tag:blogger.com,1999:blog-3165131923857031708.post8849043570977847084..comments2023-08-28T02:56:25.402-07:00Comments on Dr. Sharman's CLL & Lymphoma Blog: Take your pills - ibrutinib dosing matters!Unknownnoreply@blogger.comBlogger13125tag:blogger.com,1999:blog-3165131923857031708.post-56928079899096116292015-05-29T08:26:17.994-07:002015-05-29T08:26:17.994-07:00This dosing point raises the concern for patients ...This dosing point raises the concern for patients having to stop ibrutinib for minor surgery (3 days before and 3 days after) or longer periods for major surgery. This would seem to increase the chances for a relapse. Not holding the drug for surgery presumably may have its own problems but has this in fact been established or is the holding based on concerns for what might happen? Seems to leave the patient between a rock and a hard place. Anonymoushttps://www.blogger.com/profile/05339239268565592492noreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-70612169009781228582015-05-27T12:34:41.742-07:002015-05-27T12:34:41.742-07:00Dr Sharman, do you think the effects of dose reduc...Dr Sharman, do you think the effects of dose reduction as described in your blog would be the same for CML where the suggested dosage of Ibrutinib is 560mg (4 tablets)? Why does it need to be a higher dose to begin with!mocathttps://www.blogger.com/profile/08131067682810810746noreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-64917191258859308672015-05-26T12:31:04.718-07:002015-05-26T12:31:04.718-07:00I am doubtful that this is coming soon. Makes rea...I am doubtful that this is coming soon. Makes reasonable sense. We do similar things in HIV. Works best when the two drugs work at different locations of the same enzyme. The Acerta compound and the Gilead compound (from ONO). and the Celgene compound (CC-292) all bind at Cys481 so unlikely those would be combined. Maybe other BTK inhibitors out there targeting other locations (I'm aware of at least one). More likely, it will be combinations with other good targets such as Syk, PI3K, BCL2, CD20, PD-1 or others - but ONLY in context of clinical trials for now. Do not do this on your own.JAGhttps://www.blogger.com/profile/13844336136808999715noreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-9407462614984000082015-05-26T08:46:20.699-07:002015-05-26T08:46:20.699-07:00Do you think that someday there might be a rationa...Do you think that someday there might be a rationale to use 2 different BTK inhibitors at the same time, if they both work as single agents but have different binding sites (since BTK inhibition works and side effects appear to be manageable, but 1 BTK inhibitor doesn't inhibit 100% of BTK)? Thanks! Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-92199744471704297482015-05-20T08:44:59.074-07:002015-05-20T08:44:59.074-07:00Agree- interesting scientific question but current...Agree- interesting scientific question but currently no evidence to support doing this.JAGhttps://www.blogger.com/profile/13844336136808999715noreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-79754773941682646232015-05-20T08:44:33.552-07:002015-05-20T08:44:33.552-07:00CLL cells are continuously producing new BTK prote...CLL cells are continuously producing new BTK protein. Furthermore, not every single BTK protein is shut off in every single cell. Think of it more like a light dimmer instead of an on/off switch.JAGhttps://www.blogger.com/profile/13844336136808999715noreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-79456685423572899222015-05-20T08:41:46.149-07:002015-05-20T08:41:46.149-07:00Several "kinase inhibitors" in several d...Several "kinase inhibitors" in several different diseases are associated with a "rebound syndrome" after discontinuation. When I stop either ibrutinib or idelalisib, I try to keep pt on drug until next therapy ready to go or give a course of steroids.JAGhttps://www.blogger.com/profile/13844336136808999715noreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-85538451984185855812015-05-20T02:04:37.336-07:002015-05-20T02:04:37.336-07:00I'm currently on Ibrutinib 420 mg/day for abou...I'm currently on Ibrutinib 420 mg/day for about six months so far. In regards to my CLL it's worked brilliantly to shrink nodes/spleen to normal, and my counts never went far out of normal range either. Side effects I ascribe to Ibrutinib are broken capillaries in my skin at various spots, fragile finger nails, skin cracking at my fingertips, and (this one isn't bad) curly hair!<br /><br />"When you swallow a pill of Ibrutinib it gets into the bloodstream and either quickly binds to the BTK protein or it gets eliminated from the body. Within just a few hours of taking a pill there is virtually no free drug in the blood."<br /><br />Given the rapid clearing, why isn't it better to take 140 mg every 8 hours, rather than <br />all 420 mg at once each 24 hours?<br /><br />ThanksAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-51141904522084771222015-05-19T22:04:08.595-07:002015-05-19T22:04:08.595-07:00Im having a hard time understanding how resistance...Im having a hard time understanding how resistance could form since there is an irreversible bond being formed between the cells and the medication. In my mind every cell that is affected by ibrutinib is "turned off" and all other cells not reached by that dose are not affected. It seems like its all or none and there is no partial response allowing cells to adapt.<br /><br />An issue along the same vein comes to mind when my father was taken off of his regular dose of ibrutinib because he was given an antifungal (voriconazle) that was said to inhibit its metabolism. In my mind , if most the medication is binding to cells than I would think that its actual metabolism wouldnt be much of an issue since its now bonded to a cell and wouldnt go through its normal metabolic pathway. Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-73316595867294303482015-05-19T19:59:23.226-07:002015-05-19T19:59:23.226-07:00Great item. I have been on Ibrutinib for 15 month...Great item. I have been on Ibrutinib for 15 months now and my numbers are near normal. Chemo is not for me! I am 11q with skin cancer issues that concern my local oncologist. I'm trying to make him understand that my skin cancer issues go back to the 1980's. I grew up in the Miami, Florida area and spent all summer at the community pool. I also lived in Hawaii for six years sailing, swimming, golfing jogging, etc. My local oncologist is concerned that Ibrutinib is causing my skin cancer. Hopefully items such as yours will calm him down. Bob and Kathy's Travelshttps://www.blogger.com/profile/11251249252106929241noreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-68117930098429256692015-05-19T15:23:10.534-07:002015-05-19T15:23:10.534-07:00Dr. Sharman,
I am very appreciative of all the gr...Dr. Sharman,<br /><br />I am very appreciative of all the great work you are doing and taking the time to write your blog is amazing. I was recently diagnosed with CLL and your blog has really helped me to better grasp what I am (and will be) dealing with.<br /><br />Here is a possible link to the poster (if it helps): http://www.researchgate.net/publication/268039410_Population_pharmacokinetic_model_of_ibrutinib_a_Bruton_tyrosine_kinase_inhibitor_in_patients_with_B_cell_malignancies<br /><br />Thanks again!Ross Braggnoreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-46197649314775540032015-05-19T08:11:59.945-07:002015-05-19T08:11:59.945-07:00Thanks for this informative article and - in gener...Thanks for this informative article and - in general - for your blog! It's very readable and understandable to non-medical professionals and patients (I'm an MCL survivor... at least for now!). Namaste...Anonymoushttps://www.blogger.com/profile/07732266140922886985noreply@blogger.comtag:blogger.com,1999:blog-3165131923857031708.post-63185477016426358302015-05-18T22:04:33.622-07:002015-05-18T22:04:33.622-07:00Dr. Sharman,
Can you please speak to your underst...Dr. Sharman,<br /><br />Can you please speak to your understanding of aggressive progression for patients who discontinue ibrutinib, and how this may or may not be a function of dose adherence as discussed above?Anonymousnoreply@blogger.com