Dear Rene and Edward,
first of all: thanks for an amazing book and thanks for sharing your truly inspiring story. We are on a similar journey as you, and it is great to learn and be inspired from what yo have done.
My wife, 32 years old, was diagnosed with stage IV lung cancer in March last year. She had metastasis in both lungs, lymph nodes, bones and brain. She luckily had the EGFR mutation which was possible to treat with the targeted drug erlotinib (Tarceva). However, this only lasted 5 months: progression of the main tumor in her lungs were seen on the CT scan in August last year. We then decided we had to do more - much more - if we were to have any chance at all in defeating this beast.
We first tried a combination of stereotactic radiation and immunotherapy. She had the main tumor in the lung radiated (it was the only one growing), and we added nivolumab (normal dose) and one injection of ipilimumab as well (1 mg/kg). In parallell she also continued erlotinib. This worked well for a couple of months, but in November she developed a persistent cough and a CT scan showed what was suspected to be pneumonitis. She had to stop nivolumab, take methylprednisolone, and continued only on the erlotinib. In January this year she progressed again, this time both in the brain and in the lungs.
We then switched to another targeted therapy called osimertinib (aka Tagrisso) as she had a mutation that made her cancer sensitive to this. She also had stereotactic radiation for the brain met. This shrank the tumors, but we are acutely aware that osimertinib only works for some months (8 months in average for patients with brain mets) and we have since continued pursuing immunotherapy. We came across a project in Germany that develop personalized peptide vaccines (based on tumor specific mutations identified through whole exome sequencing). We jumped on this and in June this year my wife started receiving injections with this vaccine. In addition she is also getting low dose nivolumab and low dose ipilimumab.
Scans since June have been good. No new lesions and no growth. However, a few weeks ago my wife developed quite a bit of rash on her arms and legs. This got so severe it had to be treated with Elocon, and our doctor has put the nivolumab infusions on hold. She is still getting the vaccine injections. Over the last couple of months my wife has also lost a little bit of weight.
When it comes to diet, we don't really follow any very strict diet. We try to eat whole meal bread, and brown pasta instead of white (probably the words I use here are not correct, but hopefully you understand...). My wife is also taking fish oil, around 6 capsules each containing 625 mg of omega-3 per day (so a total of around 3.7 grams per day). She is also taking probiotics and sometimes also vitamin D and calcium.
Finally, she is also taking the following "re-purposed" drugs: metformin, fluvastatin, mebendazole, celecoxib and auranofin. The three first of these are part of a protocol developed by Care Oncology Clinic in London. Celecoxib is due to both anectodal and pre-clinical evidence indicating this may be beneficial in EGFR positive NSCLC, as well as pre-clinical evidence it may be synergistic with immunotherapy. Auranofin is also based on pre-clinical evidence indicating it may be beneficial in EGFR positive NSCLC.
I then have a number of questions, I hope not too many...:
-Would you have any thoughts on whether Coley's toxin could make sense to add to the mix?
-Do you have any thoughts on whether combining immunotherapy with a targeted therapy such as osimertinib is good or bad? Are there reasons to believe that targeted therapies somehow detract from the immunotherapy? We have been wondering if we should stop osimertininb, but have basically not dared to do so yet.
-When reading your book, I was wondering if my wife may currently be suffering from "chronic inflammation", and hence perhaps the high dose fish oil and low intake of omega 6 can make sense. How did you go about to determine that Rene had a chronic inflammation? We have not done anything in particular to reduce Tregs or MDSCs, and if this can be achieved with high dose fish oil, it seems an attractive complement with the immunotherapy she is currently doing (maybe in particular now that nivolumab is on hold).
-Did you only do the ketogenic diet for a few weeks? And do you believe it helped? If you stopped it, what was the reason for that? And would you think a ketogenic diet could make sense in our case? I guess maybe one would have to stop the metformin.
-We are looking into doing an intratumoral injection in the main tumor in the lung (the same that was radiated). We are discussing this with a doctor in Germany. Can I ask if you have any thoughts on what could be good to inject into a lung tumor?
-Can I ask if you have any thoughts on sodium bicarbonate? I recently came across this article from some researchers at Moffitt: Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy (https://www.ncbi.nlm.nih.gov/pubmed/26719539).
-Can I ask if you have any thoughts about high dose IL-2? There is a doctor in Vienna that is using this in combination with other immunotherapies: http://meetinglibrary.asco.org/content/166013-176.
Apologies for asking so many questions...
Kind regards,
Lars Soraas
(Oslo, Norway)