Which mutations work for Adapt?

[Cherie]

Hi Does anyone know what mutations work with ADAPT? Also dose anyone know where I can go to get dosing information I'm fast running out of options.

[Sophy]

Hi Cherie,

I don't know which mutations work for ADAPT, my onc in Wellington contacted Dr Lin's office by email and they said to add 200mg of celebrex twice a day to the xeloda (which I am taking 2000mg per day). The celebrex may be doing nothing to prevent cancer growth but I have found it is good at helping with the pain from my thoracotomies last year. If you are still in pain maybe you could have it prescribed for pain relief even if your onc doesn't believe in the anti cancer effect?

I also take cimetedine which may or may not help with preventing cancer but it has had the unexpected effect that I am no longer as sensitive to my dog's fur which is great. And also as an antacid it helps prevent stomach irritation from the celebrex.

Let me know if I can help with any more info

Sophy

[Nik Colon]

Not sure if this will help, but here is a link
https://clinicaltrials.gov/ct2/show/NCT01729923

[skypup]

Hi Cherie, my dear kidnappee. ADAPT is generally 200mg celecoxib twice a day and 1000-1500mg Xeloda twice a day. Generally it's two weeks on and one week off, thought that seems to vary a lot. At least that is what I found by quizzing the folks here and checking Dr Lin's stuff and the clinical trials. As far as mutations, I don't think KRAS, NRAS or BRAF matter (from what I've read), but my FoundationOne report told me that mutated P13K indicates celecoxib may be advantageous. I'm not sure from what I've read that ADAPT is going to be very helpful for folks like us, that it may be more useful in people with very low tumor burden or those trying to stay NED, but I figure why not try, right? I am very much looking forward to my next scan in two months.

Are you able to get out and about? Is your energy level still bottomed out? I'm sending you the best wishes!!!

[vilca11]

Hi Cherie,

I am very sorry to hear about the spread. Xeloda dose in Dr. Lin's ADAPT protocol is 1000mg/sq m of Body Surface Area (BSA). You can calculate your BSA here http://halls.md/body-surface-area/bsa.htm

You can take a lower dose too, about 1000mg less than the calculated one. Celebrex has a very serious affect in that protocol, it is not just for alleviating hand/foot syndrome. Celebrex, according to Dr. Lin and his clinical trial concept, "pulls" cancer stem cells from the bone marrow, where they are hibernating and hiding from chemo and gives Xeloda a chance to kill them.

Dr. Lin insists that tumor burden of the patient was at absolute minimum at the start of treatment. So, Skypup is right, one has to be NED or almost NED for ADAPT to be successful - it is a maintenance therapy, not a curative therapy. I would say, write a PM to rp1954 and tell him about your situation, asking for his help. May be he will be able to advise on a better way in your situation.

Sending you big hugs and warmest thoughts. I will be thinking too of what else could be done and post here after some research. Vilca

[vilca11]

Forgot about mutations. I think, it does matter what mutations patient has, Dr. Lin does Oncoplex test (genetic test) for all his patients. I do not have much mutations, only TP53 (typical for majority of CC patients) and APC alteration (also typical), and that was OK for ADAPT. PM to Maia, she might know for which mutations ADAPT does not work. Vilca

[rp1954]

The quickest way to estimate whether your 5FU based chemo works, including adequae dosed ADAPT with celecoxib, is to directly watch for the rise in your MCV values every 2-3 weeks for 4-9 weeks. Everything else is likely to be slower or bigger guesswork right now.

[vilca11]

A. - you mean MCV has to go above the norm range? or rise within the norm range? the top of the range in Hopkins is 96, mine was 103.3 without resuming Xeloda. So, now what?

Hugs, s

[rp1954]

Since high MCV value is usually an indicator for macrocytic anemia in people off chemo, for folate and B12 (in)sufficiency, that 103 is something I would get an opinion on.

We can temper MCV down a few points by degree of liver consumption - yum ; genuine macrocytic anemia patients might normally expect bigger downward changes on folate(B9)-B12-liver treatment. The MCV-chemo papers are from scattered sources across the last 1/3 of a century. Basically, most patients probably start 75-95. 5FU/X moves the count up, the higher the happier the odds. Adding another good modulation treatment, a few more points up, for each. With Xeloda alone, "...median ΔMCV level was 9.1 (min-max: -2.4 to 24.9) among patients who had clinical benefit and 5.90 (min-max: -0.8 to 12.3) among nonresponders"

Exhaustion of a treatment series and the MCV drops like an artillery shell coming back down; or any tx fubars, MCV drops. I've seen published MCV-chemo over 120; in the 110s I do worry that more than cancer cells are being pummeled.

[lpas]

Since high MCV value is usually an indicator for macrocytic anemia in people off chemo, for folate and B12 (in)sufficiency, that 103 is something I would get an opinion on.

We can temper MCV down a few points by degree of liver consumption - yum ; genuine macrocytic anemia patients might normally expect bigger downward changes on folate(B9)-B12-liver treatment. The MCV-chemo papers are from scattered sources across the last 1/3 of a century. Basically, most patients probably start 75-95. 5FU/X moves the count up, the higher the happier the odds. Adding another good modulation treatment, a few more points up, for each. With Xeloda alone, "...median ΔMCV level was 9.1 (min-max: -2.4 to 24.9) among patients who had clinical benefit and 5.90 (min-max: -0.8 to 12.3) among nonresponders"

Exhaustion of a treatment series and the MCV drops like an artillery shell coming back down; or any tx fubars, MCV drops like rock. I've seen published MCV-chemo over 120; in the 110s I do worry that more than cancer cells are being pummeled.

Very interesting, rp. Thanks for posting this.

[vilca11]

Thanks much, A. The fact that disappointed me in the link you provided is that OS was not really affected much... so, what's the point - response, no response... We are after OS and QOL, mainly... what a horrible disease..so many suffer so much...

[rp1954]

The average response for non-optimized xeloda alone wasn't that great. Maia's references show night and day performance differences between xeloda alone (months) and ADAPT, xeloda+celebrex, for extra years. I use ΔMCV kind of like a thermometer for chemo activity.

The first issue is whether something works at all, then we can optimize or move on to add or try something else. In our experience, ΔMCV with and without celecoxib were pretty clear changes, slightly faster than CEA and CA19-9 which would still peak two months after adding celecoxib and take 1-2 more readings (months) to clearly show that CEA/CA199 peaks had occurred. Also multiple kinds of data agreement re-assure more after the (expected) peak.

[pukalania]

Hi Cherie,
I sent you a PM..my hubby is currently doing 1500 xeloda, 200mg celebrex, gensitein every day no break and avastin every 3 weeks..purpose is to slow growth...
xoxo

[Cb75]

I just sent my pathology slides to Dr. Lin for his review and consideration. I was lucky enough to speak with him on the telephone a few months back to discuss my situation. Based on what I told him, he advised that he thought i would be 'ideal' for his trial, or at a minimum to try his protocol. I am in Toronto, Canada, he is in Seattle, which would make it difficult to join the trial. He also mentioned that he has seen some good results in KRAS mutants. I know I have the KRAS mutation. I've had my tumor samples tested from my primary, and my liver and was told that the only mutation I have is KRAS. I am curious to see what Dr. Lin's testing shows. I hope to see him in the next few months to see if this is an option for me.

Carmen

[vilca11]

Hey Carm, glad you are going to engage with ADAPT and as a good candidate! That is a good piece of info for others that it works for KRAS.... Are you currently NED? What supplements you are taking now?
Hugs, Vilca