Antibiotics, PPIs and chemotherapy drugs each damage the microbiome and the immune system, reducing the effectiveness of immunotherapy drugs and increasing the potential for liver toxicity.
Using chemotherapy drugs at the same time as Immunotherapy drugs is insanity
What was it that Einstein said? Something about repeating the same thing over and over again and expecting a different result?
As regular readers will know, I believe immunotherapy drugs are the way forward. They can be excellent if used properly. I have written on how to make you immunotherapy drugs work properly. It’s not rocket science - it all comes straight out of multiple immunotherapy research studies.
There are at least 6 studies showing that a high fibre diet makes PD-1 drugs like Pembrolizumab work better. Then studies showing vitamin D supplementation makes PD-1 immunotherapy work better; and, only recently, that taking a butyrate supplement does the same.
It's a chain reaction. Gut bacteria love soluble fibre; the bacteria that make butyrate especially; their numbers increase (5). And butyrate activates the vitamin D receptor and the vitamin D from the inactive form in the body (6), and vitamin D is crucial to activating your T-cells (7) improving the attack on your cancer. Bingo. The PD-1 Immunotherapy works properly.
The problem is we are NOT using these great drugs properly.
So why, if drugs like antibiotics and PPIs are known to damage the attack on cancer cells, would someone think using chemotherapy would get a different result?
It doesn't.
Why then would any science-based oncologist believe taking chemotherapy drugs at the same time as a PD-1 would not also reduce the effectiveness of immunotherapy drugs?
At this point I hear oncologists shout, “Yes, but we have a clinical trials.”
Really. Let me give you some examples of the problems patients are facing. And oncologists know these only too well.
Example 1: About two years ago, I reported on cancer patients being given a double immunotherapy - Nivolumab and Ipilimumab, or Nivolumab plus a PD-L1 monoclonal antibody. It might have been a clinical trial. What happened was that two of my patients had a liver toxicity problem, albeit mild. and had to stop the drugs.The toxicity went away in two weeks. At about the same time, I had five male patients come to me. They had all had terrible Liver Toxicity problems following the double immunotherapy, necessitating not just cessation of the drugs but the use of the steroid Prednisolone for four months. They still had the problems In each case, whether they lived in Scotland or Devon. They had been told by their oncologist that this was the first time the oncologist had ever heard of it happening.
Example 2: More recently we are seeing a new treatment protocol, which seems to be unique to Britain. Patients are being given two chemo drugs plus an immunotherapy for 3-4 rounds and then continuing with the Immunotherapy drug (Pembrolizumab) on its own. But here we go again. I've had a number of patients come to me with liver toxicity problems after the 3-4 starter rounds. And as a result they were offered Prednisolone and no longer allowed the immunotherapy option.
My patient expressed concerns to his oncologist about having chemo drugs at the same time as an immunotherapy drug. He was told by the oncologist that in the Clinical trials, the Pembrolizumab didn’t work on its own, but when the researchers used two chemo drugs with it, they found a significant response after 3 months.
So I went to read the clinical trials.This is NOT what they said. The immunotherapy worked on its own reducing tumours by about 23 per cent after 3 months; usuing the immunotherapy increased the tumour reduction to 36%.
There were warnings on liver toxicity.
I would like to make a couple of points:
Immunotherapy is capable of doing something most chemo drugs cannot. Immunotherapy can cure a cancer - I’ve seen it with Colorectal cancer and ‘mis-match” genes; and with Melanoma, and with NSCLC.
If you want it to work at its very best, your patient needs a wonderful microbiome and high levels of activated T-cells. Unblocking a low level of weak T-cells is not going to do much for you, is it?
We have research from the USA - 2 drugs taken for 4 rounds, then antibiotics for 2 weeks. One year later how much of a microbiome would the patient have. An oncologist guessed that after a year it would have recovered 85%; I said 40%; the research said 27%. 4 rounds of chemo and 2 weeks of antibiotics destroy three quarters of a healthy microbiome. Without a healthy microbiome, immunotherapy will not work to its potential.
Liver Toxicity
And this is my second concern. Liver Toxicity. It is equally important. The oncologists damage the microbiome and the liver. Liver toxicity can occur with chemo; it’s one of the reasons oncologists do blood tests. But it can also occur more with immunotherapy drugs or Immune Checkpoint Inhibitors (ICIs) to give them their correct oncology title; Ipilimumab seems worse than others. In one study, ALT was elevated in 6.2% in the nivolumab group and 14.6% in the ipilimumab group; the most aggressive toxicity was found in 1.15% and 5.7% patients respectively. AST was elevated at 0.4% and 4.2% respectively. Pembrolizumab seems the 'safest' for liver toxicity.
Research reviews talk of an ‘overactive immune response’. ICIs boost the immune system by unblocking the blocks that cancer has put in place, causing increased inflammation and cytotoxicity against the cancer (and the liver). In my opinion, this is because you have to take things slowly BEFORE you use immunotherapy drugs. If oncologists understood the microbiome and its effects on the immune system, they would realise why I like to rebuild the patients microbiome, their soluble fibre consumption, butyrate and vitamin D levels. There’s research on all of this. Rebuilding the microbiome gets an improved immune system working, so the immunotherapy drugs DON’T cause such a shock to the system!
Correcting Liver Toxicity - Prednisone, Prednisolone
Steroids are considered ‘First Line Treatment’ for Liver Toxicity - the dose depending upon the grade. Hepatitis is a serious issue and guidelines in the USA include investigation for viral hepatitis, history of alcohol use, iron stores, and liver imaging (in case of potential liver metastasis).
If the patient has high liver toxicity, the Doctors reach for the Prednisone. Doses up to 60 mg are given. There is a very useful research review (3) on ICIs and liver toxicity.
On the subject of Prednisone, one study (4) showed that the steroid didn’t seem to add anything to recovery times. .Worse, the people who did not take Prednisone, on average recovered after 4.7 weeks; those who took the drug recovered after 8.6 weeks on average. So much for the steroid!
Prednisolone doses greater than 60 mg don’t improve the recovery time either. And having had both Nivolumab and Ipilimumab actually extends it.
NB. Both Prednisone and Prednisolone are synthetic versions of cortisol, the stress hormone! Prednisone is the precursor of prednisolone.
Go to: Overcoming Liver Toxicity - eight natural compounds that can help
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References
1. Influence of Microbiome and Antibiotics on the Efficacy of Immune Checkpoint Inhibitors; Priyanka Patel et al; Cureus. 2021 Aug; 13(8): e16829.
2.‘Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer; David Pinato et al. JAMA Oncology. DOI: 10.1001/jamaoncol.2019.2785
3. Immunotherapy-induced Hepatotoxicity: A review; Teresa Da Cunha J Clin Transl Hepatol. 2022 Dec 28; 10(6): 1194–1204.
4. Immune-related hepatitis with immunotherapy: Are corticosteroids always needed? Marie-Léa Gauci et al; J Hepatol 2018, Aug 69 (2) 548-550
5. The Health Benefits of Butyrate; Cleveland Clinic
6. Active Vitamin D Levels Linked to Gut Microbiome; Deborah Kado, UC San Diego; Genetic Engineering and Biotech News; 1 September 2020
7. Vitamin D crucial to activating immune defenses; University of Copenhagen. ScienceDaily, 8 March 2010. .
8. Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis; Nicholas A Scott et al; Science Translational Medicine, 24 Oct 2018, Vol 10, Issue 464
9. Post-chemotherapy T-cell recovery is a marker of improved survival in patients with advanced thoracic malignancies; MJ McCoy British Journal of Cancer volume 107, pages1107–1115 (2012)
10. Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer; Rashimi Verma; British Cancer Research
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