Is Pulsed Dose Tarceva Still An Option? - 1251316

njliu
Posts:142

Dear Friends at GRACE,
Here we are at roughly a one year anniversary of diagnosis/Iressa Treatment and living asymptomatic normal life. However, meeting with our Oncologist today raised the alarm.
Update from the latest scan: PET/CT Scan clear. Brain MRI reveals subcentimeter enhancing at (1) Right Frontal Cortex 4x5x7mm; (2) Left Parietal Subcortical 6x6mm; (3) Right Substantia Nigra 3mm; and (4) Suggestion of Leptomeningeal Enhancement seen within the Cerebellar Folia.
The doctor is referring us to see a Radiation Therapist for the options of WBR or SRS. I have a few questions here and would appreciate some input from GRACE community.
1. Does the state of disease as briefly described above warrant an immediate radiation or is still reasonable to just place under Close Watch with another MRI 8 weeks down the road to assess the rate of progression before taking any action?
2. While WBR or SRS are the standard treatment options, would Pulse Dose Tarceva be another reasonable choice? (She is on half-dose Iressa now)
3. Out of all the above MRI observation, is the Leptomeningeal Enhancement of the most concern?
Thank you in advance, and wishing all a Joyous Holiday Season.
NJ

Forums
Full Archive

Reply # - December 13, 2012, 03:15 AM

certain spring
Posts: 762

Dear NJ, I am sorry you and your wife are having to deal with this news. I am sure Janine will call in a doctor to respond, and I'm probably not the person you want to hear from.
The reason I'm posting is just to state the obvious: that "leptomeningeal enhancement" seen on a scan is not the same as "leptomeningeal disease" diagnosed in a patient. MRIs show a lot of things - if you scan a group of healthy adults, a proportion will show apparent brain abnormalities - and what they show changes over time. Without going into undue detail, I've had experience of an MRI scan that showed something very worrying, yet by the next quarter it had mysteriously "resolved". So please don't assume the worst, even though I quite understand why you will want to think about it and plan for it.

Reply # - December 13, 2012, 08:58 AM

catdander
Posts:

NJ, I'm so sorry you and your wife are going through this worry. Hopefully the lepto scare will turn out to be nothing. I've noted on this forum that an mri concern of lepto turns out negative.
I will contact a doctor to answer your questions.

Certain Spring, we're always interested in your input to don't feel you should hold back.

Janine
forum moderator

Reply # - December 13, 2012, 04:34 PM

Dr West
Posts: 4735

I'm very sorry to hear about those findings, which unfortunately do sound very concerning for meningeal carcinomatosis.

I would say that the value of whole brain radiation (WBR) is somewhat between underwhelming and negligible in meningeal carcinomatosis, and the value of stereotactic radiosurgery (SRS) is even less established and hard to even envision that it could/would be helpful. My personal view is that the best argument for WBR is the "don't just stand there -- do something!" compulsion, but the reason it's not a standard treatment here is that it's not just my view: there isn't evidence that it works, and everyone's been tempted to try it, so it's not untested either. And SRS just doesn't make any sense for a problem where the cancer cells can circulate anywhere the cerebro-spinal fluid (CSF) goes, which is throughout the central nervous system (CNS) -- especially when you're already talking about multiple visible lesions. It's the same reason focal radiation makes no sense when cancer cells are circulating through the bloodstream. The best thing I could say about SRS is that it hasn't been [i]proven[/i] to be useless -- there's just very good reason to presume it should be.

As for pulsed Tarceva (erlotinib), it's not established/proven, but there are several cases in which it has been effective, particularly (maybe only) in patients with an activating EGFR mutation. Some doctors may rebuff doing a treatment that has just anecdotal reports supporting it, but you end up giving the same amount of Tarceva over the same time (600 mg every 4 days vs 150 mg every day), so it's not that you need to write a prescription for more than a standard dose. And an insurer doesn't necessarily know or care about the schedule that drugs are being taken if they're paying for a standard amount in a month. And as I've probably already betrayed by now, it's my preferred approach in this setting.

Good luck.

-Dr. West

Reply # - December 13, 2012, 05:27 PM

cards7up
Posts: 636

Just wondering if they've mentioned doing a spinal tap? Though not always conclusive, many times it is in diagnosing meningeal carcinomatosis. Wishing you all the best. Take care, Judy

Reply # - December 13, 2012, 09:34 PM

njliu
Posts: 142

Dear Dr. West, thank you very much for always be there for us in time of distress. Your expert's opinion means a lot to shed light on the challenges ahead and the assessment of available options.
Dear Certain Spring, Janine and Judy, thank you for sharing. Your words, which are of course helpful and welcome, are at least comforting that we are not alone in dealing with this dreadful disease. Yes, we are looking at doing a Lumbar puncture to draw some spinal fluid for test. The question is what difference in course of action if the result is positive, negative or uncertain? We are seeing the Radiation Therapist later today and I shall update as and when there are new development.
NJ

Reply # - December 14, 2012, 07:37 AM

njliu
Posts: 142

Here is an update: We are going to have an MRI on spine tomorrow in order to see if that can confirm the presence of Leptomeningeal Carcinomatosis. Radiation Therapist is suggesting WBR. However, I am inclined towards trying out Pulsed Tarceva for 2 weeks, then rescan to check response. If it is negative, then order WBR. Is this plan reasonable?
NJ

Reply # - December 14, 2012, 09:25 AM

double trouble
Posts: 573

Dear NJ, I just wanted to let you know that you will be in my heart and thoughts. You have many friends here so there will be a lot of prayer and positive energy coming your way.

Debra

Reply # - December 14, 2012, 01:28 PM

catdander
Posts:

I hope you won't spend time on hindsight. It's only harmful, you'll never have the answer, and it isn't standard of care nor proven.

I'll keep you in my thoughts while you hold your nerve and wait for the answers. If it is decided lepto is the most probable dx you have a plan that has shown promise. If not there is wbr that has proven results.

I wish I could help more,
Janine

Reply # - December 14, 2012, 09:53 PM

Dr West
Posts: 4735

I agree completely with Janine on the question of prophylactic cranial irradiation. It absolutely isn't standard treatment, and it's always tempting to look back with the benefit of hindsight and identify ways to have possibly changed the course. But you only know what is knowable at the time, and it's not fair nor productive to torture yourself with "what if" questions that are only sensible with the benefit of hindsight.

My only comment about delaying treatments is that leptomeningeal carcinomatosis is sometimes associated with a rather rapid decline. However, I don't think that WBR is effective enough for leptomeningeal carcinomatosis that it's something that would be painful to postpone. In fact, in someone with an EGFR mutation and leptomeningeal carcinomatosis, pulsed Tarceva may well be the stronger option.

-Dr. West

Reply # - December 15, 2012, 02:35 PM

njliu
Posts: 142

While reading "Brain Metastasis in Lung Cancer" by Dr. Loiselle on GRACE here, I noticed that he did not touch on Leptomeningeal Carcinomatosis. Does this mean Leptomeningeal Carcinomatosis is a distinct complication that departs from general brain metastasis and the established wisdom on brain metastasis does not apply to meningeal complication?

NJ

Reply # - December 15, 2012, 03:07 PM

catdander
Posts:

That's right. It's an issue all it's own and unfortunately doesn't have very good treatment options. That's why the pulsed tarceva is suggested as an option that many oncologists have tried and seen promising results but it hasn't been properly vetted in trials. I'm so sorry you and your wife are dealing with this.

There are many discussions about it in the forums. You may need to log off before our search feature works depending on your browser.

Keeping you both in my thoughts,
Janine

Reply # - December 15, 2012, 03:38 PM

certain spring
Posts: 762

Yes - I think there has been some confusion. Leptomeningeal carcinomatosis refers to cancer cells in the lining (meningeal fluid) of the brain, not in the brain itself. Pulsed tarceva is an experimental treatment for leptomeningeal disease, not for brain mets. WBR is a treatment for brain mets, not for leptomeningeal disease.
NJ, it is probably futile to say this but I hope you and your wife will not torture yourselves with worry until you have a definite diagnosis.

Reply # - December 15, 2012, 04:41 PM

Dr West
Posts: 4735

Just as a small point of clarification, WBR is certainly an approach that is tried in some people with leptomeningeal carcinomatosis, but it's not a therapy that has enjoyed clear success in that setting, in contrast with its indication in treatment of multifocal brain metastases.

-Dr. West

Reply # - December 15, 2012, 11:09 PM

njliu
Posts: 142

Thanks to all the sharing and concerns.
May I conclude that Pulsed Tarceva could have efficacy on Brain Mets and if it can activate response on Leptomeningeal Carcinomatosis, it is likely to work on multifocal brain mets too?
NJ

Reply # - December 16, 2012, 12:27 AM

Jazz
Posts: 279

Dear NJ,
My heart goes out to you and your wife as you face this new threat. I'm glad she is at least asymptomatic and has reached a year anniversary. May this state continue, despite what you are now facing.

As you might have read in some of Dr. Weiss' comments on previous posts regarding Leptomeningeal C., lumbar punctures (even multiple attempts) can be inconclusive in confirming LC. This certainly doesn't make your job easier but I thought I'd mention that. I imagine you've read this post but just for convenience, here's Dr. Weiss' post on pulsed Tarceva in action:
http://cancergrace.org/lung/2011/11/03/pulsed-tarceva-for-lmc/

I don't know where you're located but I truly hope you can obtain Tarceva and get guidance and support for the pulsed regimen if indeed LC is confirmed. However I also hope and wish for the best for your wife (--it is my fervent wish that all of this would just go away, that pharma companies would truly find a cure and not just greater profits---)

Sending strength,
Jazz

Reply # - December 16, 2012, 09:01 AM

Dr West
Posts: 4735

NJ,

It's not well studied, but yes, I'd presume that pulsed Tarceva would also be a useful approach for treating brain metastases, at least in patients whose cancer is sensitive to Tarceva. The rationale is that this schedule should be a means of getting more effective dosing of the drug into the CNS.

-Dr. West

Reply # - December 17, 2012, 05:19 AM

njliu
Posts: 142

Update: Spinal MRI shows no definite evidence of metastatic involvement.
The options being considered now are:
Treat the multifocal brain mets with WBRT as if there is no leptomeningeal disease and keep Pulsed Tarceva in the tool box for later use? or
Treat with Pulsed Tarseva as if there is confirmed leptomeningeal disease while keeping WBRT in the tool box for later use?, or
Do none of the above, but revert back to full dose of Iressa (or switch to full dose Tarceva) and do a repeat Brain MRI in 4 weeks?
Any opinion would be very much appreciated.
NJ

Reply # - December 17, 2012, 07:33 AM

Dr West
Posts: 4735

This is in the range of making a medical recommendation for someone who isn't my patient. There is no right answer here, but I feel that I've conveyed my priorities among the options elsewhere. I wish you and her good luck and hope things go well.

-Dr. West

Reply # - December 17, 2012, 12:36 PM

njliu
Posts: 142

Dear Dr. West, sorry for asking something that is not appropriate. My wife and I are deeply thankful to you. You have been most helpful with prompt and generous input. GRACE has been a great companion to us during this difficult journey.
NJ

Reply # - December 17, 2012, 03:37 PM

certain spring
Posts: 762

NJ, I'm glad to hear this news. I also haven't seen you mention any symptoms that are suggestive of leptomeningeal disease. I hope your wife's doctors were mistaken in their suspicion.

Reply # - December 18, 2012, 01:38 PM

certain spring
Posts: 762

The brain mets were found during the diagnostic process on an MRI scan. I'd had headaches and - I now realise - loss of concentration for some months. But coughing up blood was the presenting symptom, not headaches.
On the leptomeningeal issue, I would like to share my experience. About a year ago (and more than a year after I'd had WBR), the oncologist said there was evidence of "leptomeningeal enhancement" on an MRI scan. She just dropped it into the middle of the conversation, saying they wouldn't do a lumbar puncture because she didn't want to put me through that.
There followed a bad few months. The only reason I was able to hold my nerve was that I had just finished my PhD, and it seemed unlikely - based on what I had gleaned from GRACE - that if I really did have leptomeningeal carcinomatosis I would have been capable of functioning at that level. I also knew from my EGFR saga that doctors can occasionally get things wrong. Sure enough, at the next scan there was "no evidence of pathological enhancement". No one ever explained or apologised, and the whole episode damaged my trust in my oncologist.
I offer this not as a comparison with your wife's situation, but to show that this very serious condition can be misdiagnosed, and scans misinterpreted. This is a sensitive issue for me, and I hope anyone responding will bear that in mind.

Reply # - December 18, 2012, 07:27 PM

njliu
Posts: 142

Dear Dr. Certain Spring, if I may greet you that way, thanks a million for promptly answering and sharing generously more. Your sharing of your Leptomeningeal scare lights up the Christmas in our home. It does absolutely give us hope as my wife has so far not experienced any neurological symptom. We plan to deal with the Brain Mets with WBR and increase the Iressa (maybe replace with Tarceva) to full standard dose, to both increase the potent of the drug in preventing any progression as well as to get ready for a pulsed dose if a future scan were to confirm progression in Leptomeningeal.
Thanks to GRACE for helping us cope with this rough journey.
NJ

Reply # - December 19, 2012, 12:15 PM

certain spring
Posts: 762

If anything I've said has helped, I shall be very glad.
WBR was tough, but as you know already I have found it to be worthwhile. There is also some evidence that people with the EGFR mutation who develop brain mets have better outcomes. Whether this is right or not, a paper on this subject cheered me up a bit. Dr Sequist is one of the co-authors (Eichler et al, "EGFR mutation status and survival after diagnosis of brain metastasis in NSCLC", Neuro-Oncology 12 (11): 1193-1199 (2010).

Reply # - January 5, 2013, 06:14 PM

njliu
Posts: 142

Hi Certain Spring, thanks for your thoughtfulness in following up and best wishes to you in this New Year too. My wife is doing fine after 6 sessions of WBR with 4 more to go. Knowing that the delayed side effects could set in, we are approaching each day with heightened apprehension. We eagerly reverted back to full dose Iressa. The next scan is scheduled 12 weeks down the road as we were told that is the required time frame for WBR to fully work.
NJ

Reply # - March 8, 2013, 11:47 PM

njliu
Posts: 142

Hi Craig, that is so nice of you to share this piece of information. Thank you very much. As an update, my wife is doing fine without any of the feared symptoms of leptomeningeal carcinomatosis as well as those side effects of WBR while continuing with full dose Iressa. She will undergo both PET Scan and Brain MRI next week.

Reply # - March 14, 2013, 03:33 AM

njliu
Posts: 142

9 weeks after completing 10-session WBR to deal with 4 sub centimeter brain mets and leptomeningeal enhancements, a follow up Brain MRI shows rather perplexing result (while PET is stable):-
1. The 4 original mets remain visible, with slight shrinkage. ( aren't they supposed to be totally eradicated?)
2. A new met is observed. ( how can one pop up right after WBR? So soon?)
3. No visualization of leptomeningeal enhancements. (isn't this supposed to be less likely to disappear?)
Although anything can happen, the treating doctor seems to be perplexed too and I would like to ask how uncommon is this development and if there is any rational explanation to these changes? Thank you.
NJ

Reply # - March 14, 2013, 10:31 AM

catdander
Posts:

Hi NJ, I'm so glad to hear the PET is stable. Scanning after radiation very well can remain difficult to read especially within the 3 months following. It very possible that the cancer is gone and inflammation or scar tissue remain. Only time will tell.

The lepto concern was only that, concerning through MRI. Only cells in hand from her spinal fluid can definitely diagnose that. If your wife isn't showing symptoms of lepto and scans have returned to normal then it was very likely not lepto in the first place.

I will ask a doctor to respond because you said your doctor was perplexed and I may have missed something. I've not thankfully had 1st hand experience with brain mets.

All Best,
Janine
forum moderator

Reply # - March 14, 2013, 11:26 AM

drevans
Posts: 6

Wonderful news that the PET is stable!
As far as your questions on the MRI, first know that MRi's can be tricky...
1) it is not unusual that the mets have not been totally irradicated but have only shrunk, particularly on scanning done so soon after radiation (they may continue to improve, but as long as they are not getting bigger, that is a good thing!)
2) possible new met: this would be somewhat unusual though not impossible this soon after whole brain radiation, particularly given everything else better. I would ask, a) is it really a met? (would be more clear if this is larger and with edema, but can be very hard to tell whether or not a small thing on scan is truly a met), b) is it really new? How soon was the last scan prior to the whole brain radiation? Could be this popped up since the prior scan but before the radiation so may not truly be getting worse. Regardless, unless this is sizeable and felt likely to be symptomatic soon, best strategy likely to get follow up imaing. If it truly is a growing brain met, then stereotactic treatment may be beneficial
3) Leptomeningeal enhancement is, in my experience, a pretty nonspecific finding meaning that it may be leptomeningeal cancer but also may not be...if it is, then it certainly could improve after radiation, but in general I don't put too much stock in this finding when it appears on MRI or disappears.

Hope this helps!

Reply # - March 14, 2013, 12:30 PM

Dr West
Posts: 4735

I agree with everything Dr. Evans said above, and I just wanted to underscore her point about the leptomeningeal enhancement being a "soft call" that quite nonspecific. I also don't take this as a definitive finding at all.

-Dr. West

Reply # - March 14, 2013, 02:31 PM

njliu
Posts: 142

Dear Janine, Dr. Evans and Dr. West, as always, you are great. Your prompt and clear insights lighten up our understanding to the matter and is greatly appreciated. Thank you very much. Agree to adopt the strategy of follow up imaging, perhaps 6 weeks down. Leptomeningeal finding has been a heavy bearing on us. We are happy and relieved to learn that it is rather non specific and must be confirmed with lumbar puncture and related symptoms.
NJ

Reply # - April 20, 2013, 02:22 PM

njliu
Posts: 142

Again feeling thankful to GRACE. Armed with the little but critical knowledge gathered here, we were able to deal (without excessive anxiety) with the discovery of one "new" mets from the post (9 weeks) WBR scan, turning down the treating doctor's strong suggestion to perform immediate SRS, instead waiting out for a repeat MRI at 13 weeks post WBR. I am pleased to share that we had good surprise. The "new" mets shrunk from 10 mm to 8 mm which secures the verdict of no SRS required. This outcome suggests that the WBR was still working, however the puzzling fact is why this mets did not show up at the pre (10 days) WBR scan. Could this be something that grew from nothing to 10 mm in 10 days prior to WBR? Or it is more likely to have been there but not detected by the scan due to limitation of technology (like it falls between the crack of slices of scan pictures? In the meantime, we are just glad that all the mets are decreasing in size and prominence.
NJ

Reply # - April 20, 2013, 05:56 PM

Dr West
Posts: 4735

I can't explain that. I wouldn't expect an MRI scan done 10 days earlier would show nothing, followed by an MRI showing new lesions up to 10 mm (I could believe 2-4 mm, but not 10 mm). Please let us know how things go, and if she's having new or worrisome neurologic symptoms, that'd be a reason to intervene sooner rather than later.

Good luck.

-Dr. West

Reply # - December 19, 2013, 05:00 PM

mga2013
Posts: 3

Hello,

I have a question about the pulsatile dose of tarceva and its interactions with herbal supplements. A family member of mine, diagnosed with Leptomeningeal Carcinoma, have started taking 1500 mg tarceva (that is 10 pills of 150mg) once a week. There are no major side effects, except for some diarrhea and weakness. However, recently, we are considering giving our family member a herbal medicine called "curcuma" also known as Tumeric. It has been shown to have apoptotic effects as well as to help prevent the growth of different cancer cells, including brain tumors. However, I dont know if Tumeric/curcuma is recommended to a patient taking such a high dose of tarceva. If anyone has any experience or ideas whether is safe/recommended to give 1500mg of tarceva along with tumeric/curcuma supplements, It will be greatly appreciated. Thank you very much for taking time to read this entry!

Reply # - December 19, 2013, 08:59 PM

Dr West
Posts: 4735

There has never been any study of this, and because there is really no established role for either curcumin/turmeric or pulsed dose Tarceva, there is no way to make any kind of recommendation about taking them together or not.

You can have an attitude that you have nothing to lose by just trying everything, but responses to pulsed Tarceva without turmeric have certainly been described, so I don't know that I'd just start throwing everything at the cancer all at once when you've got at least one treatment that many experts would favor trying. I don't know of any cancer experts who are recommending turmeric in any situation, though I can certainly understand the temptation to pull out all of the stops and try everything. I am just less inclined to follow that mindset if you have at least one option that many people would converge in recommending.

Good luck.

-Dr. West

Reply # - December 19, 2013, 10:25 PM

bobradinsky
Posts: 144

MGA

LMC, as you have probably researched, is almost always terminal and the survival rate is normally 4-6 months. in my wife's case she started pulse dosing 1500 mg and eventually increased the dosage to 1,800 mg (900 mg twice weekly). She survived approximately 6 months. The only studies I could find were anecdotal since there is no momentum out there to do clinical trials on such a small population since it is not extremely common, but certainly not rare.

I think most oncologists would try to discourage you from combining other agents with Tarceva as it could possibly reduce the effectiveness of the Tarceva or by some chance the combination could increase the toxicity. I considered having my wife try some alternative (non FDA approved) medications but chose not to. I lost my wife anyway. You're kind of on your own here. I could not blame or dissuade you from trying an alternative cure. Best of luck whichever way you go and please keep us posted. Bob

Reply # - December 20, 2013, 11:54 AM

mga2013
Posts: 3

Thank you very much Dr West for your logic and reasonable explanation. I completely agree with you and I decided that we will keep the one clinically accepted and studied option, which is the pulsatile dose of Tarceva. Also, I was able to find out that Tumeric is a CYP3A4 inhibitor, and Tarceva is metabolized by this hepatic enzyme. So, We will stay with Tarceva for the time being, and maybe try Tumeric in the future in case Tarceva does not work. Dr West, Thank you for your understanding and for sharing your knowledge and experience.

Bobradinsky, thank you for sharing your story! LCM has poor prognosis as you know, and we are also trying Tarceva as our last resource mainly for quality of life. As tempting as all these herbal supplements sound like, we dont know how they are going to interact with newly developed pharmaceuticals. For that reason, we are also opting to wait before using Tumeric alongside with Tarceva. Thank you for your support!

Previous PostNext Post