Iressa, naturopathic remedies, and elevated liver enzyme levels - 1257948

hain
Posts:113

Hello,

My mom has been on Iressa for about a month now and is doing very well subjectively and objectively (recent X-ray reported moderate interval improvement). However, her recent blood test results indicated some issues with the liver - elevated AST and ALT levels.

Specifically: AST = 52 (normal range 10-42) and ALT = 114 (normal range 0-30).

We were informed by the oncologist that although this is believed to most likely be due to my mom taking Iressa (as previous months blood work was fine when she was not on Iressa), it was indicated that they are ultimately unsure if the naturopathic remedies my mom is on has any contribution to this elevated level of liver enzymes (by its interaction with Iressa or on its own). Hence, we are given the option to either continue on with all naturopathic remedies until the next 3 week follow up (August 1) and obtain blood work and make a decision then, or to stop all naturopathic remedies and obtain blood work at that time. The second option would help to see whether or not there is interactions between the naturopathic remedies and Iressa contributing to the elevated enzyme levels.

I am really unsure on what to do with this information and the decisions around naturopathic remedies and Iressa. I know for sure Iressa is definitely beneficial for my mom as she is having great response to it. However, I also understand the nautropathic remedies may have also helped her to feel better in the past and possibly currently. I am hoping you could offer some opinions on this matter.

Here is what she is currently taking for her naturopathic remedies (prescribed by her ND):
- Curcumin 3g/day
- Vitamin D 5000IU
- Fishoil 2g/day
- melatonin 20 mg/day

She is also taking papaya leaf extract tea, approxiamtely 30g/day, concentrated from 3L to 750mL, brewed for 3 hours. This tea is not prescribed by her ND but he understands she is also currently taking it.

Looking forward to hearing back from any advice.

Best regards,
William

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Reply # - July 16, 2013, 06:43 AM

catdander
Posts:

Hi William, I'm very sorry to know your mom and you are going through this. I don't think we will be able to say which med might be contributing to her elevated levels or whether it may be a combination of them. Nor can we tell you should do, it's illegal for our faculty doctors to advise someone who isn't their patient.

However, I will ask our pharmacologist to comment.

In all stage 4 lung cancer treatments the goal is to extend life and add quality. There's no doubt that iressa has the ability to do that, it's been extensively studied and shown to support these goals. The supplements, while may add benefits, there isn't close to that type of evidence to think they outweigh iressa's ability to lengthen and add quality to your mom's life.

It makes sense to drop one of the treatments to see if there’s a change in blood levels, it's not unusual for people to take treatment breaks if treatment is too difficult. It would seem less dramatic for her to stop the supplements first. It’s very possible to advance so quickly off iressa that it’s impossible to recover ground and stabilize, while this isn’t likely to happen if she were to stop the supplements. Either way keep a very close eye for any downward trend. I hope she recovers soon and this is just a bump in the road.

All best,
Janine
forum moderator

Reply # - July 16, 2013, 07:34 AM

hain
Posts: 113

Hello Catdander and Dr. Walko,

Thank you for your quick replies to my question.

I should probably add that my mom's ND recently suggested that my mom stop the curcumin supplements and instead commence milk thistle (silymarin) which is a liver support herb.

No additional advice was specified in regards to the other remedies, but I am assuming he would like my mom to continue the rest.

I am wondering what your thoughts of are in this matter? Looking forward to hearing back from anyone with advice. Much appreciated!

Best regards,
William

Reply # - July 16, 2013, 09:33 AM

dr walko
Posts: 102

William,

A PhD student I recently worked with actually specifically looked at interaction potential with milk thistle and other drugs. It was shown that milk thistle also can interact with the Iressa and cause increase side effects since it can prevent clearance of the iressa from the body. I don't think there should be a problem with the other agents.

best wishes,
Dr. Walko

Reply # - July 16, 2013, 04:19 PM

hain
Posts: 113

Dear Dr. Walko,

Thank you for you reply.

I was wondering if you could possibly direct me to the references you are referring to in terms of the interactions between milk thistle and iressa - I'd be interested in having a read myself.

In terms of the other agents, do you think my mom should continue taking the papaya leaf extract? How about the melatonin, Vitamin D, and fish oil? Or do you think its best that she stops all the naturopathic agents and take only the iressa until the next 3 weeks follow up? I'm just afraid that her liver enzyme levels would continue to steadily increase and she would be forced to stop it as she is currently doing so well on it.

Thank you for your reply in advance.

Best regards,
William

Reply # - July 16, 2013, 04:26 PM

Dr West
Posts: 4735

I'm sorry I can't offer any insight here, but I need to advise that we can't answer "should" questions. We are legally prohibited from telling people who aren't our patients what they should do in the management of their own cancer. That is a judgment that is between the patient, their doctor(s), +/- other caregivers involved.

Thanks for understanding.

-Dr. West

Reply # - July 16, 2013, 05:44 PM

hain
Posts: 113

Hello Dr. West,

Thank you for your reply.

I certainly understand where you are coming from and that you are unable to give definitive advice on specific medical treatments since my mom is not your patient. However, I was just curious as to what your expert opinions are, which would help us to ultimately make a more informed final decision. We tried contacting my mom's oncologist's office, however, we have not received a reply yet in 2 days. They seem quite busy and so in the meantime we are just seeking out any alternative ideas to help us in our decision making process. Further, the last conversation we did have with the hospital pharmacist there, she was unsure of the interactions and basically left it up to us to decide whether we would like to continue or not continue any of the naturopathic remedies. Hence, our dilemma and difficulty in making a particular decision on this matter.

Looking forward to hearing back from you.

Best regards,
William

Reply # - July 16, 2013, 06:08 PM

Dr West
Posts: 4735

I have no definitive information but think there is not likely to be a significant negative interaction melatonin, vitamin D, or fish oil and an EGFR inhibitor. I personally have absolutely no enthusiasm in the world for favoring papaya leaf extract, for which I know of no remotely meaningful evidence to suggest it would be a beneficial intervention, so regardless of whether it interacts with Iressa or not, it's not an agent I feel I would go so far as to recommend here.

-Dr. West

Reply # - July 16, 2013, 06:15 PM

dr walko
Posts: 102

William,

Regarding the interaction between Iressa and milk thistle, Im not sure if my PhD student's work has been published yet (I reviewed it in his dissertation recently). The way that interaction trials are done usually is to assess a drug's ability to inhibit certain liver enzymes in the test tube basically. Sometimes "probe drugs" known to be specifically metabolized by a certain enzyme are also used. These type of studies have shown a good deal of predictability for drug interactions. So, it is unlikely that a trial specifically looking at milk thistle and drug concentrations of Iressa will be done. We use these other surrogates to determine the liklihood of interactions since they are more broadly applicable.

Iressa is metabolized in the liver by an enzyme called CYP 3A4. Milk thistle (or silymarin) inhibits this enzyme. This is discussed on the Memorial Sloan Kettering herbal database here
http://www.mskcc.org/cancer-care/herb/milk-thistle
This database has a lot of common herbs that you can look up interactions for. I would avoid anything that inhibits CYP3A4.

I will also look and see if my student's work in humans using a probe drug for CYP3A4 is available to the public as well.

Hope that helps,
Dr. Walko

Reply # - July 16, 2013, 10:10 PM

hain
Posts: 113

Dear Dr. Walko and Dr. West,

Thank you very much for your thoughtful replies.

After speaking to my mother regarding this matter, she feels that it may be best to stop all her naturopathic remedies in the meantime and only take the Iressa until the next follow up (in 2 weeks time). I'm hoping that stopping these agents for 2 weeks is enough to show a difference in subsequent liver enzyme levels. I'm also hoping that this is the correct decision to make in this situation.

We are also curious whether or not my mom's regular medications should be discontinued or not. My mom doesn't regularly see her family doctor so she is currently still taking her regular medications irrespective of her commencing the Iressa treatment for the past month.

Here are her current regular medications:
1) Fosavance TB 70/5600 (70mg alendronate + 140ug/5600IU cholecalciferol (Vit D3)) - Take 1 tablet, once weekly
2) Atorvastatin 10mg - Take 1 tablet, once daily (been taking it on and off; very irregularly)
3) Amlodipine 10 mg - Take 1 tablet daily (haven’t been on it for months now since her blood pressure has been stabilized, however, she takes it as needed if her blood pressure is deemed to high that same day)

Dr. Walko: Thank you for the website and the reference you provided. The website seems to offer great information regarding herbal products and will certainly serve as a valuable resource.

Best regards,
William

Reply # - July 17, 2013, 06:10 AM

dr walko
Posts: 102

William,

I cannot make any recommendations regarding continuing or discontinuing the other medications she is taking. I can say that I would not expect any clinically relevant drug interactions between Iressa and the three that you listed.

Hope that stopping the herbal products may help with the liver enzymes.

Best wishes,
Dr. Walko

Reply # - July 17, 2013, 05:56 PM

hain
Posts: 113

Dear Dr. Walko,

Your replies are very much appreciated - thank you!

I apologize if I ask too many questions, but it is because there is just so much to know and consider before making an informed health decision.

I just have another question for you (or anyone else who may know the answer). My mom has been juicing on various vegetables and fruits on and off. She will start juicing again instead of her herbal remedies as we understand that different vegetables have different important phytochemicals that are often helpful for anti-cancer purposes.

I was wondering if you could possibly comment on whether or not there are any known vegtables and/or fruits that may interfere with the Iressa's mechanism of action or side effect. It was explained to us to avoid certain foods such as: certain type of organges and pomegranate.

My mom is mainly juicing cruciferous vegetables along with beets, carrots, and apples. These cruciferous vegetables include:
- Kale
- Cauliflower
- Bok choy
- Cabbage
- Brussel sprouts
- etc.

I hope juicing vegetables won't affect her liver enzymes. If you know of any references I can use to look up these answers myself I'd be more than happy to do the research. Looking forward to hearing back from you.

Best regards,
William

Reply # - July 17, 2013, 11:20 PM

hain
Posts: 113

Dear Dr. West,

Thank you for your reply.

As you have pointed out, I forgot to mention grapefruit and star fruit. I found an interesting study that tested the effects of different tropical fruits on inhibition of CYP3A4 and it seems that papaya fruit was shown to be comparable to grapefruit in its inhibitory activity of CYP3A4. Although the fruit and the leaf extract are two different parts, they both are believed to contain similar anti-cancer properties. I'm glad we decided to stop the papaya leaf extract tea.

Here's the article if you are interested: http://www.ncbi.nlm.nih.gov/pubmed/15155547?dopt=abstractplus

Best regards,
William

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