Question to Percy about Celebrex
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Hi, Eli,
The Funny thing is that I do enjoy your challenge and questions. If you are younger,you should study medicine .Well , it still not too late.You are good at details and analytical thinking. The answer to the first question is I am in the medical field also.You are right that aspirin has the ability to inhibit both cox-1 and cox-2 enzymes,I misunderstood that you meant aspirin is a HALF COX-2 inhibitor which does not exist. Indeed the correct pharmacologic category for aspirin is SALICYLATE , it processes NSAID properties but neither is a cox-1 or cox2 inhibitor or a NSAID and that is why I said aspirin is a different class by itself.
I agree with you it is not unreasonable that aspirin may be of benefit to patient of CCA with cox-2 positive disease but be sure to watch its S.E.
If you read my previous message, # 3 on my reply, if needed , patient can still use aspirin(81mg) while on chemo .
Again,thanks for the conversation.
God bless.Hi Percy,
Thank you for your detailed response. I will reply point by point.
PCL1029 wrote:1. I am on Celebrex 400mg BID for almost 2 years for the reason as you said. “I googled “cholangiocarcinoma COX-2″. I found a few studies that suggest that COX-2 is overexpressed/upregulated in CC.”My biomarkers report indicated I am overexpressed on the biomarker PTGS2 and thus ovrexpressed on Cox-2, that is why I still take the Celebrax even it does not seem to help my recurrence.
My understanding is that:
(a) you started Celebrex after your first resection
(b) you did your biomarkers report after your second resectionIn other words, you were able to obtain Celebrex prescription without the benefit of biomarkers report.
I wonder who wrote your prescription. Your surgeon? Oncologist? Family doctor?
I also wonder how you managed to sell Celebrex idea to them. Without biomarkers report, the evidence to support Celebrex use in CC is not that strong.
PCL1029 wrote:2. Your quote– “The result that I found the most intriguing: patients who started taking low-dose aspirin after they got diagnosed had a better survival rate than patients who didn’t take aspirin, but only if their colon cancer was COX-2 positive. This finding makes intuitive sense. Aspirin is a COX-1/2 inhibitor.” I presumed you are talking about the use of aspirin in CCA patient situation only and NOT other diseases.
Aspirin is an ” NASID’ and NOT 1/2 or whole cox-2 inhibitor. it is a different class of anti-inflammatory agent. No sorry,Eli,your find does not make sense, but a good assumption even though it is incorrect.You are right that Aspirin is an NSAID. Non-steroidal anti-inflammatory drug. If you look at the mechanism of Aspirin action, you will find that it inhibits COX-1 and COX-2 enzymes. It’s easy to verify. Just take a look at Aspirin page on Wikipedia, or google “aspirin COX-1 COX-2”.
The suppression of COX-1 is responsible for the nasty side-effect. Aspirin causes GI irritation and bleeding in some people. To overcome this side-effect, scientists developed COX-2 selective inhibitors such as Celebrex and Vioxx. BTW, these drugs are NSAIDs too.
Back to the colon cancer study that I linked in my original post. I found a good summary of the study on MedScape:
Colorectal Cancer Patients Taking Aspirin Live Longer
http://www.medscape.com/viewarticle/707279MedScape wrote:Strongest Association With High COX-2 Expression
The inverse association between aspirin use and a lower risk for colorectal-cancer-specific mortality appeared to be strongest among individuals with primary tumors that overexpressed COX-2, compared with those with weak or absent expression (HR, 0.39 [95% CI, 0.20 – 0.76] vs 1.22 [95% CI, 0.36 – 4.18]).
It is possible that other COX-2 inhibitors might have a similar effect, explained Dr. Chan. “The effect seems to be related to the inhibition of COX-2, and that mechanism is shared, so it is possible that celecoxib might have a similar benefit, although we don’t know if it will be of the same magnitude,” he said. “It has been shown to prevent precancerous polyps, so there are reasons to believe that impact on survival might be similar to aspirin.”
But for both agents, the risk for adverse events has to be considered. Aspirin is associated with gastrointestinal irritation and bleeding, and although COX-2 inhibitors, such as rofecoxib and celecoxib, have less gastrointestinal toxicity than aspirin, they have been associated with cardiovascular toxicity, Dr. Chan pointed out.
“Our study provides a compelling rationale [with which] to understand how these agents work and to develop medications that have anticancer properties but fewer side effects,” he added.
New Biomarker?
An accompanying editorial hones in on the COX-2 finding.
“The specificity of the response of colorectal cancers to aspirin for patients in whom tumors overexpressed COX-2 suggests that this potential future treatment comes with its own ready-made predictive biomarker,” writes editorialist Alfred I. Neugut, MD, PhD, professor of medicine and epidemiology at Columbia University in New York City.
In the near future, COX-2 expression may become “a standard predictive marker and aspirin may become standard adjuvant therapy in the management of colorectal cancer,” he suggests.
(red font mine)
Will aspirin show the same benefit in COX-2 positive CC as it did in COX-2 positive colon cancer? We don’t know for sure.
Is it unreasonable to say that aspirin *might* be of benefit to CC patients with COX-2 positive disease? I don’t think it’s unreasonable at all.
PCL1029 wrote:4. Your quote–“Putting two and two together, it’s seems logical to come up with a theory that low-dose aspirin might be of benefit to some CC patients.”I do not think so ;Aspirin will affect the platelet count and that is no good if patients are on chemotherapy.
Sorry, some sloppy writing on my part. I am fully aware that patients undergoing chemo MUST NOT take aspirin. We have information sheets about 5-FU, gemcitabine and cisplatin. They all warn against aspirin use during chemo.
What I meant to say is that low-dose aspirin might benefit CC patients in remission (and thus not on chemotherapy), who also happen to have COX-2 positive disease.
Wishing you the best,
EliHi,Eli
I found this from my own post;and it may be of interest to usi Celebrex.From Annals of Oncology
A recent study has concluded that using celecoxib (Celebrex, Pfizer) with capecitabine-based therapy can reduce the incidence of hand-foot syndrome (HFS) (Ann Oncol 2011 Sept 22 Epub ahead of print, PMID: 21940785).
God bless.
Hi,Eli,
1. I am on Celebrex 400mg BID for almost 2 years for the reason as you said.”I googled “colangiocarcinoma COX-2″. I found a few studies that suggest that COX-2 is overexpressed/upregulated in CC.”
My biomarkers report indicated I am overexpressed on the biomarker PTGS2 and thus ovrexpressed on Cox-2, that is why I still take the Celebrax even it does not seem to help my recurrence.But I am cutting the dose down to 400mg daily due to the cardiovascular side effect such as stroke MI CVA etc.that may incur after long term using of Cerebrex(mpore than 2 years)
Strange or not the liver is part of the extension of our GI system from the rectum;Cox-2 inhibitor like Cerebrax is indicated for familial adenomatous polyposis( one study indicated a 28% reduction of rectal polyps.) ApprovaL for non-familial adenomatos polyps is still awaited eariler this year. and for that reason,about 10 years ago COX-2 inhibitors are part of the research for CCA too partly due the human physiology and biology.
2. Your quote– “The result that I found the most intriguing: patients who started taking low-dose aspirin after they got diagnosed had a better survival rate than patients who didn’t take aspirin, but only if their colon cancer was COX-2 positive. This finding makes intuitive sense. Aspirin is a COX-1/2 inhibitor.” I presumed you are talking about the use of aspirin in CCA patient situation only and NOT other diseases.
Aspirin is an ” NASID’ and NOT 1/2 or whole cox-2 inhibitor. it is a different class of anti-inflammatory agent. No sorry,Eli,your find does not make sense,
but a good assumption even though it is incorrect.3. In case patient has to take a low-dose aspirin(81mg ) for prevention of cardiovascular diseases or for their existing heart condition, and need to take n NASID like Ibuproben (Advil,Motrin,Naprosyn,aspirin), take with a proton pump inhibitors like protonix (generic available) once a day before meal may be necessary to alleviate the risk treated by aspirin alone.(ie: GI bleeding,acid reflux ). I take protonix 40 mg daily before breakfast with my Celebrex for acid reflux- a chronic condition for me and it may be a risk factor for CCA if associated with H.Pylori.
4. Your quote–“Putting two and two together, it’s seems logical to come up with a theory that low-dose aspirin might be of benefit to some CC patients.”
I do not think so ;Aspirin will affect the platelet count and that is no good if patients are on chemotherapy. If there is no inflammation involved,and just want something for mild analgesia, Acetaminophen(Tylenol 500mg-650mg) will be a better choice but should not take more than 6-8 tablet/day or 3-4gm maxium/day due to adverse reaction to liver.
God bless.Hi Percy,
I read a post of yours where you mentioned that you take (or took?) Celebrex. I wonder why is that. Celebrex is a COX-2 inhibitor. Are you taking it because you know that COX-2 stimulates CC growth? Or some other reason? (if it’s the latter, no need to elaborate).
I will explain where I’m coming from with my question.
This medical study got a lot of play in the popular press:
Aspirin and the Risk of Colorectal Cancer in Relation to the Expression of COX-2
http://www.nejm.org/doi/full/10.1056/NEJMoa067208The result that I found the most intriguing: patients who started taking low-dose aspirin after they got diagnosed had a better survival rate than patients who didn’t take aspirin, but only if their colon cancer was COX-2 positive. This finding makes intuitive sense. Aspirin is a COX-1/2 inhibitor.
I googled “colangiocarcinoma COX-2”. I found a few studies that suggest that COX-2 is overexpressed/upregulated in CC.
Putting two and two together, it’s seems logical to come up with a theory that low-dose aspirin might be of benefit to some CC patients.
We talked to our surgeon and radiation oncologist about safety of low-dose aspirin after Whipple / chemoradiation. They both said that low-dose aspirin should be okay. The surgeon mentioned that if my wife is really unlucky, she might develop GI bleeding. But this is also true in healthy people.
It did cross my mind that maybe we should request an Rx for a COX-2 inhibitor such as Celebrex. Somehow that didn’t feel right (the evidence is rather flimsy). Naturally, I jumped in my seat when I read that you were taking Celebrex.
What do you think?
Best wishes,
Eli
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