Repurposing prescription drugs for advanced PC

I posted on another site a series on prescription drugs that may find new uses for advanced prostate cancer. Ever wonder if you might be better off adding metformin? statins? Sprycel? Celebrex? Well, you'll still be wondering after you read it, but you'll probably be in a better position to open a discussion with your oncologist.

Read the preface to the "Introduction" thread first, if you are interested.

advancedpcatalk.freeforums.net/board/1/pcafs-main-discussion-board

Post Edited (Tall Allen) : 8/1/2014 1:27:28 AM (GMT-6)

Thank you, Allen, for posting this.
I had heard of metformin, statins, Celebrex and chloroquine and maybe other related malaria meds. The rest is mostly new to me.
Wonder how many physicians have knowledge or interest in these.

Lam has me on metformin.

One of my many lab tests came out bad on the kidney test. I had to stop the metformin. Kidney function returned to very good. I resumed metformin and just got test results back last week, after being back on metformin for 6 weeks. Kidney and liver functions were fine.

So, there are many drugs that are showing promise, but keep in mind every drug had potential for SE. As we take more and more drugs, there are also interaction dangers. So I would advise getting frequent (every 2 months) tests, just to be on the safe side.

Mel

Thanks Allen for this. Great potential for discussion.

My father showed a response on Celebrex (during the OFF phase, between the two hormone supression cycles, perhaps that is why the OFF phase lasted 2 yrs), but his PC samples were analyzed and found to have a COX-2 receptor. Some trials were done on Celebrex and PC patients were Celebrex failed to halt PC progression in advanced patients, however, I believe if they had only selected ones with a COX-2 receptor, it would have been a different story. Oh, and we just did this on our own, his doctor did not show interest in participating and dismissed Celebrex completely. Since he is a thin man, no cholesterol-lipids-heart issues, I deemed it safe that he takes Celebrex, and he had no side-effects.

Edit: And a question, why do immunosupressants work against cancer? Seems paradoxical.

hi Jerry, just found that rapamune may have an antitumor effect due to prevention of neovascularization or formation of the microvascular network, which is apparently different than angiogenesis. Much medication that works against angiogenesis (e.g. Avastin) has not proven effective in PC.

Checking his patients immune bloodwork -wow -seems like some far-future medical care. Who knows what else that man has up his sleeve....

SpecialLady-
I'm very impressed that you had his cancer checked for COX-2 receptors. Often, there are subsets of patients who do well with some investigational agent, even though it may not work for the population as a whole. Sadly, the pharmaceutical companies often withdraw support for the drug at that point, so we never get to learn about the subsets. For some pharmaceuticals like Celebrex, metformin and statins, they are reasonably safe and cheap, so there is probably no harm and potentially a benefit in trying them.

You asked, "And a question, why do immunosupressants work against cancer? Seems paradoxical."

The quick, and very incomplete answer, is that T cells have both immune helper and suppressor roles. They occur both simultaneously and progressively, and on the same cell. So it can be like a double negative - a T cell may suppress its own immune function that might otherwise enable it to attack the cancer. To add to the complexity, one T cell may attack another T cell. And because the adaptive immune system may eventually adapt to the presence of a non-self antigen, suppressing that function may lead to continued fight against a cancer. Ipilimumab (Yervoy) is a CTLA-4 blocker. CTLA-4 is a protein on the surface of T cells that suppresses its immune function. The most promising (imho) investigational "checkpoint blockers" are antibodies to PD1 and PDL-1, which are proteins on the surface of the cancer cells that turn off the host's immune response (another double negative).

Provenge is an immune stimulant that eventually stops working because of the adaptive immune system. There are trials now where it is combined with immune blockers like Yervoy to see if it can work longer. Immune stimulants and inhibitors have to be used very cautiously because of the possibility of runaway autoimmune reactions.

As Jerry L found, mTOR inhibitors that interrupt the cell survival pathway of cancer cells are coincidentally powerful immunosupressants. They suppress the immune system via cell-cycle arrest on the T cells. The rash was probably an autoimmune reaction. We want our immune systems to work well, but not too well.

Hi Allen, thanks for the explanation. Interesting stuff. If someday we can have measurement points, and see how immune system is behaving and developing over time, perhaps we´ll be able to simply "help" the immune system before it gets outsmarted by the mutations in the cancer cell. I am sure that that first immune response to the developing cancer is a great one, but then it loses advantage. Yervoy gave us new hope in this field.

As for my father, I sent his biopsy specimen to dr.Bonkhoff in Berlin, Germany, and he tested it (histological stains) for 5 different receptors. So my dad´s result were the following (+3 was highest expression):
AR: +2
Cox-2: +2
Somatostatin Receptor: negative
VEGF-R: negative
Chromogranin A: negative

Dr. Bonkhoff suggested using Celebrex in his particular case, but of course saying only it MAY slow down the cancer, not that it will. From our experience (PSA DT), it helped.

SpecialLady,

Your comments inspired me to put together a new section on repurposing existing immunotherapies.

Drug Repurposing for Advanced PC 12. Immunotherapies

I know that Dr.Myers sometimes prescribes Leukine, but I don't know in what context. It will be interesting if doctors write in and tell us what they are using off label.

- Allen

The key is finding a cooperative doctor who will work with you, rather than just providing standard of care. My friend's partner had a great oncologist for his colon cancer, and we tapped into his oncologist's immunotherapy expertise for my friend's prostate cancer. I came in loaded with the studies I posted on the PCAF website, and it piqued his interest, even though prostate cancer is not his specialty. He worked closely with my friend's RO to develop a treatment plan for my friend's oligometastatic (possibly) PC that included a week of Leukine before SBRT to the mets. My friend had to pay out of pocket for the Leukine, which UCLA graciously got for him at cost. He was alerted to be attentive to signs of an immune cascade, and monitored blood levels. I think both doctors welcomed the opportunity to try something new. I've found a lot of doctors, particularly at teaching hospitals, have great intellectual curiosity, and will respond to legitimate evidence.

- Allen

Thanks for sharing, Allen.

Mr. WW was put on Metformin when we questioned its use by others. I suspect the oncologist didn't suggest it on his own, due to not wanting to compound side effects already in force.
So far, there have been no additional side effects.

Anyway, lots of good info!