Metastatic Castration Resistant Prostate Cancer (mCRPC)

Posted by bryane @bryane, Aug 21 5:25pm

Has anyone had experience with Actinium - 225 which is an alpha based radiological treatment. I believe only Germany has incorporated Actinium 225 treatment as part of regular clinical practice.

Interested in more discussions like this? Go to the Prostate Cancer Support Group.

jeff Marchi | @jeffmarc | Aug 23 10:54am

In reply to @johnernest "I found this information: Here’s what I found regarding the combination of doxorubicin (a chemotherapy agent)..." + (show)

@johnernest

I found this information:
Here’s what I found regarding the combination of doxorubicin (a chemotherapy agent) and Viagra (sildenafil) in the treatment of prostate cancer:
Scientific Basis & Preclinical Findings
1. Enhanced Cancer Cell Killing & Cardiac Protection
Lab studies and mouse models have shown that sildenafil (a PDE-5 inhibitor) enhances the effectiveness of doxorubicin against prostate cancer cells. This combo:
Boosts apoptosis (cell death) in PC-3 and DU145 cancer cells.
In mouse models, the combination significantly reduced tumor size while also protecting against the heart damage doxorubicin typically causes.
2. Mechanistic Insight—DNA Repair Disruption
Further research showed that sildenafil impairs the cellular DNA repair systems (both homologous recombination and non-homologous end joining). This makes doxorubicin-induced DNA damage more lethal to cancer cells.
3. CD95-Mediated Apoptosis
Another pathway involves modulation of CD95 (Fas receptor) and its inhibitor FLIP. Sildenafil plus doxorubicin reduces FLIP levels, enabling CD95 to drive more potent apoptosis in prostate cancer cells.
Clinical Evidence & Early Human Data
There is very limited human clinical trial data for this combination, but one randomized study did explore it:
Safety vs. Efficacy: In a clinical study examining doxorubicin with and without sildenafil, the combination was generally tolerated with mostly mild side effects (e.g., headache, flushing). However, a concerning decline in left ventricular ejection fraction (LVEF) occurred in one patient—but that individual was also on trastuzumab, making it unclear whether sildenafil was responsible. Ultimately, the trial continued, but found no evidence of cardiac protection from adding sildenafil.
Summary:
“There’s promising preclinical evidence showing that sildenafil can enhance doxorubicin’s cancer-killing effects—by impairing DNA repair pathways and promoting apoptosis—and even toggle some heart protection in animal models. However, in the limited human data available, sildenafil didn’t reduce heart damage and didn’t show treatment benefit. More clinical trials are needed before this combination can be considered for actual use.

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As mentioned by others, This definitely sounds risky. The last Couple of sentences really makes one wonder whether this can work for many of us.

However, in the limited human data available, sildenafil didn’t reduce heart damage and didn’t show treatment benefit. More clinical trials are needed before this combination can be considered for actual use.

Prostate cancer patients usually die of something other than prostate cancer, Heart disease is a big one and this seems to exacerbate the results for anyone with heart issues.

lag | @lag | Aug 24 2:04pm

Clinical trials of Actinium-225 have only recently begun in the U.S. We are eagerly awaiting one to open near us, but there is no word yet on when that might happen. In the meantime, here is an article I found that discusses the start of clinical trials in the U.S. using Actinium produced in a Department of Energy accelerator. This method of production promises to greatly increase the availability of the isotope. The URL for the below article is https://www.energy.gov/science/articles/groundbreaking-cancer-therapy-clinical-trial-us-department-energys-accelerator

Groundbreaking Cancer Therapy Clinical Trial with U.S. Department of Energy’s Accelerator-Produced Actinium-225 Set to Begin this Summer
National laboratories’ accelerator-produced Ac-225 to be used in an FDA-approved targeted cancer therapy clinical trial for the first time

Office of Science

June 18, 2025

2
min
minute read time
The Department of Energy’s (DOE) Isotope Program, within the Office of Science, will supply a U.S. based company with accelerator produced actinium-225 (Ac-225) in support of an upcoming U.S. clinical trial for cancer therapy for the first time. This is a significant milestone in the advancement of radiopharmaceutical development and cancer therapy because it opens a potential new pipeline for this lifesaving isotope.

"We are proud to enable U.S. based companies to push past the boundaries on how we combat cancer in this country," said Christopher Landers, Director of the Office of Isotope R&D and Production. "This collaboration exemplifies the purpose of our mission to ensure that critical isotopes are readily available to meet domestic needs across all aspects of society, including medical therapies."

The clinical trial is scheduled to begin in summer 2025 and will be the first to rely on accelerator-produced Ac-225 for human patient care. Ac-225 is a radioisotope in short supply because of the current complicated production process. The Isotope Program has established a scalable production method to fill this need using the particle accelerators at DOE's Brookhaven National Laboratory and Los Alamos National Laboratory. For many years, researchers have used the accelerator-produced Ac-225 in developing potential cancer treatment options and in animal studies for safety and efficacy. Now, the accelerator-produced Ac-225 will be explored for clinical use.

The Isotope Program produces critical radioactive and stable isotopes in short supply for the nation and is one of a few or only global producers for these novel isotopes. Isotopes are high-priority commodities of strategic importance and are essential in medical diagnosis and treatment, industrial applications in oil and gas, national security, quantum information systems, space exploration and communications, discovery science and various other applications. Isotopes directly enable emerging technology, and contribute to the economic, technical, and scientific strength of the United States.