Aussie Newspaper Report Cautiously Enthusiastic about Lutetium-177 and Patient Progress

[CalBear74]

Here is the link.

afr.com/lifestyle/health/nu...

[pjoshea13]

Michael Hofman is the author of a recent study paper [1].

"17 (57%) of 30 patients (95% CI 37-75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related to [177Lu]-PSMA-617 were grade 1 dry mouth recorded in 26 (87%) patients, grade 1 and 2 transient nausea in 15 (50%), and G1-2 fatigue in 15 (50%). Grade 3 or 4 thrombocytopenia possibly attributed to [177Lu]-PSMA-617 occurred in four (13%) patients. Objective response in nodal or visceral disease was reported in 14 (82%) of 17 patients with measurable disease. Clinically meaningful improvements in pain severity and interference scores were recorded at all timepoints. 11 (37%) patients experienced a ten point or more improvement in global health score by the second cycle of treatment."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/297...

Lancet Oncol. 2018 Jun;19(6):825-833. doi: 10.1016/S1470-2045(18)30198-0. Epub 2018 May 8.

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study.

Hofman MS1, Violet J2, Hicks RJ3, Ferdinandus J4, Thang SP4, Akhurst T3, Iravani A4, Kong G4, Ravi Kumar A4, Murphy DG5, Eu P4, Jackson P4, Scalzo M4, Williams SG2, Sandhu S6.

Author information

1

Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. Electronic address: [e-mail].

2

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

3

Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

4

Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

5

Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

6

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Abstract

BACKGROUND:

Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments.

METHODS:

In this single-arm, single-centre, phase 2 trial, we recruited men (aged 18 years and older) with metastatic castration-resistant prostate cancer and progressive disease after standard treatments, including taxane-based chemotherapy and second-generation anti-androgens, from the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Patients underwent a screening PSMA and FDG-PET/CT to confirm high PSMA-expression. Eligible patients had progressive disease defined by imaging (according to Response Evaluation Criteria In Solid Tumours [RECIST] or bone scan) or new pain in an area of radiographically evident disease, and were required to have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or lower. Eligible patients received up to four cycles of intravenous [177Lu]-PSMA-617, at six weekly intervals. The primary endpoint was PSA response according to Prostate Cancer Clinical Trial Working Group criteria defined as a greater than 50% PSA decline from baseline and toxicity according to CTCAE. Additional primary endpoints were imaging responses (as measured by bone scan, CT, PSMA, and FDG PET/CT) and quality of life (assessed with the EORTC-Q30 and Brief Pain Inventory-Short Form questionnaires), all measured up to 3 months post completion of treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583.

FINDINGS:

Between Aug 26, 2015, and Dec 8, 2016, 43 men were screened to identify 30 patients eligible for treatment. 26 (87%) had received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. The mean administered radioactivity was 7·5 GBq per cycle. 17 (57%) of 30 patients (95% CI 37-75) achieved a PSA decline of 50% or more. There were no treatment-related deaths. The most common toxic effects related to [177Lu]-PSMA-617 were grade 1 dry mouth recorded in 26 (87%) patients, grade 1 and 2 transient nausea in 15 (50%), and G1-2 fatigue in 15 (50%). Grade 3 or 4 thrombocytopenia possibly attributed to [177Lu]-PSMA-617 occurred in four (13%) patients. Objective response in nodal or visceral disease was reported in 14 (82%) of 17 patients with measurable disease. Clinically meaningful improvements in pain severity and interference scores were recorded at all timepoints. 11 (37%) patients experienced a ten point or more improvement in global health score by the second cycle of treatment.

INTERPRETATION:

Our findings show that radionuclide treatment with [177Lu]-PSMA-617 has high response rates, low toxic effects, and reduction of pain in men with metastatic castration-resistant prostate cancer who have progressed after conventional treatments. This evidence supports the need for randomised controlled trials to further assess efficacy compared with current standards of care.

FUNDING:

None.

Copyright © 2018 Elsevier Ltd. All rights reserved.

PMID: 29752180 DOI: 10.1016/S1470-2045(18)30198-0

[Hazard]

I want it now!! But MO (at Peter Mac) says that I am ineligible for Lu-177 trial untill I fail Enzalutamide. FFS, I have finished 9 rounds of chemo and PSA down 90% we should be kicking it in the guts while it's down but no, we have to wait until it goes up again and spreads a bit more. Sometimes you hope that some simple common sense would prevail.

[andrew61]

I have had my first cycle of Lu177 & the 2nd one will be in a few weeks. I am a good candidate for this with PCa limited to lymph nodes & prostate. I'm hoping to fall into the 5% that end up with no visible disease. Then its "just" a matter of finding a way to stop it recurring.

Maybe good diet, supplements, metformin and Clioquinol (see link)

ncbi.nlm.nih.gov/pubmed/278...

[CalBear74 in reply to andrew61]

Preventing recurrence: consider reading Dr. AKM Shamsuddin's text (he is at Univ. of MD Medical School doing cancer research) "Inositol Hexaphosphate & Inositol..." (Amazon) and Dr. Vaclav Vetvicka's, (Univ. of Louisville Medical School, 3rd edition) book about the natural immunomodulator "Beta glucan: Nature's Secret". Both books lead to natural supplements sold over the counter compatible with traditional oncology treatments.

[andrew61 in reply to CalBear74]

Thanks - I do take IP6 & Beta Glucan.

[CalBear74 in reply to andrew61]

What is your daily dose of IP6? As you may know, Dr. Shamsuddin emphasizes dose dependency in gaining positive results.

You are making the right moves!