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Article: A Systematic Review of the Effectiveness and Toxicities of Lutetium-177-labeled PSMA-targeted Radioligand Therapy >>>

GregHouston profile image
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June 4, 2021

In this UroToday Journal Club, Christopher Wallis and Zachary Klaassen highlight a systematic review and meta-analysis examining the effectiveness and toxicities of lutetium-177-labeled prostate-specific membrane antigen-targeted radioligand therapy in metastatic castration-resistant prostate cancer, an article published in European Urology. Drs. Wallis and Klaassen detail the analysis, objective, and findings. 250 studies were reviewed, and 24 studies with 1192 patients were included in the analysis. Prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) with small-molecule, urea-based agents labeled with the β-particle-emitting radionuclide lutetium-177 (177Lu) is a promising new approach. The objective was to perform a comprehensive systematic review and meta-analysis, including the assessment of the effectiveness of lutetium-PSMA, theranostic therapy, the toxicity and severity of toxicity associated with this, as well as to perform a meta-regression, to assess covariate contributions to observed heterogeneity and results between studies. The relatively high number of PSA responders alongside the low rate of severe toxicity indicates the potential promising role of PSMA radioligand therapy in treating men with CRPC.

View the video and read the transcription here>>urotoday.com/video-lectures...

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cesces profile image
cesces

Interesting:

"Advanced prostate cancer is a common cause of cancer death among older men, and prior to death, nearly all patients will develop castration-resistant disease. "

This seems not right to me:

"We will focus on the grade 3 and 4 toxicity in the middle of the screen here, and you can see there are several toxicities listed. Most commonly was anemia, at 8%, diarrhea, 1%, elevated ALT, 2%, elevated AST, 1%, fatigue, 1%, leukopenia, 4%, nausea, 1%, nephropathy, 1%, thrombocytopenia, 4%, and xerostomia, 2%. "

These treatments to my understanding are limited to 8 in number because of the side effects. Specifically damage to salivary glands and kidneys.

Yet those two hardly show up on the list.

One of the things I have observed is an apparent bias, or inefficiency, in collecting side effect data, generally in healthcare.

It is never over counted. And is inherently undercounted. Presumably there must be studies on this undercounting in general, but it seems in general no one places enough emphasis on this.

For instance, a 15 percent reduction in renal function is real, and will result in earlier need for dialysis. But given typically erratic lab readings, might not be noticed or reported.

That just makes me dubious about the quality of results from such a meta study.

For example, I had side effects from Covid vaccine. I didn't bother reporting them. Most people probably didn't.

In the past I have tried reporting problems with a medication. No one wanted to hear it. I am certain that data never got captured.

Certainly the manufacturer had no economic interest in collecting this data as opposed to efficacy data, do they.

In fact they lobby and litigate to avoid black box notices.

So color me dubious about the inherent reliability about the quality of the side effect data in such a meta study.

Ps: I also feel the same generally about pain studies. Never once in my experience have I ever been administered properly a 1 to 10 pain test. Not once. I can't be a one off anomaly.

Spyder54 profile image
Spyder54 in reply tocesces

Cesces,Agreed. Yet we want these drugs FDA appvd so that they can be used for those men where effective. Diff strokes for diff folks. We all present and respond differently. I hv seen multiple posts on Xtandi failure in first 3 months. I was one of them. Switch to Zytiga/Pred and resumption of Psa decline with less side effects. Yet for many here Xtandi has been a game changer and held them at undetectable for multiple years.

Mike

cesces profile image
cesces in reply toSpyder54

"Yet we want these drugs FDA appvd so that they can be used for those men where effective. "

They are approved.

But no one benefits from underreported side effects other than the manufacturer.

Spyder54 profile image
Spyder54 in reply tocesces

Agreed again. If the FDA panel sees a long list of negative SE’s, unlikely to advance a Phase I,II,III Trial, so once approved, you see very few neg side effects. Yet, in the end result we need these approved for where the shoe fits well. We, here, on this site can be honest with our true SE’s and others can make up their minds. Capice’?

cesces profile image
cesces in reply toSpyder54

I think you're not getting it.

The bliss you get from ignorance can kill.

That was basically the excuse for not doing early psa testing.

So I must disagree.

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