Sirolimus is a pricey drug used by transplant patients to prevent rejection, but also used by some now, including some members here, as a “life extension” drug. When I recently tried to refill my script, the insurance company, BCBS Medicare advantage, indicated they would not cover Sirolimus if it is prescribed off label.
Does anyone have a source that is reasonably priced?
Very dangerous - it has been proved ineffective for PCa.
I have been on sirolimus since my heart transplant in 2005. Right now I am 2 years with ADT and don’t seem to have any effects. Except for some shortness of breath, I still feel like I’m still in great shape for 86 years.
With Rapamycin being dangerous, do you mean its impact on neutrophils?
With R being ineffective for PCa, are you referring to work by Ruggero at UCSF around 2012?
For example:
"52% of enrolled patients had serious adverse events...Temsirolimus monotherapy has minimal activity in chemotherapy-naïve CRPC."
ncbi.nlm.nih.gov/pmc/articl...
"Everolimus demonstrated predictable toxicity in advanced and heavily pretreated patients with mCRPC. No clinical or clear pathologic effects despite downstream TORC1 target inhibition, suggesting that single agent everolimus has no clinical utility in men with mCRPC."
sciencedirect.com/science/a...
Sirolimus (and other mTOR inhibitors):
Serious Reactions:
immunosuppression
malignancy
lymphoma
infection, severe
opportunistic infection
PML
nephropathy, BK virus-assoc.
nephrotic syndrome
hemolytic uremic syndrome
TTP
thrombotic microangiopathy
venous thromboembolism
myelosuppression
hypersensitivity rxn
anaphylaxis
anaphylactoid rxn
angioedema
exfoliative dermatitis
impaired wound healing
lymphocele
ascites
pericardial effusion
pleural effusion
interstitial lung dz
hepatotoxicity
hypokalemia
osteonecrosis
infertility
Common Reactions:
peripheral edema
hyperlipidemia
HTN
Cr incr.
constipation
pain
diarrhea
headache
fever
infection
anemia
nausea
arthralgia
thrombocytopenia
acne
dizziness
myalgia
diabetes mellitus
rash
proteinuria
tachycardia
stomatitis
leukopenia
abnormal healing
LDH incr.
hypokalemia
epistaxis
pyelonephritis
ovarian cysts
menstrual disorder
photosensitivity
That’s an apples and oranges comparison. I never said that I had taken Sirolimus to treat PCa. I took it as a general “life extension” drug - same concept as healthy people taking deprenyl. There is a fair amount of evidence that it may have some value in that regard, as it was my naturopathic inclined PCP who suggested it.
More importantly, the side effects you mention are from a dosage of 10 mg/day. The common life extension dosage is 4 mg once per week in two month cycles with a month off between.
Why are you posting on an APC forum? It's an high-adverse effect drug at doses normally prescribed. If you want to risk your life taking it - that's your decision - but why post it here?
There is no clinical evidence that it is worth the risk.
Low dose Sirolimus/Rapamycin has been posted about on here multiple times in the last six years, so forgive me for not knowing the posting rules and for not knowing that you had been appointed as the content police. I asked a simple question, and you posted an unresponsive, negative comment. If I didn’t know better, I would think you don’t like me. Oh, sorry again, I do know better.
I don't know you and have no personal opinion. I think we all have a responsibility to not harm others.
I was not aware of those studies showing lack of efficacy of rapamycin on advanced and heavily pre-treated mCRPC; I appreciate learning this.
As I started looking, I found an explanation of why the promising animal studies on PCa - this is not rare! - had not translated to humans:
From urology.ucsf.edu/news/all/2...
"When he examined the effect of rapamycin and rapamycin-like drugs in prostate cancer cells, Ruggero and his team found that these drugs do not fully block mTOR activity. In addition, both the Ruggero and Febbo laboratories have found that an oncogene called MYC, which is frequently expressed at high levels in prostate cancer, can limit inhibition of mTOR and prostate cancer’s sensitivity to rapamycin".
If the oncogene MYC limits mTor inhibition in the case of prostate cancer, both anti-cancer and anti-aging effect could be inhibited which is interesting for someone like me with an interest in both.
My (false?) hope is that in a case like my own with mHSPC that is dormant/senescent since one year, the MYC will not be prominent so the anti-cancer and anti-aging effects will not be nullified.
You are right that animal studies almost always do not translate to humans, and should be ignored by patients.
You mean except for studies such as:
ascopubs.org/doi/abs/10.120...
Many others, re Rapa & many different cancers, like this March, 2023 study:
nature.com/articles/s41467-...
And 20 years of use, show Rapa is not dangerous.
Did you read what you posted? The first was a dose finding study:
"There was no significant change in PSA level" but 2/8 dropped out and ⅛ had serious neutropenia.
The second link was just a useless lab study.
There have been several clinical trials with mTor inhibitors. In this one of everolimus:"Fourteen patients (54%) developed Grade 3 (13 patients) or Grade 4 (1 patient with sepsis) adverse events attributable to treatment." while PSA response was moderate (63% had a PSA response >50%)
ncbi.nlm.nih.gov/pmc/articl...
In this trial, of everolimus (RAD001) only 2 of 36 patients had a PSA response>50%
bjui-journals.onlinelibrary...
It appears to be ineffective at doses that are safe, but at doses that are effective, it is unsafe.
There have been attempts to reduce the dose and its toxicity by combining in a cocktail with chemo and other agents. In this combination therapy, "Our results do not support the hypothesis that this combination of agents improves upon the results obtained with docetaxel monotherapy in an unselected population of chemotherapy-naive patients with CRPC."
You could try Tailormade Compounding. Contact them and ask if they have a prescribing physician that could do a virtual consult to discuss it
I too am taking Rapamycin for anti-aging, with the hope that PCa would be attacked too; I just posted TA on the latter.
He showed a long list of side-effects. I have been struck by two, that I know of.
When taking about 6 mg of Rapamycin every two weeks, my neutrophils get knocked down by 60%. Reducing the dose to around 3 mg, they only get reduced slightly. No effect on other white blood cells, or RBC. And I get rashes, unbearable if untreated but rapidly eliminated with an anti-inflammatory cream. They became less frequent when I went from a weekly to biweekly regimen.
I now take 1 mg of R biweekly, together with two freshly squeezed grapefruits which roughly treble absorption. Canned juice won´t do it, it lacks a needed enzyme. Similar to you, 8 weeks on, 5 weeks off to reduce risk of up-regulation of mTOR.
The possible limits to mTOR inhibition from Rapamycin in the link I posted TA, along with his links to lack of efficacy on cancer, is a concern. I am not sure what to make of it yet. Perhaps the lack of mTOR inhibition does not affect anti-aging.
Last sentence should read: Perhaps the lack of mTOR inhibition re prostate cancer cells does not affect aging.
Confused about treatment options
Need info from the brains for an additional drug Kaiser wants me to add to the heap. 
Metformin.
Chemo
Drug Resistence
