Prostate Cancer Drug Could Protect Bone Marrow from Damage Caused by Radiation

[JLS1]

Are they talking about Casodex? - and if so, and it's known to be safe, why not try this now?!!:

“Giving the mice a single dose of the LHRH-blocking drug 24 hours after the radiation hit was enough to protect them from its lethal effects,” says Enrico Velardi, a scientist in the van den Brink lab and the first author of the new study.

LHRH is produced by the brain’s hypothalamus and sets in motion a chain of events that leads to the production of sex hormones in the body. The LHRH-blocking drug lowers the levels of an intermediate step in this chain called luteinizing hormone (LH). The scientists discovered that blood stem cells in the bone marrow respond to LH by dividing. Following an insult to the bone marrow, such as radiation exposure, inhibiting LH prevents cells from proliferating thus maintaining them in a more quiescent state. This dormancy protects blood stem cells from radiation damage and allows them to replenish the blood supply after the injury."

mskcc.org/blog/prostate-can...

[pjoshea13]

My bet is Degarelix [Firmagon].

-Patrick

[Tall_Allen]

They write: "Here we found that a luteinizing hormone (LH)-releasing hormone antagonist (LHRH-Ant), currently in wide clinical use for sex-steroid inhibition, promoted hematopoietic recovery and mouse survival when administered 24 h after an otherwise-lethal dose of total-body irradiation (L-TBI)."

The only such medicine in wide clinical use is Firmagon.

nature.com/articles/nm.4470

Based on that, Firmagon may be protective when one is taking Xofigo.

[JLS1 in reply to Tall_Allen]

I wonder how long after the xofigo treatment is too late for the benefit?

My husband ended up in the ER on Friday afternoon, per MO's direction (per extreme weakness symptoms we were reporting), due to severe anemia. This is 2 weeks after his last, 4th, Xofigo injection, so it's not too surprising.

His hemoglobin was 6.1! Platelets were at 53,000 (not low enough to get platelets). So they gave him a total of 3 transfusions (3 units) over the next 24 hours. Here are the results:

After 1st infusion: 6.7 - platelets @ 52,000

After 2nd infusion: 7.8 - platelets @ 57,000

After 3rd infusion: 8.4 - platelets @ 51,000

MO is concerned and wants to delay next Xofigo injection which was scheduled for Jan 7th.

[Tall_Allen in reply to JLS1]

Well, according to that mouse study, "when administered 24 h after an otherwise-lethal dose of total-body irradiation (L-TBI)." It's a study in mice and human physiology is different, but there is no harm in switching him from Lupron to Firmagon, so why not try it?

[GeorgeGlass in reply to JLS1]

what is Xofigo used for?

[JLS1 in reply to GeorgeGlass]

Xofigo is radium 223 given by injection for bone mets

[AlanMeyer]

Yes indeed, Patrick and Allen got the drug right. The drug they tested is Firmagon/degarelix, as described in what appears to be the scientific publication supporting the press release:

ncbi.nlm.nih.gov/pubmed/293...

[tango65]

They used Firmagon (degarelix).:

"Inhibition of sex steroids, which can be achieved pharmacologically in a reversible fashion, is a well-described strategy for promoting lymphopoiesis in the BM and thymus 6,7,10,11. Although the most common clinical method of sex-steroid ablation has been through use of LHRH agonists, we have previously proposed that use of LHRH antagonists may be a more rational approach to achieve immediate sex-steroid ablation for immune regeneration, for two reasons: LHRH antagonism is more rapid than agonism, and antagonism abrogates the initial surge in sex steroids caused by agonism . On the basis of these findings, together with previous evidence of the effects of sex-steroid inhibition on HSC function and the rapid hormonal suppression mediated by LHRH antagonism, we hypothesized that an LHRH antagonist, when administered after hematopoietic insult, might provide a rational noncellular medical countermeasure for mitigating radiation injury and promoting hematopoietic regeneration.

To test this hypothesis, we administered to male mice an L-TBI dose of 840 cGy, which resulted in lethality in more than 90% of the mice (Supplementary Fig. 1a). Mice receiving the LHRH-Ant (degarelix), compared with control mice treated with vehicle alone, showed significantly greater survival 24 h after L-TBI exposure (Fig. 1a)."

ncbi.nlm.nih.gov/pmc/articl...

[cesanon]

"The only such medicine in wide clinical use is Firmagon." Tall Allen

Anyone have any idea why they would not just come out and name the drug they are talking about? They must have their own good reasons, but why are they being so obtuse?

[MateoBeach]

Yes Firmagon seems most likely. If indeed the mechanism is by having little or no LH activity during/after the radiation, then anyone on ADT when undergoing RT would already be covered in that respect.