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TORADOL (ketorolac) linked to Recurrence Prevention

My mantra for medical and nursing information for decades has been " Just when you think you know something look again" I thought I was done searching for an answer yesterday on something else, then I listened, "You don't know enough, look again, you don't know enough look again". That pesky little irritating voice that drives me. I looked again and came upon the Retsky study. This is groundbreaking research as is the Forget study. A leap forward.

There has been ongoing research that is looking at the specific use of Torodal(ketorolac) in the perioperative(preincision) phase of breast surgery. The initial study was from Belgium. This study is known as the Forget study published in 2010. A particular isolated group of patients that had an unusually low rate of breast cancer recurrence. All had the same breast surgeon and one of two anesthesiologist. The anesthesiologists had a common approach to drugs used for surgery. Toradol was the common drug given intraoperative.

These studies are retrospective studies which makes it more difficult to consider the use of Toradol/ketorolac for your breast surgery. Review the studies, talk with your surgeon and anesthesiologist pre-op. Ask specifically if they're is any reason that Toradol is contraindicated for use with your surgery. There ARE patients that it should not be given too. This drug is routinely used in surgery, the question is not out of bounds. We (myself and Falleaves) have prepared two posts that contain the needed references that will link to the studies. Copy and give them to your docs.

4/1/2016 There are prospective studies underway

4/1/2016 this video is by Dr. Vikas Sukhatme. He is a co-author with Dr. Retsky. Dr.Sukhatme is academic dean at Beth Israel Deaconess Medical Center at Harvard.

https://www.youtube.com/watch?v=H8zVrYEW8vE&feature=youtu.be

This link is to an article about the Dr. Forget study, 2010. Patient cohort 327.

http://www.medscape.com/viewarticle/723293

Dr. Forget' s study. This is benchmark original research.

http://www.ncbi.nlm.nih.gov/pubmed/20435950

Dr. Forget' s study 2014. Follow up retrospective study of the 2010 retrospective study. Patient cohort 720.

http://bja.oxfordjournals.org/content/early/2014/01/23/bja.aet464.full.pdf

Dr. Retsky' s study is a broader based analysis of Dr. Forget' s

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831877/

Multimodal Hazard Rate for Relapse in Breast Cancer: Quality of Data and Calibration of Computer Simulation. 2014. Dr Retsky.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276970/

The "Best of Antiangiogenesis" is a series of webcasts, generated through Project ENABLE™, featuring presentations from leading medical experts describing research and perspectives on new angiogenesis-based therapies. 2012. Dr Retsky is one of three presenters.

https://www.angio.org/learn/multimedia/#webcasts4

Dr Retsky presentation from above, but only him .... YouTube https://www.youtube.com/watch?v=sk5ZKV-4tgo&feature=youtu.be

////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////


Links to BCO threads that are related to this topic:

Topic: Paravertebral Nerve Block and Propofol Sept. 2015, by Falleaves

https://community.breastcancer.org/forum/73/topic/834546?page=1#idx_15

Topic: Effects of opioids on cancer progression Sept. 2015, by Falleaves

https://community.breastcancer.org/forum/73/topic/835291?page=1#idx_

Topic: ketorolac to reduce recurrence Mar. 2014, by Falleaves

https://community.breastcancer.org/forum/91/topic/818961?page=1#post_3936891

Topic: Anesthesia and recurrence of cancer Sept. 2015, by Fallleaves

https://community.breastcancer.org/forum/73/topic/835244

Topic: NSAIDS and Breast Cancer Sept. 2015, by 123JustMe

https://community.breastcancer.org/forum/73/topic/835343

small study comparing the impacts of IV morphine, tramadol and ketorolac on the immune response

http://www.ncbi.nlm.nih.gov/pubmed/26710216


/////////////////////////////////////////////////////////////////////////////////////////////////////////////////// Topic: Discussion Topic: Record of Surgical Managemet, and Recurrence (incomplete)https://community.breastcancer.org/forum/73/topic/835528 Topic: Record of Surgical Managemet, and Recurrencehttps://community.breastcancer.org/forum/73/topic/835525?page=1#post_4516040//////////////////////////////////////////////////////////////////////////////////////////////////////////////////Dr. Gwen Stritter after Mastectomy https://www.youtube.com/watch?v=IkKEFF_c0yo/////////////////////////////////////////////////////////////////////////////////////////////////////////////////Topic: Ways to Reduce Recurrence Risk: Ketorolac, Blocks, Opiodshttps://community.breastcancer.org/forum/26/topics...


I will revise and add as I find things--sassy



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Comments

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    All drugs have consequenses, I've started the discussion with the Black box warning re: Toradol (ketrolac). Always important to understand everything you can about a drug when you are considering using it. Safe approach.

    ketorolac

    generic

    Drug Monograph

    Black Box Warnings .

    Appropriate Use

    for short term (<5 days in adults) tx of moderately severe acute pain requiring opioid-level analgesia and only as continuation of parenteral tx, if necessary; total combined duration should not exceed 5 days; not indicated for minor or chronic pain; oral tx not indicated in peds; max recommended total daily dose 40 mg PO and 120 mg IV/IM; doses above label recommendations incr. serious adverse event risk w/o improved efficacy

    GI Risk

    incr. serious GI adverse event risk, incl. bleeding, ulcer, and stomach or intestine perforation, which can be fatal; may occur at any time during use and w/o warning sx; elderly pts at greater risk for serious GI events; contraindicated in active PUD, recent GI bleeding or perforation, and PUD or GI bleeding hx

    Cardiovascular Risk

    may incr. risk of serious and potentially fatal cardiovascular thrombotic events, MI, and stroke; risk may incr. w/ duration of use; possible incr. risk if cardiovascular dz or cardiovascular dz risk factors; contraindicated for CABG peri-operative pain

    Renal Risk

    contraindicated if adv. renal impairment or if renal failure risk due to volume depletion

    Bleeding Risk

    contraindicated if suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or high bleeding risk because inhibits platelet fxn; contraindicated as prophylactic analgesic before major surgery

    Labor/Delivery Risk

    contraindicated in labor/delivery because may adversely effect fetal circulation and inhibit uterine contractions; contraindicated in nursing mothers due to potential adverse effects of prostaglandin-inhibiting drugs on neonates

    Concomitant NSAID Use

    contraindicated in combo w/ ASA or NSAIDs due to cumulative risk of serious NSAID-related side effects

    Intrathecal/Epidural Use

    contraindicated due to alcohol content

    Hypersensitivity Rxn

    hypersensitivity rxns range from bronchospasm to anaphylactic shock, have appropriate tx available; contraindicated if previous ketorolac, ASA, or other NSAID hypersensitivity rxn

    Special Populations

    max total daily dose 60 mg IV/IM if pts 65 yo and older, wt <50 kg, and moderately elevated Cr; max single dose 30 mg IM and 15 mg IV in peds pts


  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    While they're numerous drugs grouped as NSAIDS. They don't work the same way. The anti-inflammatory cascade is different depending on the drug.

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    BUT and it's a big BUT........ I will not have surgery again without the discussion. At present time I do know that I have no contraindication for the drug limited to one time use. Toradol is used IV up to 6 doses post-op /6hrs. Toradol is rare to be given my mouth in the hospital setting. Rare outside of the hospital as a prescription b/c of the GI problems. Great drug for short term use. It's an old drug that has stood the test of time, roughly two decades.

    What I'm going to do is get the anesthesia record from Medical records to see if Toradol was used. Hopefully it hasn't been expunged. Toradol was part in parcel of almost every surgery at the hospital I had my surgery.

    Anesthesia folks are as obsessive compulsive as many others are. In the Forget study, two docs. essentially used the same plan. The plan is pretty universal. People that administer drugs on the anesthesi level know that drug so well, the a small change in the patient under anathesia, they got it. Clonidine is a centrally acting vasoactive blocker drug. Ketamine--paralyser, sufentanil, think fentanyls burley strong dad, for pain control. Hmmm no Versed. None of the 4 have amnesic qualities. Is frequently given technically outside of the operating room doors i.e pre-op,so, it's considered a pre-op drug. If you remember the OR, they gave it in the room or to late in pre-op

    With this new(to me) information added to my understanding of anesthesia folks, I can make some observations. Anesthesia takes the history of the patient and determines the score. They're is a pretty cook book approach to basic anethesia. Each level has quidelines. Anesthesia won't take risks, unless the patients life is at risk. Anesthesia folks are excellent at keeping abreast of changes in the field and publications that have anything to do with their field. Guess, but a good guess based on knowledge of anesthesia doc and CRNA's, they know this potential of Toradol is out there. It's already being used with this in mind.

    I predict that in 2016 forward we will start to see a drop in 10-12 month recurrence and the pattern described by Retsky, will be observed. The a retrospective analysis will be done to look at numbers.

    What I don't agree with Retsky is that the first trial be done on triple Neg BC patients. Per his statement that this would be the fastest way to determine if the drug worked b/c of the statistical recurrence is short. Nope. Anyone in their right mind that would withhold a drug, that costs a few bucks, routinely used worldwide, one time to max usage 6 doses, that person would be criminal. I know the laws prevent that in trials. But anything less than Toradol right now the risks are to great for a negative outcome.

    EDIT: 9/28/2015. Allot more study and allot more understanding has occurred since writing this, my soapbox stand on a triple negative study is not well reasoned. The learning continues.

    Enough pontificating, going to play. sassy

  • Loveroflife
    Loveroflife Member Posts: 4,243

    Darn it lost a long post. Now I don't remember what I wrote. Don't remember what happens at cellular level during surgery, but I know for sure Prostaglandins are released. Toradol is the most potent NSAID with most serious side effects. 30 mg of Toradol has the same analgesic effect as 10 mg Morphine. We know that PGs promote tumor growth and NSAIDS help decrease PGs. From what I understand, anti-inflammatory effect is achieved with Toradol only at doses higher than those needed for analgesia. Toradol,if used, is given at 30 mg intra-op and more at the discretion of the surgeon (per SIL who is a nurse anesthesiologist). I would think you do get some decrease in circulating PGs at 30 mg. Hope this makes sense.

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    Loverly, the exciting answer is best presented in Retsky's study. The theory is there, if it pans out. It changes the paradigm

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    This is a portion of my response to a member from a PM.

    "Normally, I wouldn't introduce this to a Newbie in this vulnerable period of disbelief, but it can greatly impact you if you are having surgery. It's mainstream science. BUT it hasn't reached mainstream practice. The research was first published in 2010. Forget and Retsky have each published multiple times on the topic. If their observations are true. It's revolutionary. The science forum doesn't get that much traffic. Basically, I think it's b/c the material is to complicated to read.

    I think start with my topic box comments, then my posts, then the link to the article, then the studies. This if it pans out, can reduce recurrence. At this point it's on your agenda because surgery is in the future. Toradol is used routinely in breast surgery(as in many, many surgeries). But it is an  anesthiologist choice. If they're is no reason not to use it. Ask that it be used.

    Please, try to look at it. Sorry if I seem pushy, but it's important."

    Toradol is so routinely used in surgery, it's almost a "Ho-Hum, yeah," thing.

     It's a two for one drug i.e. two actions. 1. pain- it hits different pain receptors than the opiods. A previous post said that it had an equivalent pain control as Morphine 10mg. But I want no confusion here, Opiods hit opiod receptor sites. NSAIDs hit other non-opiod receptor sites. When you add that amount of pain control by the opiods and NSAIDS together---it's very nice(understatement). 2.NSAIDS interfere directly with the cascade(domino) effect of the inflammatory response.

    This inflammatory response is the crux of how Toradol may be connected to prevention of recurrence with BC. Further research has to be done to see how it influences other cancers. Research has already shown that it doesn't influence prostate cancer.

    Tissue when it's cut alerts the body that it's been hurt. An incision is a very tidy cut, but it is skin disruption.When the skin is disrupted, the body responds from the brain level with alerting different body parts to protect itself. Other cellular mechanisms start on their own. All these different cellular chemicals start acting. That's what we refer to as the cascade of the inflammatory response.  A>>b>>c>>d. Marvelous design. The major organs are controlled by the brain. The small patrol units that are circulating in the blood stream all the time quietly waiting for trouble. They start within seconds of an injury.

    Please, take the time to read the material, don't assume someone else can tell you. They may not be up to date on the reading.

  • 123JustMe
    123JustMe Member Posts: 169
    Interesting info! I looked at my discharge instructions from the hospital including all medications given during surgery and Toradol 30 mg. was given.
  • hopeful82014
    hopeful82014 Member Posts: 887

    Another member had posted info about Toradol last year (if I remember correctly) and was very kind and helpful in answering my questions about it.

    One surgeon told me there was no way she would allow the use of it but she would not have been a good choice for me anyway. The surgeon I eventually chose had no issues with using it and was happy to insure that I did receive it. I would not have known about Toradol if not for this site.

    ETA - Thank you, Sassy, for raising this issue again. I think it needs to be brought up periodically so that other women know to request it - and push for it, if need be.

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    Hi, 123J Thanks for posting. Interesting that they gave you a list of drugs inclusive of OR drugs. I'm impressed. You should have some fun with reading the studies b/c you are in the group that may have been protected from recurrence. Again it won't be solidly known for several years. Would love to have you look back years from now and say "I was in the early days"

  • 123JustMe
    123JustMe Member Posts: 169
    From your lips to God's ears, Sas!
  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    Hopeful, I'll do a sight search and bring that topic forward if I can. If you find it tell me . I'll link it to this topic by a link in the topic box. That gal was very on top of the info. I happened on the studies when I was helping a gal on the port thread that I monitor. It was a "No chit' moment. You know me Hopeful, once I get on a bandwagon, I ride it. LOL

    Immensely happy you 'gotter done'. So, cool for you. Was the Toradol issue the only reason you didn't go with the first surgeon? Did you take the study material? Was the surgeon familiar with it or was it she was honoring your request?

     My  pathology was so bad, right there in front of me was 'unfavorable outcome'. No clue why, I'm here. According to Retsky's hazard/chaos analysis I've passed the first two trouble times. I still have hopes of retrieving the OR/anesthesia record to see if it was used.

    YAY HOPEFUL--you done good.

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    Okay thanks Hopeful, Finding some links they are quoting the same Retsky and Forget studies. As an aside. Forget's name. I keep thinking what would Abbott and Costello do with the name i.e. 'who's on first'

    https://community.breastcancer.org/forum/91/topic/818961?page=1#post_3937147

    will bring them as I find them

  • hopeful82014
    hopeful82014 Member Posts: 887

    I'll find the thread for you later today, Sassy.

    No, the Toradol issue wasn't the only reason, by any means. It was more of an indicator of her overall attitude. She was truly toxic. I had supplied her with the published material and she basically said, 'well, that's just one small study. I'd need more evidence than that' and went on convince me (inadvertently) that she was not the surgeon for me.

    The surgeon I ended up with was happy to read the study, kept a copy for her files, said she had used it post-op but would be happy to do so pre/intra op and made sure it happened. Her attitude was as different, and refreshing, as could be.

    I also ended up with an RX for it for post-surgical pain relief, as I do NOT do well with opiates. That worked out well - use was limited to 5 days (which was fine) and I had to be sure to consume some food with it.

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    Hopeful textbook use of Toradol. God bless her. Please, do me and all of us a favor. Contact her and see if it influenced her practice? The reason I predicted that we would start to see a change in recurrence in late 2016 and beyond is b/c of this research by Forget and Retsky. If you look at the recurrence trends by Retsky, they follow a predictable pattern. If Retsky and Forget continue to publish metanyalsis data, and the same trends are seen. Each publication increases the compelling connection. Plus, they are publishing in different journals and internet. They are trying to saturate the medical world with this. Not unusual when researchers take on a soapbox item. They are out to change the world

    The scientific method by today's standard requires a double blind study. This standard was formalized in the late 40's. If the meta- analysis is so compelling how do you divide the group. It's like the BC vaccine trials. Lives are stake.

  • Smaarty
    Smaarty Member Posts: 2,618

    ok sassy, I know I had toradol given when I had the bladder sling put in, with the hysterectomy and the gall bladder. I know because it made the pain in my foot go,away for about 2 weeks after each surgery. So I asked and got a prescription of it. I know you're only suppose to take it a max of 5 days. Never took more than 1 piil a day for,a,couple weeks. Mostly no more plantar f now.

    All before BC. I'll have to pull my records,and see if it was given for any of the BC sx.

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    Thanks Smarrty, I find your post interesting b/c you have three time use of the drug, that you were able to associate with another inflamed area. Then a short term use of the drug corrected that problem. HMMMMmmmmm.....gawd wish all dugs worked that way.

    Hopeful I found only the one link above. Many posts about Toradol associated with procedure. Check four posts back and see if that was the person you talked with

  • 123JustMe
    123JustMe Member Posts: 169
    I am not sure why there isn't a large randomized study on this!?
  • 123JustMe
    123JustMe Member Posts: 169
    I wonder why there isn't a large randomized trial on the use of NSAIDS and breast cancer?!
  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    123J, Retsky suggested at the end of his study that the quickest way to determine if the connection between recurrence and Toradol was to do a trial using Triple Negative BC patient's b/c  they have the fastest time to recurrence. I love his research, but that took my breath away. In print it was so cold. Can't imagine being in that trial.

    The two of them are building such a compelling case for Toradol. No idea how this is dealt with? I'm a post polio kid of 1952. Trials went on from 1936 till my time. Salk vaccinated his kids in June 1952. I and 3 siblings had polio in September that year. I only know this b/c it was in his obit. I looked at the obit. Tears. Polio negatively affected my entire families life. To be so close yet so far away. FDA didn't approve it until 1954.

    The studies will be done, but we have some control. Just like Hopeful did with her doc. Present it. If you believe the studies are valid. Don't settle for less than receiving the drug.

    The drug is 20 years old. Routinely used in many surgeries world wide. They're specified black box warning situations that it shouldn't be used in. If you don't fit the scenario for a black box warning issue. How can the drug be withheld?

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    123j the danger here is folks reading this will take NSAIDS over the counter(OTC). May not use them right. May not pay attention to Black Box warnings. May not pay attention to drug interactions. Then the worst case scenario do the 'more is better' approach which could lead to very bad stuff i.e GI bleeding.

  • 123JustMe
    123JustMe Member Posts: 169
    Sas, Do you know of any post surgical trials where long term NSAID vs placebo are prescribed? It seems like such a reasonable study to under take.
  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    123j nope, but we can follow up on that this week. Sunday night time to go bother DBF.

  • MarlanaB
    MarlanaB Member Posts: 193

    Sas -- I had Toradol in hospital after my 2nd knee surgery in 1994 (a tibial transfer or patellar realignment). I was only supposed to be in overnight but they wouldn't release me until I could stand up on my crutches and walk down the hall...I don't do well with any pain meds since they make me seriously loopy and I'm allergic to morphine. At first, I was given demerol and couldn't even stand up without falling over. After 48 hours of that, I was switched to vicodin and I was seeing double. I was finally switched to Toradol on the 4th day and finally able to walk down the hall on the morning of the 5th.

  • 123JustMe
    123JustMe Member Posts: 169
    I wonder how often C-RP levels are checked prior to treatment for BC patients?
  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    123, google keyword crp and cancer, then crp and breast cancer, then crp and heart.

    On the trials, preapproval. Ibuprofen was the first  bbl still want to play

  • 123JustMe
    123JustMe Member Posts: 169
    Sas, I think I've googled enough to make me scared and dangerous LOL! I have an appt with MO on Thursday and if there are no surprises in the path report I plan on asking about getting my C-RP and Vitamin D level checked. Sounds like people with high C-RP levels have worse outcomes :(
  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    Has to do with the whole inflammatory response thing. Bad for all body parts and function. I wrote some stuff on Vita d, I'll get the link. It's an inactive thread that I store drug info on.

    https://community.breastcancer.org/forum/102/topic/826526?page=4#idx_102

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    One active study in Assiut Egypt. No other info than it is a comparison of three drugs in mastectomy patients. Comparison between the effects of intravenous morphine, tramadol and ketorolac on stress and immune responses in patients undergoing modified radical mastectomy

     

    Effect of Morphine, Tramadol, and Ketorolac on Postoperative Stress and Immune Responses

    https://www.clinicaltrials.gov/ct2/show/NCT02449954?term=Toradol+and+mastectomy&rank=1

    keywords Toradol and mastectomy.

    They're 261 studies listed at clinicaltrial.gov. Only the above one was related to BC

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    http://www.nlm.nih.gov/medlineplus/druginfo/meds/a693001.html

    Toradol info. If considering asking your doc to use in surgery. Review this monograph.

  • sas-schatzi
    sas-schatzi Member Posts: 15,875

    123  455 trials on Ibuprofen, sort through LOL, my mind got lost. I'll try it again if I find it :)

    https://www.clinicaltrials.gov/ct/search?submit=Search&term=IBUPROFEN