Vitamin K and EGFR inhibition Concern - 1261619

Hello Will, From what I read of your link it does appears the research was done to find an association between K and reduction of skin rash. What was found was given internally it may cause EGFR inhibitor to be less effective but an initial study such as this is far from conclusive. What I understood is it's reversible. In the discussion they say it may be best to try a topical cream with K. But juicing with high K foods could explain why your mom's rash is better. Dr. West wrote a post on it here. http://cancergrace.org/cancer-treatments/2008/04/13/menadione-for-egfr-…

A lab study hasn't proven that K will decrease efficacy but too much of anything has a chance becoming harmful.
Such as, the body uses K to clot blood. Since lung cancer has a tendency to cause life threatening clots I'd think too much K could be harmful.

I'll ask a doctor to comment.

All best,
Janine

Right Will, there has been quite a lot written on the subject here as well though it's not at all a 1 to 1 correlation and there are many with the rash who progress and many to remain stable even though the rash has healed. I've asked Dr. Walko our oncology pharmacologist to comment though I imagine it will take her a bit of time to answer since it's Saturday and she's just settling in from a move to a new town.

I just commented on the K as it could also affect clotting which can be a hazard for those with lung cancer. As I understand it's one of the vitamins that can be easy enough to extract from food.
I wonder if she could use other veggies not as high in K. I juice mostly carrots with dashes of garlic, celery lemon juice, so not especially packed with K but most certainly gives a quick burst of energy.

Janine

The story of rash and EGFR inhibitors is complex, as Janine indicated, and not remotely as simple as "more rash --> greater benefit". I know of no real evidence that juicing or vitamin K worsens clinical outcomes in patients with cancer (and I am not remotely swayed by the findings of a preclinical study, which I would not presume has almost any correlation with clinical results in real patients), but I also know of no data to show that juicing helps patients with cancer live a day longer. I'm afraid that both of these questions -- whether juicing is beneficial and whether vitamin K diminishes efficacy of Iressa (gefitinib) or other EGFR inhibitors -- are devoid of good clinical evidence to direct any recommendations, to the best of my knowledge. Most oncologists tend to veer toward a recommendation away from any major dietary intervention beyond a balanced diet, since we have more findings of vitamin supplements leading to detrimental effects in cancer than beneficial ones.

Good luck.

-Dr. West

Hi Will,

As Dr. West said, there just isn't enough evidence (either way) about whether any of these foods or high amounts of vitamin K interact with EGFR inhibitors. If you are worried about vitamin K it certainly makes sense, as Janine suggested, to juice the foods you've listed which are relatively low in vitamin K.

My wife's cancer nutritionist advised against taking high doses of vitamin supplements, feeling that it was better to get those vitamins through natural (food) sources.

JimC
Forum moderator

Iressa has sold over 50 million tablets in 80 markets worldwide, so there is a fair amount known about it. My understanding is that the pill absorption is not affected by food. There doesn't seem to be evidence to suggest that cruciferous vegetables interfere with drug absorption or antagonize the drug. Hope this helps.

Thanks Dr. Creelan, It's been a consistent mantra on Grace that grapefruit is the only food that affects iressa and tarceva and I think now afatinib. All else is fine, juiced or not. If you'd want to play it safe, like Jim said, the veggies you listed above wouldn't have K in amounts that could possibly have an effect like supplemental K.

I don't juice everyday only about weekly. It's very costly so we keep mostly to salads and cooked veggies for that part of our diet. When I juice it's usually carrot, celery and ginger with a squeeze of lemon. I choose those mostly for taste and the type of juicer I have doesn't masticate things like leafy greens. When drank asap I like to think it adds heaps of fresh nutrients not easily absorbed when eaten. One word of caution Will you didn't ask for, I hope you make sure your mom enjoys her eating experience no matter what it is. It's so much more difficult to find enjoyment in life when facing incurable cancer and for some many food is an easy fix.

Janine

Follow up on Dr. Walko, I corresponded with her and she is indeed out of contact. She said she would reply when she got a moment though had nothing to add to what's been said. I suggested she not respond so not interrupt her adventures.

Janine

I've periodically been checking on the status of the research on vitamin K (k1 and k3) for nearly 3 years.

=== Topical Vitamin K3 (menadione) ===

Here is the 2011 article that originally drew my attention to this subject:
http://www.ncbi.nlm.nih.gov/pubmed/21914790
(Although it was retracted in 2013 due to some image alternation, the details of the retraction indicate the other authors had the experiments re-run by an independent 3rd party and given the results were consistent with their previous data results they stand by their original conclusions.
http://www.ncbi.nlm.nih.gov/pubmed/24003062 )

In 2011 I even contacted Roman Perez-Soler to get more details on that pre-clinical research on menadione (vitamin K3). His team's work reported that k3 overcame and abrogated the effect of EGFR inhibitors in vitro, and K3 was about 10 times as potent as K1 (the type in vegetables). K2 (the type in certain in fermented products) did not have the effect. Since then there have been trials on both topical K1 and topical K3.

I have not found any reported results for the phase 1 trial of topical K3, but this is its description:
http://clinicaltrials.gov/ct2/show/NCT00656786
and here is the phase 2/3 trial at the Mayo Clinic:
http://clinicaltrials.gov/ct2/show/NCT01393821

Today a patient's husband alerted me to this new article, though, indicating that in an ex-vivo lab experiment (i.e., testing on skin samples) systemic absorption of topical menadione (K3) was negligible:
http://www.jaad.org/article/S0190-9622(14)00634-3/abstract
(I don't have access to the full article, just the abstract so I don't have more details.) Given that, he asked his oncologist whether this research might be of use for his wife's rash issues, and the oncologist decided he was willing to let them try a prescription of 0.05% menadione topical lotion. I expect I'll hear how it turned out in a few weeks.

=== Topical Vitamin K1 ===
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(. . . continuing . . . )

Before I go on, I should add that if there were any systemic absorption of K3, the 2011 lab experiments suggest it would not be prudent to risk trying K3. I don't know if a single ex-vivo study that the systemic absorption is minimal should be completely trusted on that point, and would prefer clinical trial results with enough people to calculate whether duration of EGFR inhibitor benefit seems unchanged by use of topical K3 on rash-prone areas.

=== Topical Vitamin K1 ===

Back in 2011 I heard of one trial of topical vitamin K1 in Italy which I couldn't find details on, but now (as of a year ago) there was a new review article that offers a summary of the research on topical K1 (& K3) within it so I'll defer to that article:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691090
(Scroll far down to the section just before the Discussion section.)

A quote from that: "To date, there have been four observational studies investigating the topical application of 0.1% vitamin K1 cream, three reactive and one prophylactic. In all three reactive studies good control of EGFR-targeted therapy-induced rash was observed. . . . In the prophylactic study61, the use of vitamin K1 cream (0.1% bid) applied to the face and chest was very effective at reducing the severity of cetuximab-induced skin toxicity . . . ."

Suffice it to say, there seems to be a real effect on EGFR rash when topical K1 is applied topically.

=== Consumption of Vitamin K1 ===

(. . . I'll continue a new message to break up my comments . . . )

(. . . continuing . . . )

=== Consumption of Vitamin K1 ===

Now when you consider whether consuming vitamin K1 could have a negative effect we're probably entering the world of logic and anecdote rather than trials. I don't expect there are many people who would want to offer or try a trial that is testing whether something could do harm.

Logically, the pre-clinical research and trials on vitamin K1 suggest it might not be good to get a lot of it in your system. But that doesn't say what "a lot" is. But we do know that EGFR inhibitors worked wonderfully in their clinical trial, and most people in the trial probably followed a "normal" diet, including probably a "normal" level of vitamin K1 from things like dark green leafy veggies, broccoli, cucumber, even tea leaves if they consume the leaves. (It's not soluble in water, so if tea leaves are filtered out so it the K1, or so I've read right or wrong.)

Based on that logic, a normal level of K1 in ones' diet doesn't seem likely to be a concern, at least not compared to the normal range of duration for EGFR inhibitors, and maybe not for types of resistance that aren't due to EGFR variants.

Anecdotally, though, I've know of two ALK/ROS1 people who reported a transient return of a telltale cancer symptom after eating a large amount of broccoli - a K1-rich food. I was one of them (about 10x a normal amount of K1 in one bowl, and resulting in a return of fluid-in-lung production for a few hours), but I'll spare you the details (and the connection between EGFR stimulation and ALK or ROS1-driven cancer) since unsubstantiated, un-validated anecdotes aren't reliable, and possibly caused by something different than assumed. But I will say that since then (2011) I've limited my K1 dietary intake (and broccoli in particular) to at most a normal amount and usually less, and the symptom has not returned since (not that that proves anything).

Best hopes,

Craig in PA