Hi All, hope all is well. Need a little encouragement. About A week out from my six month post diagnosis. Fortunately no side effects so far except labs. I had an appointment about a month ago and my liver enzymes were around 300. We monitored it and it went down to 184 about a week later but it went back up to the mid 200s.Also my platelets were at 44. My doctor has stopped me from taking 100 mg Sprycel. He’s going to do bloodwork on Friday and hopefully my labs come back somewhat normal. He intends to start me back up on 70 mg. Is this very common to go off meds because of bloodwork? Do I need to worry about resistance or mutation? I’ve had no physical side effects associated with the meds. Any advice or guidance would be helpful.
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Dose adjustments and even being off TKI for a short time is quite common after diagnosis. I am glad you do not notice any side effects, it is good. However the lab side effects are more important on medical side, because you cannot die of bleeding, infection or liver failure... This does not mean you are resistant, it just means that the meds affect thrombopoesis a little bit more than acceptable. In my case I started imatinib 400 mg and finally settled on 250 mg ( I am lightweight small girl 😁) with good results according to standard treatment milestones. I had some unappreciated side effects, but the main reason for reductions was my low platelet count. Do not worry, even less than 70 mg Sprycel could work. It is always better just reduce the dosage than stop medication completely, but this is good idea and usual in such low platelets. It needs to recover a little.
What your doctor should consider doing (which my doctor did and he is a top researcher in the field) was restart me on 20 mg sprycel. He told me when he sees suppression like you are experiencing as well as liver enzymes going up, he re-starts at lowest dose and works up as needed.
You may find that at 20 mg, you respond very well and begin to tolerate the drug just as well. You may not even need to have your dose increased at all and stay at 20 mg.
This is what happened to me. I had blood suppression on 70 mg sprycel and my doctor took me off - let my counts recover (took many weeks) and then re-started me on 20 mg sprycel. What happened next was dramatic. Within weeks, my PCR plummeted and I quickly became MMR. Now, I am "undetected" (3 years) all while taking 20 mg. sprycel (which I now take every other day preparing to stop altogether).
Lowest dose is best if lowest dose works.
If your doctor expresses concern about "resistance" explain to your doctor that cancer is not the same as bacteria. More drug does not necessarily lead to more response in the case of sprycel and can, in fact, lead to poorer response if dose is too high for that individual. Dose discovery is vital.
Hi All, quick update... did blood work today and liver enzymes are still elevated but decreasing (ALT 149/AST 91). Last Tues was (268/131). Onc wants to hold 50MG Sprycel another week to get them back to normal. Still emphasizes that resistance shouldn't be a major concern. I mentioned that if 50mg gives me the same problem would we drop to 20mg and he said we'd move on to another TKI. Does that sound right in regards to med hold and switching TKIs?
I'm new to the Forum & have been very interested in your posts re. dose reduction of TKIs & use of complementary medicines such as curcumin, vit D3 & K2, magnesium etc...
My mum who's now 80 was diagnosed with CML in Aug 2018. Was on imatinib (initially 400 mg per day but then dropped to 300 mg due to platelets dropping dangerously low - I actually insisted on the dose being reduced after doing some research). She was then put onto dasatinib (100 mg daily ) which caused drug related pleural hypertension and after 33 days was advised by her oncologist to stop dasatinib. I actually noticed her breathlessness & insisted on her having an echocardiogram which diagnosed the pleural hypertension. Her bcr-abl dropped dramatically whilst on dasatinib from 20 to 12 in 2 wks. I asked if she could stay on dasatinib but on a lower dose but was refused and told to swap to Nilotinib/Tasigna. After discontinuation of dasatinib for over 1 month & no TKI therapy, her bcr-abl rose to 74. Once on Nilotinib 2 x 200mg her bcr-abl went down to 24 within 2 wks only. But her oncologist increased the dose to 3 x 200 mg & then eventually on the max dose of 4 x 200 mg daily.
When she was on 4 x 200 mg her liver enzymes including bilirubin levels had dramatically increased & she had an inflamed gall bladder in addition to feeling chronically fatigued. She was advised to have her gall bladder removed via surgery. In my research I noted that one of the side effects of Nilotinib is increased liver enzymes and bilirubin and inflamed gall bladder. But the oncologist refused to link the two. My mum's organs were always normal previously. I insisted that the dose be dropped back to 3 and then to 2 and during this time, her liver and bilirubin levels have gone back to normal & she doesn't feel as fatigued. Her bcr-abl is now 0.54 & her bloods including white blood cells are more or less normal. She's been put back to 3 tables for the past month as her bcr-abl only moved down from 0.56 to 0.54 in the past month so hopefully now that her liver has recovered it may adjust to the increased dose & further reduce her bcr-abl.
I do believe in dose modification where serious side effects exist as these TKIs aren't as "targeted" as they make out. And I'd rather my mum have quality of life then having a zero bcr-abl and die as a result of the toxicity shortly thereafter - which as occurred. But I do feel that I'm doing this on my own & it's very much a guessing game when I consult with the oncologist who often can't or won't give me any solid advice. I'm left to doing my own research.
Having read your posts re. use of curcumin, magnesium, vit D3 & K2 etc... and consulted a naturopath my mother is now on these supplements which are taken at least 2 hours + before taking her Nilotinib so as to limit any interference. I've also given her some B complex & iron to help with her fatigue & always check with blood test for current levels.
Her liver seems to have come down in size after the dose reduction but her spleen has remained enlarged. She has a Jak2 V6178 mutation also which again my oncologist doesn't seem to be able to give me any solid advice on. After I did some research I found out that it's common for some CML patients to also have a Jak2 Mutation and a drug called ruxolitinib can be use to treat this and the enlarged spleen, in addition to using a TKI but it also has some serious side effects. My mum's GP advised me not to use it unless she has serious symptoms arising from the enlarged spleen as people can live with enlarged spleens as long as they don't have serious symptoms like dangerously decreased platelets which apparently is one of the side effects.
Have you heard of the Jak 2 mutation and any advice on how to best treat enlarged spleens - naturally?
Jak2 mutation is often associated with myeloproliferative neoplasms (MPN) and recently documented to potentially evolve into CML (2017) as well. You may have seen the link below:
Jak2 inhibitors of which ruxolitinib is one is prescribed along with a TKI to treat the condition. But given that your mom is very sensitive to TKI's (pleural effusion/ liver enzymes/ spleen) there seems to be much more going on in her bone marrow and spleen that should be investigated. I assume she has had a bone marrow biopsy to look at the hematopoietic niche for other chromosome abnormalities?
It is interesting to note Curcumin is a natural Jak2 inhibitor (more of a Jak2 pathway down regulator) and is very well tolerated by the liver. She could easily add Curcumin to her protocol and give an assist to her TKI treatment - but it takes a lot of Curcumin to get any benefit (8 grams per day) when considering cancer owing to its poor bioavailability and quick metabolism. I took 8 grams for at least a year until my CML was largely gone.
And finally there is strong evidence that 'starving' MPN's of glucose (fasting) alters the biochemical niche favoring MPN's
It is a complex area of research. If there were some way she could stay on a low dose of sprycel (20 mg) while avoiding pleural effusion, I would prefer that path for myself if I were in her shoes. Sprycel has shown to be excellent at low dose for patients who suffered pleural effusions while at higher dose. Lowering the dose to 20 mg led many to deep remissions. Sprycel also interferes wtih CML (and other neoplasms) pathways higher up in the cell hierarchy. A low dose sprycel coupled with a Jak2 inhibitor or just Curcumin (in case liver enzymes are an issue with ruxolitinib) may be an avenue worth pursuing.
Thanks very much for your prompt response.
My mum had a cytogenetic (bone marrow) test & flow cytometry done when 1st diagnosed in Aug 2018 & another one done in June 2019 when taken off Imatinib & before consideration given to going onto Dasatinib. Both cytogenetic tests showed the presence of the Philadelphia chromosome - consistent with CML. She later had a mutation test done which detected 47.2% Jak2V61F mutation. But the Jak 2 was never treated until I started to ask more questions after being taken off Imatinib & possible use of ruxolitinib. Having said this, when she was on Imatinib her spleen had eventually gone down but since being on Nilotinib it has increased to 23/24 centimeters notwithstanding that her bcr-abl levels have gone down & bloods are good.
Interesting about starving the body of glucose (and sugar). I've read about this in other articles and the naturopath did say to limit sugar where possible as it's alleged it feeds cancer. My mum is also a diabetic (diabetes 2) and during her Nilotinib treatment her blood glucose levels increased (side effect of Nilotinib) so I had her Janumet (diabetes 2 meds) dose increased from 50/500 x 2 daily to 50/850 x 2 daily. The 850 is metformin & the 50 is sitagliptin. The max dose of sitagliptim is 100mg and metformin is 2000 mg per day. I've also read an article about positive results in use of metformin in treating Jak 2 mutation particularly when used in combination with ruxolitinib which also decreases splenomegaly (enlarged spleen) : https://pubmed.ncbi.nlm.nih.gov/29472557/ Metformin Exerts Multitarget Antileukemia Activity in JAK2 V617F-positive Myeloproliferative Neoplasms I'm seeing my mum's GP next week so I may get him to prescribe the max dose of Janumet which includes 2000 mg of metformin whilst still on Nilotinib. Do you think this is a good idea or should I just get her to never use sugar (which I don't think she will as she likes her sugar).
She had her bcr-abl blood test done today (one month back on 3 x 200 mg Nilotinib) & will see where everything is at. Will get results next wk. Will also give serious consideration to your suggestion of going on the lowest dose of Dasatinib & ruxolitinib. Can I please ask why you think Dasatinib (at a lower dose) is better than Nilotinib when combined with ruxolitinib? I've read articles which also say that ruxolitinib & nilotinib can be used to treat Jak 2 & CML : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148771/JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo.
Hi all, update for me. Just got word (15May) that I'm undetectable! Very grateful, but also hesitant due to being off Sprycel temporarily due to elevated liver enzymes. I went off meds 11May and did my PCR 4 days after med pause. Hopefully that is good news. I will do labs at the 2 week mark and the plan is to start up 50mg Sprycel. I just had my 6 mo call with Dr. Mauro and he’s not to concerned about it considering how quick I became undetectable.
I forgot to ask you in my last response re. curcumin supplements. Are there any particular brands to buy as there's alot of supplements out there and since COVIC-19 there seems to be a shortage of imported brands into Australia. I did use Dr's Best High Absorption brand 1000 mg with black pepper extract (piper nigrum) for better absorption but haven't be able to get hold of it from the health food store and have purchased another brand called BIOGlan 1200 mg which also has black pepper extract? My mum's been taking two tables per day in addition to iron, b complex, biotin (for hair loss), vit d3 + k2, calcium and a magnesium supplement.
And given her Jak2 mutation and the research you sent me about the positive effects of curcumin do you think I should increase my mum's curcumin levels and if so to what level?. I know you said you took 8000 mg per day. Would 4000 or 6000 mg be ok?
Unfortunately she gets up set having to take so many tables, so If I were to increase her curcumin levels, which one of the supplements which she's currently taking would you suggest I drop?
This is the type of Curcumin I take:
Sabinsa licenses their formula to several manufacturers. Do an online search for "curcumin c3 complex" and you might find a supplier in Australia. Read the label closely to verify it is Sabinsa formulation. I buy mine through Amazon.
Eight grams per day is what clinical trials have shown to be effective. From what I read, Curcumin benefits are dose dependent At 8 grams per day, however, this Curcumin brand can get expensive. As mentioned I only did this for a year until my CML was in complete remission. I find 2 grams per day is perfect for joint pain (cox-2 inhibitor) and that is what I take currently.
"Curcumin is an inhibitor of NFĸB and has been shown to decrease NFĸB activation in human participants (Williams, 2017). To decrease NFĸB, participants consumed 8 grams of curcumin by mouth daily for 8 weeks and showed tolerance with no associated toxicities in patients with pancreatic cancer and other pre-malignant conditions."
Wild West when it comes to this stuff ... the ads on Amazon and such are enough to confuse anyone.
I just searched Amazon UK for “Sabina curcumin” and this comes up as top result:
Not one mention or Sabinsa. Obviously a key-word for search advertising, I suppose.