Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Nuclear Medicine and Molecular Imaging
Published in: Nuclear Medicine and Molecular Imaging 6/2019

01-12-2019 | Prostate Cancer | Original Article

Safety Profile and Therapeutic Efficacy of One Cycle of Lu177-PSMA in End-Stage Metastatic Castration-Resistant Prostate Cancer Patients with Low Performance Status

Authors: Manoj Gupta, Partha Sarathi Choudhury, Sudhir Rawal, G. Karthikeyan, Vineet Talwar, Kumar Deep Dutta, Amitabh Singh

Published in: Nuclear Medicine and Molecular Imaging | Issue 6/2019

Login to get access

Abstract

Purpose

The aim of this study was to evaluate safety and therapeutic efficacy of lutetium 177 prostate-specific membrane antigen (Lu-177-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with low performance status.

Methods

Twenty-two patients already treated with anti-androgens and docetaxel were enrolled for one cycle of Lu-177-PSMA therapy. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8 weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis.

Results

Partial response (PR), stable disease (SD) and progressive disease (PD) for PSA were seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients respectively treated with mean 6.88 GBq dose of Lu-177-PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistical significant (P < 0.05) difference in pre and post treatment ECOG, VAS, and AQS scores. The ANOVA test showed statistically significant difference in mean doses of Lu-177-PSMA used in three PSA response groups while difference was non-significant for other variables.

Conclusion

We concluded that Lu-177-PSMA therapy has adequate pain palliation in end-stage mCRPC patients with low performance status and it has a potential to become effective therapeutic option in properly selected patients.
Appendix
Available only for authorised users
Literature
1.
Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends--an update. Cancer Epidemiol Biomark Prev. 2016;25:16–27.CrossRef
2.
Jain S, Saxena S, Kumar A. Epidemiology of prostate cancer in India. Meta Gene. 2014;2:596–605.CrossRef
3.
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRef
4.
Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152–60.CrossRef
5.
Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.CrossRef
6.
de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–54.CrossRef
7.
Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.CrossRef
8.
Benešová M, Schäfer M, Bauder-Wüst U, Afshar-Oromieh A, Kratochwil C, Mier W, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med. 2015;56:914–20.CrossRef
9.
Kratochwil C, Giesel FL, Stefanova M, Benešová M, Bronzel M, Afshar-Oromieh A, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med. 2016;57:1170–6.CrossRef
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;3:81–5.PubMed
11.
Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52:637–40.CrossRef
12.
Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Investig New Drugs. 1992;10:239–53.CrossRef
13.
Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol. 2016;34:1402–18.CrossRef
14.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.CrossRef
15.
Basch E, Trentacosti AM, Burke LB, Kwitkowski V, Kane RC, Autio KA, et al. Pain palliation measurement in cancer clinical trials: the US Food and Drug Administration perspective. Cancer. 2014;120:761–7.CrossRef
16.
Jadvar H. Molecular imaging of prostate cancer: PET radiotracers. AJR Am J Roentgenol. 2012;199:278–91.CrossRef
17.
Virgolini I, Decristoforo C, Haug A, Fanti S, Uprimny C. Current status of theranostics in prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:471–95.CrossRef
18.
Mease RC, Foss CA, Pomper MG. PET imaging in prostate cancer: focus on prostate specific membrane antigen. Curr Top Med Chem. 2013;13:951–62.CrossRef
19.
Barinka C, Rojas C, Slusher B, Pomper M. Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer. Curr Med Chem. 2012;19:856–70.CrossRef
20.
Yao V, Parwani A, Maier C, Heston WD, Bacich DJ. Moderate expression of prostate-specific membrane antigen, a tissue differentiation antigen and folate hydrolase, facilitates prostate carcinogenesis. Cancer Res. 2008;68:9070–7.CrossRef
21.
Tagawa ST, Milowsky MI, Morris M, Vallabhajosula S, Christos P, Akhtar NH, et al. Phase II study of lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer. Clin Cancer Res. 2013;19:5182–91.CrossRef
22.
Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40:486–95.CrossRef
23.
Han S, Woo S, Kim YJ, Suh CH. Impact of 68Ga-PSMA PET on the management of patients with prostate cancer: a systematic review and meta-analysis. Eur Urol. 2018;74:179–90.CrossRef
24.
Kabasakal L, AbuQbeitah M, Aygün A, Yeyin N, Ocak M, Demirci E, 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;42:1976–83.CrossRef
25.
Delker A, Fendler WP, Kratochwil C, Brunegraf A, Gosewisch A, Gildehaus FJ, et al. Dosimetry for 177Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:42–51.CrossRef
26.
Ahmadzadehfar H, Rahbar K, Kürpig S, Bögemann M, Claesener M, Eppard E, 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;5:114.PubMed
27.
Rahbar K, Schmidt M, Heinzel A, Eppard E, Bode A, Yordanova 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;57:1334–8.CrossRef
28.
Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schafers M, Essler M, et al. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. J Nucl Med. 2017;58:85–90.CrossRef
29.
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;20:352–60.CrossRef
30.
Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [177Lu]-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;19:825–33.CrossRef
31.
Meller B, Bremmer F, Sahlmann C, Hijazi S, Bouter C, Trojan L, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5:66.CrossRef
32.
Murga JD, Moorji SM, Han AQ, Magargal WW, DiPippo VA, Olson WC. Synergistic co-targeting of prostate-specific membrane antigen and androgen receptor in prostate cancer. Prostate. 2015;75:242–54.CrossRef
33.
Vallabhajosula S, Jhanwar Y, Tagawa S, Epstein J, Babich J, Youn T, et al. 99mTc-MIP-1404 Planar and SPECT scan: Imaging biomarker of androgen receptor (AR) signaling and prostate specific membrane antigen (PSMA) expression. J Nucl Med. 2016;57(supplement 2):1541.
Metadata
Title
Safety Profile and Therapeutic Efficacy of One Cycle of Lu177-PSMA in End-Stage Metastatic Castration-Resistant Prostate Cancer Patients with Low Performance Status
Authors
Manoj Gupta
Partha Sarathi Choudhury
Sudhir Rawal
G. Karthikeyan
Vineet Talwar
Kumar Deep Dutta
Amitabh Singh
Publication date
01-12-2019
Publisher
Springer Singapore
Published in
Nuclear Medicine and Molecular Imaging / Issue 6/2019
Print ISSN: 1869-3474
Electronic ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-019-00624-8

Other articles of this Issue 6/2019

Nuclear Medicine and Molecular Imaging 6/2019 Go to the issue

Interesting image

Orbital IgG4 Disease: Imaging Findings on 68Ga-DOTANOC PET/CT

Perspective

Perspectives in TSPO PET Imaging for Neurologic Diseases

Original Article

Prognostic Value of Metabolic Information in Advanced Gastric Cancer Using Preoperative 18F-FDG PET/CT

Original Article

Reverse Warburg Effect-Related Mitochondrial Activity and 18F-FDG Uptake in Invasive Ductal Carcinoma

Original Article

Effect of ME Collimator Characteristic, Energy Window Width, and Reconstruction Algorithm Selection on Imaging Performance of Yttrium-90: Simulation Study

Review

Radioembolization for the Treatment of Primary and Metastatic Liver Cancers