do TKI's inhibit carboplatin / Alimta if taken together ?

Portal Forums Lung/Thoracic Cancer EGFR Inhibitors do TKI's inhibit carboplatin / Alimta if taken together ?

This topic contains 7 replies, has 3 voices, and was last updated by  kempten 1 month ago.

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October 17, 2017 at 8:11 pm  #1293341    

kempten

Hello

If I keep taking Tagrisso p.o. together with Carboplatin / Alimta iv chemo, will the TKI have an inhibitory affect on the chemo?

” Most chemotherapeutic agents work to halt cell division at a certain point. The idea is to kill cells that divide rapidly, one of the main properties of cancer cells.
Cancer cells inhibited by tyrosine kinase inhibitors do not divide frequently, so they are much less sensitive to chemo agents targeting dividing cells.”

I was told I can keep taking my Tagrisso , but I’m worried it might keep the chemo from working as it should by putting the cancer cells into a kind of ” hibernation ” and making them less vulnerable to being killed off ?

some chemotherapeutic agents such as platinum-compounds are cell cycle NON-specific. does this means that there should be no mutual inhibitory effect with TKI’s ?

thank you for your answer

Kempten

October 18, 2017 at 4:55 pm  #1293345    
JimC Forum Moderator
JimC Forum Moderator

Hi Kempten,

The question of antagonism between a TKI and chemo is one which has never been fully answered. The argument in favor of combining the two regimens is that lung cancer is not always heterogeneous; some cells may not have developed resistance to the TKI, so the TKI may continue to effectively control that portion of the cancer, while the resistant cells quickly multiply and are treated effectively by the chemo. Dr. West wrote about the issue quite a while ago, but some of the basic concepts remain valid. Of course this was before the advent of third-generation EGFR TKIs.

When the issue first arose, some oncologists withheld the TKI for a day or two before or after each chemo infusion, in order to avoid a negative interaction. I haven’t heard much about that concept of pharmacodynamic separation recently, and it’s not clear that it’s necessary to prevent such interactions.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

October 18, 2017 at 8:43 pm  #1293347    

kempten

thank you Jim

My fear is that we will kill off the resistant fast dividing cells only , leaving the cells that are still responding to the TKI in hibernation and they are then protected from the chemo .
Would it not be better to kill off both sets of cells instead of just keeping a bunch alive with a temporary chemical brake. At some point the cells that are still responding to the TKI will also become resistant This could cause a quick flare of disease after the chemo is stopped.

What about cell cycle non specific chemo compounds . Is there a difference in interaction With TKI’s ?

The fact that this question is not settled is very unsettling

How often do patients who move on from a 3rd generation TKI to iv chemo remain on their TKI ?
What is general practice if there is such a thing.

I am of course aware that I will also become resistant to the chemo or that there is a chance that the chemo might not work at all but I wished I could influence this a little by deciding weather or not dropping the TKI makes a difference in effectiveness.

Kempten

October 19, 2017 at 7:03 am  #1293348    
JimC Forum Moderator
JimC Forum Moderator

Hi kempten,

I understand your frustration; unfortunately at times there are issues that do not get fully studied. I’ll see if I can get a faculty member to respond to your questions. Hopefully there is some data to help you make a decision.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

October 19, 2017 at 7:55 am  #1293349    
JimC Forum Moderator
JimC Forum Moderator

Hi Kempten,

Dr. West has just returned from the world conference on lung cancer in Japan, but we should have a response for you tomorrow.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

October 19, 2017 at 8:03 am  #1293350    

kempten

Thank you so much Jim

I very much appreciate your continued help.

Kempten

October 22, 2017 at 10:21 pm  #1293379    
Dr West
Dr West

Kempten,

There is a gulf between what we might hypothesize and what actually happens. I would put very little stock in a theory that isn’t proven by actual evidence in real patients. That said, we actually have no studies directly testing keeping patients on a third generation EGFR inhibitor like Tagrisso (osimertinib) while giving chemo vs. just switching to chemo and leaving the EGFR inhibitor behind. However, I would say that nearly all experts are swayed by the results of a trial called IMPRESS that compared a switch from Iressa (gefitinib) to chemo upon acquired resistance to Iressa vs. continuing the Iressa with the same chemo (cisplatin/Alimta (pemetrexed)). That trial showed no benefit in outcomes for continuing Iressa, and even a strong trend toward worse survival in the arm that continued the Iressa along with starting chemo.

Based on these humbling results, most lung cancer experts are definitely disinclined to recommend continuing patients on an EGFR inhibitor or even an ALK inhibitor once significant acquired resistance to the targeted therapy has developed. I’d make an exception for a patient who develops a “flare reaction” of marked symptomatic worsening within 1-2 weeks of stopping their targeted therapy, but otherwise I favor having my patients stop their targeted therapy when starting chemo.

I hope that helps.

-Dr. West

October 23, 2017 at 12:50 pm  #1293384    

kempten

Thank you so much for your reply Dr West.

I just received the opposite advice from my Oncologist who had just joined you in Yokohama. I’m supposed to remain on the Tagrisso in the hopes it might still continue to protect the brain to a certain degree. I originally was diagnosed with 9 brain mets 2 1/2 years ago that have been controlled with Tarceva , SRT ( 3 leftover mets ) , Tagrisso and a second SRT ( one new met in the cerebellum 2 months ago ) .

The lung tumor was irradiated too. Since then the disease has progressed in the lung and we decided to move on to Carbo/Alimta

Naturally the 2 different opinions are causing me sleepless nights . I feel I’m dammed if I do , and I’m dammed if I don’t.

How do your patients fair on average with the discontinuation of their TKI and moving on to chemo?
Is there a chance the Alimta can be effective in the brain after the TKI brake has been removed ?
My first chemo is on Wednesday . When would you have me stop the Tagrisso ?
What should I ask my oncologist ?

Thanks again

Kempten

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