LDN study for breast cancer...effective!

Wow, very cool. Cheap and no side effects. Even if it only works for some women it could be a great new treatment to add to the arsenal. I'm confused by this, though: "A dosage of 10-8 M paclitaxel given alone caused marked apoptosis, but resulted in 60% less cell death when given in the presence of OGF. In patients, paclitaxel often is accompanied by side effects that reduce compliance." Do they mean it causes 60% less non-cancerous cells to die? Because if it's reducing apoptosis of cancer cells, that would be undermining treatment. They need to clarify that.

I believe this study was specific to triple-negative breast cancer...

"Human triple-negative breast cancer can be treated by modulation of the opioid growth factor (OGF) - OGFr pathway. OGF suppresses cell growth by 20 percent within 24 hours in a receptor-mediated manner. Blockade of OGFr using low dosages of the opioid antagonist naltrexone causes a compensatory increase in OGF and results in 35 percent reductions in cell number within 72 hours. These data demonstrate a novel biological pathway for treatment of this deadly breast cancer."

http://www.sciencedaily.com/releases/2013/08/130810063639.htm

This sounds promising. If I'm reading it correctly, the study has been done in vitro. Any time line for live clinical trials?

Caryn

I was looking at LDN a few years ago (2011) when my Aunt had stage 4 BC. At the time I ran across a clinical trial being done on full strength Naltrexone (50 mg dosage as opposed to 4.5 mg)  on women with metastatic BC no longer responding to hormonal therapy, but when I checked recently I saw that study had been terminated.  I remember reading at the time that the higher dosage would have negated the effects that are supposed to fight cancer, so I wondered why they were using that dosage. 

It looks like one of those things that have to be fine-tuned.

The goal is to increase endogenous endorphins which allows the immune system "to kill cancer cells faster than they can grow." I'm guessing you could do this to some extent with daily exercise. Chocolate and Vitamin C also release endorphins.

Falleaves, yes, I wonder too why these trials were cancelled. LDN like cannabis has many proponents in the medical field and various applications for potential benefit. 

http://cam.cancer.gov/newsletter/2012-spring/featu...

http://www.ldnscience.org/low-dose-naltrexone/publ...

The reasons the trials were terminated could be many.  One of the purposes of a Phase II clinical trial is to determine appropriate- and effective dosage, and identify countraindications, i.e., the adverse events that emerge that are dose-dependent and/or related to outside factors such as other comorbities or medications.  It could be that the trials simply could not find a balance between dosage and effectiveness, i.e., too high a dose could produce unwanted effects, too low a dose might not have any effect, and the "sweet spot" simply could not be identified; it could be that other medications necessary to the quality-of-life of these patients reduced LDN efficacy or the other way around.  The authors of the article did state that LDN reduced the effect of the opiates needed to make these patients comfortable.  For many, the level of pain that would have to be endured by the patient while testing whether- or not LDN could prove effective in the long run would be unethical.

Unfortunately, "early promise" doesn't always pan out in research and there are a number of reasons.  Substances that look like they could be practise-changing don't always hold up under more intense scrutiny.  Optimal dosing is a delicate business and, perhaps, the researchers simply could not determine what that was.  If other, independent research groups could not duplicate the findings of these early clinical trials, it could be that a major flaw in the original study design emerged that construed a bias in the results and, once that design flaw was corrected and controlled, LDN didn't pan out as hoped.  A substance that looks like it has a great deal of promise in a small, controlled population may not turn out to have as substantial an effect - or any effect - as hoped when exposed to a wider demographic, i.e., LDN's early promise could have been the result of "chance" and not "effect", and that's why the trials were cancelled.

Wow, am I confused. I looked at the abstract for the study that is the basis of this thread, and not once does it mention breast cancer cells, triple negative or otherwise. Are they just extrapolating out that it would be effective for triple neg, since ALL breast cancer cells have this receptor? (In which case, why not say it could be effective for all forms of BC, including triple neg?)

SelenaWolf, you said, "Every article and source I could find on this study all stressed that successful treatment occurred in triple negative patients." Would you mind sharing some of these other articles? 

http://ebm.sagepub.com/content/238/5/579

The opioid growth factor (OGF) – opioid growth factor receptor (OGFr) axis is a biological pathway that is present in human ovarian cancer cells and tissues. OGF, chemically termed [Met⁵]-enkephalin, is an endogenous opioid peptide that interfaces with OGFr to delay cells moving through the cell cycle by upregulation of cyclin-dependent inhibitory kinase pathways. OGF inhibitory activity is dose dependent, receptor mediated, reversible, protein and RNA dependent, but not related to apoptosis or necrosis. The OGF-OGFr axis can be targeted for treatment of human ovarian cancer by (i) administration of exogenous OGF, (ii) genetic manipulation to over-express OGFr and (iii) use of low dosages of naltrexone, an opioid antagonist, which stimulates production of OGF and OGFr for subsequent interaction following blockade of the receptor. The OGF-OGFr axis may be a feasible target for treatment of cancer of the ovary (i) in a prophylactic fashion, (ii) following cytoreduction or (iii) in conjunction with standard chemotherapy for additive effectiveness. In summary, preclinical data support the transition of these novel therapies for treatment of human ovarian cancer from the bench to bedside to provide additional targets for treatment of this devastating disease.

Let me know what you dig up, SelenaWolf, I'll be interested to read it!

I just stumbled on this thread, doing a search for something else around here. Really interesting! I have read before that LDN has promise for cancer treatment. 

I am on LDN (1.5 mg - I'm a light weight, weigh 85 lbs) for Crohn's disease, and that dose of LDN, later combined with Moducare and some dietary modifications, put me in remission. I tried each of those alone (LDN, Moducare, and the dietary changes), and only with LDN did I have a very marked improvements in symptoms. The addition of the other 2 did help though. But when I took LDN away and kept the other 2, I started going back into flare mode within less than a week! Second most helpful was the diet, the Moducare makes the smallest difference, but enough for me to stay on it.

Anyway, I'll go and read those articles linked here too. There is some mention of the use of LDN for cancer on http://lowdosenaltrexone.org/ , but I forgot if there are any links to clinical trials or studies for that use, it's bee a while since I read it.

Well, I wasn't able to find too much out with regards to LDN and breast cancer, specifically.  The only action on LDN right now - at least in Canada - appears to be in the areas of addiction, alcoholism and Crohn's Disease, with some research geering up in the areas of autoimmune diseases, such as rheumatoid arthritis and HIV/AIDS.  There was nothing (that I could find in the two hours' I was there, which means only that I didn't find the information not that the information may not have been there) about why any of the cancer-related LDN studies were terminated.

In the pharmaceutical industry - again, at least in Canada - all company's have a "compassionate use" program when it comes to access to experimental (i.e., still in clinical trials), which appear to be promising.  These substances are provided to hospitals, doctors and patients free-of-charge.  However, the major concern of the pharmaceutical companies and the Health Protection Branch is the continued safety of the patients.  Sometimes - even if the research-to-date is promising - there are "kinks" that haven't been worked out yet: issues concerning safe dosage, dangerous interactions with other medications/conditions, quality-of-life issues, etc.  Even a promising substance has the potential to be dangerous under certain circumstances, especially when someone's physical conditional has been compromised by illness and other comorbidities.

In addition, just because an established substance - such as metformin or LDN - has proven "safe" and "effective" for other well-documented issues, does not mean that it will continue to be safe- and effective for off-label uses.  Substances are researched thoroughly, tested thoroughly and pass regulatory controls because they have been proven safe- and effective for specific conditions under hightly controlled environments.  Just because a drug operated very well under those conditions, doesn't mean that it doesn't have the potential to fail under different conditions.  I think I've mentioned before working on a clinical trial for what was shaping up to be a central nervous system "wonder drug" for depression.  The early results were spectacular; so much so the drug was fast-tracked by both the company and the Health Protection Branch.  Everyone was giddy at the performance of this drug and it's lack-of-side effects in clinical trials.  However, when the drug hit a wider population in a less controlled environment, an irreversible side effect emerged within three months: partial facial paralysis.  The drug was pulled and all clinical trials halted.

Although metformin safely works for diabetics and LDN works for alcoholism and drug addiction, it does not necessarily mean that it will perform the same way for other medical conditions.  Once you want to look at how a substance works for these other conditions, then it is imperative that you apply that off-label use to the same rigorous exploration as you did the first time.  Anything else would be irresponsible and unethical and, frankly, not logical.  I mean, why would you insist that a drug be proven safe- and effective for one thing, yet demand that - because it is safe- and effective for that one thing - you have the "right" to circumvent further testing- and research for another thing because for the first thing, it works.  Even if the theory is logically sound - such as the off-label use of metformin to lower the risk of recurrence in breast cancer and LDN for the same reason - it still needs to be tested to make sure that, what is basically an assumption (logical or not) will, indeed, perform as hoped under different circumstances.

I'm reminded of something one of my pharmaceutical colleagues said once.  He was a brilliant man: he had completed a medical degree with a speciality in oncology, a dental degree with a specialty in oral surgery, and a PhD in Pharmacology, and had taught pharmacology in university.  We were having a discussion about the whole thorny issue of "compassionate use" and "right-to-try" movements, and he said that one's "right" to try an untested drug, often infringes on the "right" of someone else to safe- and effective medical care, and - definitely - on the rights of others to ensure that that care is safe- and effective. 

We, often, forget that in championing our "rights" to do something, we trample on the "rights" of others to something else.

Just ran across this study about LDN and the immune system: http://www.ncbi.nlm.nih.gov/pubmed/24455776

"Our study has provided meaningful mode of action on the role of LDN in immunoregulation, and rationale on future application of LDN for enhancing host immunity in cancer therapy and potent use in the design of DC-based vaccines for a number of diseases."

I think the Science Daily article about OGR and triple neg BC had the wrong study linked to it at the bottom (that was related to ovarian cancer.) I found the abstract for the right study on pubmed:  http://www.ncbi.nlm.nih.gov/pubmed/23918871

It mentions that, "TNBC cell lines MDA-MD-231 and BT-20, as well as human breast cancer cells SK-BR-3 and MCF-7, were examined for the presence of pentapeptide and receptors, as well as their response to OGF." But then it says nothing on what the results were for the HER2+ line (SK-BR-3) or the ER+ line (MCF-7). Weird.