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Intermittent dosing of dabrafenib (tafinlar) and trametinib (mekinist)

Intermittent dosing of dabrafenib (tafinlar) and trametinib (mekinist)

Posted By
Anni
6/11/2019 1:19pm
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Replies: 6

Hello, I’m seeking information for my sister, diagnosed last August with metastatic melanoma, started targeted therapy on Tafinlar and Mekinist in September. Has since had good reductions in tumour six but had had bad side effects with aches, and severe shivers and shakes and temperatures. Intermittent dosing is not practiced in the UK, only currently done on trials, you can only go on trials before treatment stats, so this will not be an option for her. I’m wondering can anyone advise what regime they are following on intermittent dosing, ie.. is it 4 weeks on 2 weeks off??or similar. I would greatly appreciate any help, as she is suffering terribly with the side effects and her quality of life, we are also aware that intermittent dosing can prolong the effectiveness.
Thank you all in advance. Regards Anne Marie

Hi Anni, there might be other trials but this one is being run in England, here are two links that give details of trial set up. https://oncologypro.esmo.org/Meeting-Resources/ESMO-2018-Congress/A-rand... https://clinicaltrials.gov/ct2/show/NCT03352947

Thank you for this information Ed, I appreciate it, unfortunately they will only accept you on the trials prior to any commencement of the therapy. I was just seeking information on what doses and duration people on the combined therapy and following intermittent dosing were on. In the hope that she could maybe do it herself.

In the second link above to the trial, it explains the trial design that patients followed. My understanding of the trial design after reading the information in the link is that the arm of the trial that is looking at intermittent schedule stops at day 21 following a 28'day cycle for debrafenib and 14 day cycle out of 28 for trametinib. I have no experience with either of these drugs myself or the trial but this is how I see the design of NCT03352947.

Hello Anni, i am on this combo and because of side effects am on reduced dosage and in effect been on intermittent dosing as well because of taking breaks when erythum nodosum becomes to numurous and painful.It worked out that i ended up being on meds about 3 weeks and taking 2 week break till ED resolved.I have been on combos for 2 years now and one of my Dr.s said there is some history of patients that end up taking breaks from meds for symptom reasons have longer response to drugs before possible resistance sets in.That is what i have read from animal studies on the internet as well.There is a human study in the U.S. that is using a 1 week on combo 3 week off then 4 week back on schedule, so a 56 day cycle. ed has posted a link to it SWOG 1320 in a previous post on intermittant dosing about a week ago.
So i am now trying this routine started 3 weeks ago ,it comes down to 5 weeks on and 3 weeks off over the cycle.I have had good results from the targeted therapy even though lower dose and taking breaks as i am NED now.Wishing you and your sister luck.
Hope this is helpful,wish you

Hi, I’m sorry to hear of your sister’s diagnosis and side effects. My husband also has metastatic melanoma, also good results on the tumor and spots, also suffered the side effects you mentioned and was hospitalized for a few days because of them. He took a two week drug holiday at that time and when they restarted him they dose reduced the debrafinib by 25% and kept the trametinib the same as the original dose. He doesn’t have any of those effects anymore. He is on the intermittent trial with 5 weeks on and three weeks off. I would definitely recommend inquiring about a slight dose reduction first, maybe that will address the issues better than the intermittent drug schedule. Some people just don’t need the full dose, my husband has had good results with the lower dose. This is just our experience, I wish the best for your sister and you.

My husband has Metastatic Melanoma with high tumour burden. He is on TAF/Mek and had to take two breaks of 4 and 5 days due to severe side effects. He is now taking same dose but only Monday to Friday and has weekends off. Side effects have gone and tumours shrinking.