Tarceva maintenance therapy after chemo - 1252845

remco
Posts:14

Hello,

First of, I really like to thank all of you for this great site. It has been an enormous help for me.

My mother is diagnosed with stage IV NSCLC (adenocarcinoma). She has a metastatic brain tumor and has an EGFR positive mutation.

As first line treatment she received Iressa. Unfortunately, after some months it was discovered that the Iressa worked well on her lung tumor, but not on the brain tumor (there were new (very small) metastases and the main brain tumor grew slightly). So radiotherapy (WBRT) was tried, but it did not work; the brain tumor grew further.

So the decision was made to switch to chemotherapy: cisplatin/alimta combination (for 4 cycli). In about two weeks there will be a CT scan to see if the chemotherapy has effects.

But to get to my main question: If the chemotherapy is succesful, the idea is to use Tarceva after the chemotherapy is done (so this is called a maintenance therapy, right? (not a native english speaker)). The decision to use Tarceva instead of Iressa has been based on a very small preliminary study (6 persons) which showed that Tarceva had a higher penetration rate in the brains than Iressa had.

But now I stumbled upon an old article on this site, stating that Iressa might be DETRIMENTAL as a maintenance therapy after chemo? See: http://onctalk.com/?p=155 and http://cancergrace.org/lung/2007/07/27/challenges-for-consol-taxotere/ and http://cancergrace.org/lung/2011/01/03/adding-egfr-inhibitor-therapy-to…

I want to discuss this with our lung specialist, but did I get this right? (I am a layman) Also, I would be very interested in any additional information/insight you might be able to provide me.

Thanks a lot!

Kind regards,
Remco

Forums
Full Archive

Reply # - January 21, 2013, 05:03 AM

remco
Posts: 14

P.S. I'm also wondering what you think might be the reason Iressa does not work on the brain tumor? I'm reading the "mixed response"-articles... might it be that the brain cells do not have a EGFR mutation?

So far, the assumption of our lung specialist is that it is very likely both lung cells and brain cells have the EGFR mutation, but that Iressa does not penetrate the brain in sufficient dose for it to be effective. Is that a credible hypothesis?

Thanks.

Reply # - January 21, 2013, 09:04 AM

catdander
Posts:

Hi remco, I'm very sorry to read about your mother's problems with lung cancer. I know how terrible it must be.
I'm unsure you have a good understanding of brain mets. It is understood that chemo and tarceva and iressa do not pass through what is called the blood brain barrier (bbb), which means the drugs you're discussing would not be expected to get to and work on the brain mets. It's true that in a small portion of people it does pass through the bbb and help but it isn't know how or why and isn't given as treatment for brain mets as any kind of standard practice.

Otherwise it sounds like your mother is responding well to treatment outside the brain so that is very good. Instead of systemic treatment what you may want to read more about it particular is brain mets so you can discuss with her health care providers. You may do a search on Grace but may need to log out first depending on your browser.

Below is an blog/post by a radiologist who works closely with people with brain mets. He discusses ways in which your mom might be treated since she didn't respond to radiation.

http://cancergrace.org/lung/2011/09/11/brain-metastases-in-lung-cancer-…

I wish her very good luck moving forward,
Janine
forum moderator

Reply # - January 21, 2013, 09:50 AM

catdander
Posts:

I just came across this video blog by Dr. West from just over a month ago on the subject of brain mets. I confess I've not watched it but I bet he discusses bbb.

http://cancergrace.org/radiation/2012/12/07/video-on-systemic-rx-for-br…

OK, I just watched it and as the title suggests it is a discussion about giving the egfr inhibitor a chance to work on the brain before going on to radiation. Which is what your doctor did with iressa. It sounds as though the doctor wants to give tarceva a try which may be reasonable due to the standard dose of tarceva is thought to be higher than the standard dose of iressa comparably speaking.

I'll make sure Dr. West addresses this today. If he doesn't on his own I'll contact him.

Don't miss the additional links at the end of the blog/posts.

Reply # - January 21, 2013, 02:26 PM

Dr West
Posts: 4735

I'm sorry to hear of your mother's diagnosis and progression of brain metastases.

The situation of Iressa (gefitinib) for maintenance looking potentially detrimental is a different situation than the one your mother is facing. The setting in which it appeared harmful was in a group of unselected patients, not those with an EGFR mutation, which is a very different question. Second, the setting in which Iressa was harmful was after chemo and chest radiation for locally advanced NSCLC, a very different setting than advanced/metastatic lung cancer.

It's really unknown how well the oral EGFR inhibitors work on brain metastases in people with an EGFR mutation and known brain mets. Certainly, some people respond and respond very well in the brain. Other people respond very well outside of the brain but less well or not at all in the brain. You don't tend to see a better response in the brain than in the chest or elsewhere, but otherwise, we don't have enough information to say much more than it's arguably worth trying to hold off on brain radiation to see how a person with an EGFR mutation and brain metastases responds to an EGFR tyrosine kinase inhibitor (TKI) before reflexively going to brain radiation (which is what I discuss in the video). But if you see progression in the brain, I would move very quickly to brain radiation, as was recommended for your mother.

As for whether Tarceva (erlotinib) will be significantly more effective than Iressa, we don't have much evidence in EGFR mutation-positive patients who have received one and then another. There are certainly a few patients who respond better to Tarceva than Iressa, or who respond to Tarceva after progressing on Iressa, but the results tend to be pretty comparable in EGFR mutation-positive patients otherwise, and Iressa has a milder side effect profile.

Good luck.

-Dr. West

Reply # - January 22, 2013, 01:35 AM

remco
Posts: 14

Dr. West and Janine, thank you so much for answering my questions.

It's good to hear that the situation for potentially detrimental effects of Iressa is not comparable with my mother's situation.

And if I understand correctly, there is a (hopefully decent) chance that chemo/Tarceva will penetrate the brain. That's what we're really hoping and rooting for with all our hearts.

But if it won't work, are there then any options left? Is radiation therapy an option again (maybe a different form; stereotactic radiotherapy?), or won't that work since it didn't work last time? Are there any more experimental treatments I should look into if she progresses after Tarceva?

Thanks again!

Reply # - January 22, 2013, 06:24 AM

Dr West
Posts: 4735

Please look in the radiation section for the many posts about radiation for brain metastases, including some that cover this question. There is no well established option, but there are things to consider for individual cases.

Good luck.

-Dr. West

Reply # - January 22, 2013, 11:16 AM

certain spring
Posts: 762

remco, I'm sorry to hear about your mother. I hope that, if you go for the Tarceva, it has some effect on her brain mets. In addition, we do have some GRACE members whose brain mets seem to have responded to Alimta or other chemo combinations.
I think I am right in saying that there are depressingly few new treatments coming through for brain mets. A trial for a possible drug called GRN 1005 has just been discontinued by Geron. Best wishes.

Reply # - August 26, 2013, 05:20 AM

remco
Posts: 14

Hello all,

I wanted to follow up on the situation of my mother. Maybe it will provide insights for some, and maybe some can relate to the experiences.

After chemotherapy (which showed stable brain mets during chemo, which was an improvement), it was decided to give my mother a pulsed tarceva dose, once a week, 10 pills (150mg*10). This started in the end of may.

After three months my mother had another CT scan, which showed that the brain mets had shrunken by 20-25%. So that was a very, very good result.

However, the mondays (the day on which she takes the pills) have been very hard on her. She barely speaks, can not walk (after chemo walking became much, much harder) and just blankly stares in the distance, making it very hard to make contact with her.

But, the following days it goes much better. She can talk again, she can walk for (very) short distances and is generally much more responsive and happy. It's amazing how much difference a day can make. Seems that much of the negative effects of the pulsed dose wears off after 1-2 days.

However, the last few weeks, the sundays have been harder as well. We don't know what's causing this; seems a bit strange that it very frequently happens the day before she takes the tarceva.

Today (monday) is especially bad. She is totally non-responsive (in the past few weeks she could nod etc) and has no strength in her muscles at all. Probably a slim change, but does anyone have comparable experiences with this?

Anyhow, I wanted to give an update, because as I understand a pulsed tarceva dose is not used frequently and our experiences might prove useful for some. As far as I know, there was one other person in the Netherlands on a pulsed tarceva dose, but he had to stop because of too severe side effects.

If anyone has also experiences with pulsed tarceva treatment, please share! I would be very interested to hear your experiences.

Kind regards,
Remco

Reply # - August 26, 2013, 08:11 AM

catdander
Posts:

Remco, I'm sorry your mom is starting to have more problems with pulsed tarceva.

As you know there are very few people who have tried this treatment and fewer who have tried it for brain mets so I don't know if you'll get any clarification from personal experience. The best route would be to have your mom's doctors know about these issues so she gets the quick care she needs.

I hope she feels better soon.
Janine

Reply # - August 26, 2013, 08:44 PM

Dr West
Posts: 4735

Unfortunately, I think most people doing pulsed Tarceva for meningeal carcinomatosis have found the benefits to be disappointing short-lived and relatively modest. That's the impression I'm getting from your report, though I would love to be wrong in my interpretation and have it be better than that.

Good luck.

-Dr. West

Reply # - August 26, 2013, 11:57 PM

remco
Posts: 14

Dear Dr West,

Do you mean you think those effects on monday have to do with the carcinoma itself? I was under the impression that it was a side effect of the pulsed tarceva, because 1) it only happens on mondays when she takes the medication and afterwards recovers quickly (within 1-2 days to a condition comparable to the situation before she began taking tarceva) and 2) the metastises in her brain were reduced with 20-25% after about 2-3 months treatment.

Furtheremore, my mother does not have meningeal carcinomatosis (if I understand correctly), right? (or does a brain metastisis from lung always spread to leptomeninges?). At least I think so, because I asked our Dr to tell us what kind of tumor my mother had, and he never mentioned it.

I'm kinda worried right now...I really thought it were side effects of the tarceva and not with the tumor itself. So any further information you can give me would be much appreciated, so I can discuss it with our Dr as well (who we meet in about a week).

Kind regards,
Remco

Reply # - August 27, 2013, 01:07 AM

remco
Posts: 14

Some more info (and having read some more articles here).

I'm quite positive she does not have meningeal carcinomatosis, but "regular" brain mets. The reason for the pulsed tarceva is that she has used Iressa before, showed stable disease in her lung, but progression in her brain (she has EGFR mutation). So the thinking was that a pulsed dose tarceva might penetrate the blood-brain barrier whereas a regular dose (Iressa) does not. As said, she showed response after 2-3 months (20-25% decrease in brain mets), but we havent taken a CT since (last scan was approx 3 months ago).

Thank you all very much for the responses. I truly appreciate it.

Kind regards,
Remco

Reply # - August 27, 2013, 01:30 AM

remco
Posts: 14

Ok, now I am in doubt again. I read in another thread (http://cancergrace.org/topic/tarceva-memory-loss) that LMC does not necessarily show up in a CT scan. She does have some of the symptoms:
-memory loss/speach problems
-cognitive decline, but ONLY on days she takes the pulsed tarceva
-incontinence, but again ONLY on days she takes pulsed tarceva
-difficulty walking (but that seems not have started after she took tarceva...her problems with walking began during/after chemotherapy but have slightly deteriorated since).

I'm now starting to think I fooled myself into thinking that these were mostly side effects. I thought the walking problems were mostly due to chemo in combination with prolonged dexamethason use (now 1mg/day maintainance dose, but she has had dexamethason for about 7 months now). Memory loss was also after chemo and not deteriorated much since, and incontinence and other problems happen only on mondays (when she takes tarceva). So I thought it would be logical that it would have something to do with the tarceva instead of the tumors itself (and since last scan was very good, progression was not the first thing I thought about).

I feel quite stupid now, because when I write it down in this way, combined with the fact that sundays have become a bit worse in the last few weeks, it seems like quite a high probability that it has to do with the brain mets themselves. Which obviously worries me much more.

Should I press for another CT scan when we speak to the doktor next week? Any other things I should do?

Sorry for all the fragmented posts...just trying to put my thinking on paper; helps to make it clearer for myself as well.

Kind regards,
Remco

Reply # - August 27, 2013, 06:10 AM

Dr West
Posts: 4735

I wouldn't want you to mistakenly believe that I know exactly what to expect from pulsed Tarceva or that anyone should. I have treated about 4-5 patients over the past 5 years with this approach, which is probably about as many as most people who have used it, but that doesn't give me or anyone else a great expertise, especially since all of the patients have unique circumstances and had unique responses (or no response). I treated them on a schedule of 600 mg once every 4 days, and I have never pursued the weekly dose. As I implied above, that shouldn't mean that one schedule is right and another is wrong, just that we can't presume to know how any individual person will do.

It's appropriate to discuss these issues with her doctor, but I am absolutely not advocating that you should expect or demand a repeat scan or any other workup or change in treatment. As I said, there is no clear right answer here, and all any of us can do is the provide the best judgment we can in difficult circumstances.

Good luck.

-Dr. West

Reply # - August 27, 2013, 02:05 PM

catdander
Posts:

I don't want to seem pushy or that I'm giving advice I just want to clarify for balance in decision making. Sometimes all the treatment that is needed is focus on comfort care where anticancer treatment is more harmful than helpful. I keep this understanding in my hands every time decisions are made for my husband. And my brothers and sisters and I did too for our most dear mom when she was no longer able to do so for herself. It remains the most frightening of balances to keep but among the most important as well.
With that said, I know your mother relishes the time with her family and appreciates beyond acknowledgement the care you provide her.
Best wishes,

Reply # - August 27, 2013, 10:00 PM

bobradinsky
Posts: 144

REMCO

Just read your thread and the symptoms your Mom is experiencing are quite the same as those my wife has experienced since May this year. She was diagnosed back in Sept 2012 with NSCLC/EGFR with mets to brain, bones and liver. Besides the symptoms you describe above she also complained of headaches starting in May. She was given a spinal tap and diagnosed with leptomengenial carsinamatosis (LMC). She was initially pulse dosed with 1500 MG / week but when she started to regress we upped the dose to 900 MG twice weekly ( I don't know of any others who have pulsed this many pills). It improved her life quality for several months but recently she began to significantly decline again. She can barely walk with a walker, has overnight incontinence, speech problems and cognitive decline. She needs to be watched 24/7. Her condition waxes and wanes. She has some good days when we have conversations just like old times and by evening she resumes a blank stare and has great difficulty making herself understood.. She also has trouble swallowing so I doubt I can keep giving her Tarceva much longer. She is sleeping more and more each day. I might add that she is also taking Alimta which we started just a few months ago when we suspected the Tarceva was losing it's effect. Our next stop is Hospice which I fear is sooner rather than later.

I wish I was more computer savy so I could give you her thread, but you can find it under Adinocarsinoma Stage 4 EGFR progresses to LMD - running out of options / Brain Metastases about 2 weeks ago.

Like yourself I'm not a medical professional, but there are definitely some similarities in symptoms. I'm wondering if her symptoms are coming directly from the brain mets why she would not be a candidate for cyberknife radiation or WBR? Perhaps one of the docs or moderators can answer that.

Best of luck to your Mom, you and your family. Bob

Reply # - August 28, 2013, 12:21 AM

remco
Posts: 14

Dear Dr West,

Thanks for the comment. I will discuss all of this with her doctor, whom I have great confidence in. I will update this thread next week, when we have had the conversation.

Kind regards,
Remco

Reply # - August 28, 2013, 12:29 AM

remco
Posts: 14

Dear catdander,

You're not pushy at all and I greatly appreciate your advice. It's exactly the balance you mention which is so incredibly hard to deal with. On the one hand there's always some glimmer of hope that treatment will give her more time. I also notice that this kind of hope helps my mom through her struggles. But on the other hand the side effects are very real and can potentially harm her quality of life. It's always second guessing, but luckily our doctor is also very focussed on maintaining this balance (he focussed on it in multiple conversations we had).

Kind regards,
Remco

Reply # - August 28, 2013, 12:45 AM

remco
Posts: 14

Dear Bob,

I found your thread and I'm going to read it in a second. But it's very emotional, especially because there are so many similarities. It was a complete shock for me when I first read about your and daisy1963's situation, and I felt that I really fooled myself into thinking that it were mostly side effects of medication (because her last scan showed so much promise). But I will talk to the doctor next week, and am very interested what his opinion is.

BTW, my mom has had WBR, but it didnt help (her brain mets showed progression immediately after).

I really feel what you're going through..it must be incredibly hard. I truly hope you and your wife will be able to cope in the best way possible for the road ahead.

Reply # - September 4, 2013, 01:17 PM

remco
Posts: 14

I promised to update this thread when we've spoken to our doctor, so here goes.

After the monday last week (which was especially bad), mom recovered quite quickly and we had some very good days from wednesday on. Last monday was better than last weeks and today everything was also good.

Our doctor does not think it is likely she has LMC. His main reason is that he does not think it's compatible with the pattern we're seeing where it's especially bad on mondays, but gets (much) better a few days later. If it would be LMC, he expects more steady symptoms throughout the week. Also, no anomolies showed up on the last MRI and CT, decreasing the probability she has LMC. Can you agree with this assessment, dr West?

He does agree that it's unlikely that the symptoms are due to side-effects, because it manifests itself already on sundays and the symptoms are not really compatible with tarceva use.

He does not know what it exactly could be, but thinks in more general terms that the body is fighting a chronic, incurable disease, leading to deteriorating health, causing a range of symptoms without knowing exactly what caused what. Don't know what to make of this, because the symptoms seem pretty specific.

We are now trying to increase the dose dexamethason on sundays through tuesdays (from 1 mg to 2mg) and see if the symptoms will be more managable on those days.

He does not want to do a CT scan because it's unlikely to give much new information, it's intrusive for my mother, and the tarceva showed good results on last scan and he doesn't see the new symptoms as evidence that the tarceva has stopped working. And the fact that there is not a good option after tarceva also plays a role.

So basically he told us the same thing that has been repeated many times on this site: sometimes it's better for the patient to do nothing, although it's often the hardest choice to make (because we often want to do something just for the sake of doing something).
Comments obv very welcome

Reply # - September 4, 2013, 08:55 PM

Dr West
Posts: 4735

I agree with everything your oncologist suggested, including that less can be more, and that LMC doesn't follow a waxing and waning pattern over the course of a week. One of the issues we've covered in several threads about LMC is that it's called out on a scan so much more often than it used to be that we're suspecting it's over-called sometimes, or at least that there's so much variability in the level of suspicion about it that what is now sometimes called LMC may not resemble the LMC we saw when we had a much higher threshold to call it.

-Dr. West

Previous PostNext Post