, 56(8), 1169-1176.
[http://dx.doi.org/10.2967/jnumed.115.158550] [PMID: 26089548]
[7]
Scher, H.I.; Morris, M.J.; Stadler, W.M.; Higano, C.; Basch, E.; Fizazi, K.; Antonarakis, E.S.; Beer, T.M.; Carducci, M.A.; Chi, K.N.; Corn, P.G.; de Bono, J.S.; Dreicer, R.; George, D.J.; Heath, E.I.; Hussain, M.; Kelly, W.K.; Liu, G.; Logothetis, C.; Nanus, D.; Stein, M.N.; Rathkopf, D.E.; Slovin, S.F.; Ryan, C.J.; Sartor, O.; Small, E.J.; Smith, M.R.; Sternberg, C.N.; Taplin, M.E.; Wilding, G.; Nelson, P.S.; Schwartz, L.H.; Halabi, S.; Kantoff, P.W.; Armstrong, A.J. Trial design and objectives for castration-resistant prostate cancer: Updated recommendations from the prostate cancer clinical trials working group 3. J. Clin. Oncol., 2016, 34(12), 1402-1418.
[http://dx.doi.org/10.1200/JCO.2015.64.2702] [PMID: 26903579]
[8]
Young, H.; Baum, R.; Cremerius, U.; Herholz, K.; Hoekstra, O.; Lammertsma, A.A.; Pruim, J.; Price, P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: Review and 1999 EORTC recommendations. Eur. J. Cancer, 1999, 35(13), 1773-1782.
[http://dx.doi.org/10.1016/S0959-8049(99)00229-4] [PMID: 10673991]
[9]
Green, S.; Weiss, G.R. Southwest oncology group standard response criteria, endpoint definitions and toxicity criteria. Invest. New Drugs, 1992, 10(4), 239-253.
[http://dx.doi.org/10.1007/BF00944177] [PMID: 1487397]
[10]
Sartor, O.; de Bono, J.; Chi, K.N.; Fizazi, K.; Herrmann, K.; Rahbar, K.; Tagawa, S.T.; Nordquist, L.T.; Vaishampayan, N.; El-Haddad, G.; Park, C.H.; Beer, T.M.; Armour, A.; Contreras, P.W.J.; DeSilvio, M.; Kpamegan, E.; Gericke, G.; Messmann, R.A.; Morris, M.J.; Krause, B.J. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N. Engl. J. Med., 2021, 385(12), 1091-1103.
[http://dx.doi.org/10.1056/NEJMoa2107322] [PMID: 34161051]
[11]
Khreish, F.; Ghazal, Z.; Marlowe, R.J.; Rosar, F.; Sabet, A.; Maus, S.; Linxweiler, J.; Bartholomä, M.; Ezziddin, S. 177Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostatecancer: Initial 254-patient results from a prospective registry (REALITY Study). Eur. J. Nucl. Med. Mol. Imaging, 2022, 49(3), 1075-1085.
[http://dx.doi.org/10.1007/s00259-021-05525-7] [PMID: 34494131]
[12]
Baum, R.P.; Kulkarni, H.R.; Schuchardt, C.; Singh, A.; Wirtz, M.; Wiessalla, S.; Schottelius, M.; Mueller, D.; Klette, I.; Wester, H.J. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: Safety and efficacy. J. Nucl. Med., 2016, 57(7), 1006-1013.
[http://dx.doi.org/10.2967/jnumed.115.168443] [PMID: 26795286]
[13]
Kesavan, M.; Turner, J.H.; Meyrick, D.; Yeo, S.; Cardaci, G.; Lenzo, N.P. Salvage radiopeptide therapy of advanced castrate-resistant prostate cancer with lutetium-177-labeled prostate-specific membrane antigen: Efficacy and safety in routine practice. Cancer Biother. Radiopharm., 2018, 33(7), 274-281.
[http://dx.doi.org/10.1089/cbr.2017.2403] [PMID: 29989440]
[14]
Yadav, M.P.; Ballal, S.; Bal, C.; Sahoo, R.K.; Damle, N.A.; Tripathi, M.; Seth, A. Efficacy and safety of 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer patients. Clin. Nucl. Med., 2020, 45(1), 19-31.
[http://dx.doi.org/10.1097/RLU.0000000000002833] [PMID: 31789908]
[15]
Gupta, M.; Choudhury, P.S.; Rawal, S.; Karthikeyan, G.; Talwar, V.; Dutta, K.D.; Singh, A. Safety profile and therapeutic efficacy of one cycle of Lu177-PSMA in end-stage metastatic castration-resistant prostate cancer patients with low performance status. Nucl. Med. Mol. Imaging, 2019, 53(6), 423-431.
[http://dx.doi.org/10.1007/s13139-019-00624-8] [PMID: 31867078]
[16]
Assadi, M.; Rezaei, S.; Jafari, E.; Rekabpour, S.J.; Ravanbod, M.; Zohrabi, F.; Amini, A.; Keshmiri, S.; Dadgar, H.; Ahmadzadehfar, H. Potential application of lutetium-177-labeled prostate-specific membrane antigen-617 radioligand therapy for metastatic castration-resistant prostate cancer in a limited resource environment: Initial clinical experience after 2 years. World J. Nucl. Med., 2020, 19(1), 15-20.
[http://dx.doi.org/10.4103/wjnm.WJNM_20_19] [PMID: 32190017]
[17]
Grubmüller, B.; Senn, D.; Kramer, G.; Baltzer, P.; D’Andrea, D.; Grubmüller, K.H.; Mitterhauser, M.; Eidherr, H.; Haug, A.R.; Wadsak, W.; Pfaff, S.; Shariat, S.F.; Hacker, M.; Hartenbach, M. Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer. Eur. J. Nucl. Med. Mol. Imaging, 2019, 46(5), 1063-1072.
[http://dx.doi.org/10.1007/s00259-018-4236-4] [PMID: 30569186]
[18]
Khreish, F.; Wiessner, M.; Rosar, F.; Ghazal, Z.; Sabet, A.; Maus, S.; Linxweiler, J.; Bartholomä, M.; Ezziddin, S. Response assessment and prediction of progression-free survival by 68Ga-PSMA-11 PET/CT based on tumor-to-liver ratio (TLR) in patients with mCRPC undergoing 177Lu-PSMA-617 radioligand therapy. Biomolecules, 2021, 11(8), 1099.
[http://dx.doi.org/10.3390/biom11081099] [PMID: 34439768]
[19]
Kurth, J.; Kretzschmar, J.; Aladwan, H.; Heuschkel, M.; Gummesson, A.; Bergner, C.; Kundt, G.; Hakenberg, O.W.; Krause, B.J.; Schwarzenböck, S.M. Evaluation of [68Ga]Ga-PSMA PET/CT for therapy response assessment of [177Lu]Lu-PSMA radioligand therapy in metastasized castration refractory prostate cancer and correlation with survival. Nucl. Med. Commun., 2021, 42(11), 1217-1226.
[http://dx.doi.org/10.1097/MNM.0000000000001446] [PMID: 34424870]
[20]
Rosar, F.; Wenner, F.; Khreish, F.; Dewes, S.; Wagenpfeil, G.; Hoffmann, M.A.; Schreckenberger, M.; Bartholomä, M.; Ezziddin, S. Early molecular imaging response assessment based on determination of total viable tumor burden in [68Ga]Ga-PSMA-11 PET/CT independently predicts overall survival in [177Lu]Lu-PSMA-617 radioligand therapy. Eur. J. Nucl. Med. Mol. Imaging, 2022, 49(5), 1584-1594.
[http://dx.doi.org/10.1007/s00259-021-05594-8] [PMID: 34725725]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy