Nonsteroidal anti-inflammatory drugs and long-term Tarceva/Iressa response - 1267181

stefabi
Posts:7

I was recently discussing the case of a very long-term Iressa patient (longer than 10 years....) who has also concurrently been taking daily Celecoxib (brand names: Celebrex, Celebra, Onsenal).

While I could find a considerable amount of research on COX-1/COX-2 inhibition in several cancer types (including NSCLC), I struggled to find any thorough study of combination therapies with EGFR-TKIs and COX2-inhibitors specifically in EGFR-mutant NSCLC.

Could you please highlight any relevant studies that I might have missed?

Lacking any specific study, is there any sort of anecdotal evidence of longer-term Tarceva/Iressa response and use of NSAIDs and/or specifically COX2-inhibitors?

Thank you!

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Reply # - November 16, 2014, 10:23 AM

stefabi
Posts: 7

Thanks for your quick reply Jim.

I had already seen the study you mention. It is however irrelevant because it was done on an unselected population of 31 patients.

I am looking for studies re combination therapies with EGFR-TKIs and COX2-inhibitors specifically in EGFR-mutant NSCLC.

My eventual goal is to understand whether there is any evidence of longer Tarceva/Iressa response in EGFR-mutant NSCLC patients who have also been taking NSAIDs and/or specifically COX2-inhibitors drugs over over a 'long time'.

Reply # - November 16, 2014, 11:02 AM

Dr West
Posts: 4735

To my knowledge, this topic has lost steam, probably because earlier work hasn't panned out. I don't know of anyone looking at this question today, whether in a broad population or in EGFR mutation-positive patients.

-Dr. West

Reply # - November 16, 2014, 11:09 AM

stefabi
Posts: 7

Ok thx. I will then try to find some anecdotal answers from long-term Iressa/Tarceva responders in the patients community

Reply # - November 18, 2014, 01:39 AM

loftus
Posts: 11

stefabi,

After 26 months on Tarceva my wife may be progressing clinically, we will find out next week. But I have been looking at adjuncts like NSAids, among others, hoping for something easy to tolerate. Unfortunately, there don't appear to be any that have unequivocally proven valuable.

Then about a month ago, a paper showed that Lapatinib, a TKI, given at the beginning of their (day-time) rest period considerably slowed the rate of growth of EGFR dependant tumours in mice:

http://www.nature.com/ncomms/2014/141003/ncomms6073/full/ncomms6073.html

Big claims have been made for chronotherapy such as this, but a paper in Nature Communications including a plausible mechanistic explanation was encouraging, so I looked further.

I found a paper showing a similar effect in mice - about 50% reduction in tumour growth rate by dosing with Imatinib (another TKI) - with 3 different types of tumour - at the end of their active period:

http://www.sciencedirect.com/science/article/pii/S0006295206004941

I can't find any studies of the time of day when the TKI is taken in humans, but the logic seems strong enough that my wife is considering taking her Tarceva at the end of the day, not in the morning - depends on the oncologist's views (there may be something we don't know about). It seems simple enough, with a big possible upside and (probably) little downside.

You may want to consider this,

best regards, Alex

Reply # - November 18, 2014, 10:48 AM

stefabi
Posts: 7

Dear Alex.
Many many thanks for your reply.

I have seen the same studies regarding time of pill in-take and inquired with my wife's oncologist. He is not opposed to switching to late evening and we might start this week.

Regarding NSAIDs I have just reached out directly to a few Iressa/Tarceva long-term responders on Inspire and await their kind feedback...

Will keep you posted. Best hopes for next week!

S.

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