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High Dose Glivec

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Hi All,

I wonder if anyone else has had experience of being treated with high dose Glivec either 600mg daily or 800mg daily?

I was dx in February 2007 nearly ten years ago and probably had a high WBC score and platelet count and in addition tests for blood viscosity indicated an abnormal score;at the time I was in Thailand and in order to be able fly back to UK had to self inject with blood thinning agent heparin for some days and also just before the 12 hour flight otherwise the oncologist in Bangkok said you might not survive.Yes a total nightmare but I guess all of us on diagnosis experience life changing experiences.

I had private health insurance and the day after returning started on Glivec 400mg and all went well with bcr/abl scores reducing as per plan and eventually with an MMR and a log 3 reduction.At that time of diagnosis insurers were starting to treat cancers and some funded tkis and targeted biological therapies such as Glivec but in my case only for a year-so it was back to the NHS with the same specialist.All went well until mid 2014 when I was put on a six monthly bcr/abl testing regime rather than 3 monthly  and then we had an aged/spoilt  sample so there was a gap of about 10 months when we had no bcr/abl scores available.Then in mid 2015 there was spike in scores to 0.393 which effectively meant that we had lost our molecular remission .We considered going on to nilotinib but never did;it is a long story and would not be professional to expand on reasons why treatment was not offered at that time.

Because we had still kept up the  insurance premiums, in late 2015 I asked the insurers if they would fund another drug such as nilotinib ;the response was that there had been an update of policy and they would now fund any tki including any licensed experimental drug- so were treated privately again..In August 2016 we found a new specialist and  had mutations analysis (there were none)and then monthly bcr/abl tests.If there had been new mutations it would have meant moving on to dasatinib or ponatinib.So the advice from Hammersmith to my specialist was try high dose Glivec first then if that does not work try nilotinib.Three months on 600mg Glivec reduced the pcr/abl score down from a previous 0.255  down to a much reduced bcr/abl score of 0.033-so now we have regained our molecular remission and am in safe territory well below that magic threshold of 0.1.

The essence of my story is that it is not difficult to survive CML as long as it is controlled down below 0.1 level or log 3 after having achieved MMR  but a score of 0.2 or  0.3 is too high and one is in a risky zone.

 Some believe that 400mg of Glivec was somewhat underpowered compared with later tkis;600 mg is quite a dose and affects the body in different ways such as giving an elevated CK score and muscular inflammation termed myositis .The problem was that without a higher dose of Glivec or another tki there was substantial risk of progressing and transforming to accelerated or blast phase-bleeding gums and a swollen spleen would be the first signs of transformation..

So we will continue to use Glivec at 600mg for the foreseeable future in order to try to attain a deeper molecular remission say down log 4 or more.Our specialist has never administered 800mg Glivec and we would not want to go down that path.

Basically we have experienced secondary or acquired resistance to the first line tki for reasons other than new mutations but it has been addressed with a higher dose.

Has anyone else experienced secondary resistance to a tki and has anyone had experience of high dose Glivec? I am not sure if NICE permits the use of high dose Glivec under the NHS because of the additional cost-600mg is about £3000 per month without VAT I believe .N .B. Primary resistance to a tki would occur in the early stages of treatment whereas secondary or acquired occurs after a number of years of previous successful response and treatment

With best wishes

John

I was on 600mg for 3 weeks, I had some problems with nausea (more than anything on 400mg)  but that may have been due to the generic I was taking (Veenat) rather than the dose....i'm not sure. 

 

Also based on one of the videos on this website, deep mocular response does not have an impact on survival rates  (or lack of deep response), it only has an impact on your ability to eventually come off tkis. But i guess you are concerned with remission? Are you saying as the counts edge back up to 1% then it will affect survival? 

ps: I also had 10 hours flying after diagnosis (with 2.5 million platelets) but no one thought to give me heparin....I wish they had, might have made my flight a little less nervewrecking :(

Ted was on 800 mg of Imatinib for at least 2 years. He responded very slowly to 400mg for the first few years, never getting into single figures,  but 800 mg sorted him out and brought his PCR down to around 0.2. He didn't really have any more significant side effects on the higher dose, and it never made any difference when he reduced back down, if this helps?

He's now down to 0.002 and he's coming up to 17 years with CML still on 400mg.  Stable and still rockin' and enjoying life!

600mg Glivec leads to rapid regain of MMR and deep remission-update

Hi All,

Thanks to Eva and Bee for your responses and for the information on the impacts of higher dose Glivec.Just to update a few years ago my bcr/abl score was moving towards 0.4% with a loss of MMR but  my latest score shows the percentage is down to 0.007% which is a sustained major molecular response and represents a 4.5 log drop from the state of play at diagnosis.

On diagnosis  in 2007 my scores were white cell count 61.4 with 4% blasts and  a platelet count of 976-current scores are WBC 4.55 and platelets 260 and all other counts very normal.  Because my white count was so high I made an attempt to compute my SOKAL score using inputs of age,white counts and blasts and in retrospect without the use of a TKI my lifespan would not have exceeded two years from the time of diagnosis-very salutary still  to reflect on what medical research and drug development has given us CML patients.

I am aware that there is some debate over whether we can truly gain CMR as there will be always be residual and not easily measurable disease present but it would be reassuring to try to move towards a log 5 reduction.

600mg Glivec is has become quite tough to tolerate and to take -however looking at previous posts on this forum  on the issue of severe nausea, occasional vomiting and severe headaches I now only take the dose with a high carb meal and lots of water ;beans on toast or a pasta dish seem to be the most effective in being able in the long term  to tolerate the drug.Inflammation of the leg muscles (myositis) still persists as do those dreadful night cramps

With best wishes

John

Curious about 61.4 WBC on diagnosis, is this the same as 614,000 /ml I wonder?  What are the normal range of WBC using your measure (61.4)?

I ask because I try to figure out how badly off I was when diagnosed, WBC was high but no blasts. I measured 335,000 WBC and the normal range would be 5,000 to 7,000. My platlets peaked at 2.5 million with a normal adult upper range of 300,000. I have read that WBC of 500,000 would be about 2 months from mortality untreated, but not sure if thats for acute leukemias only.

Wouldnt it be great if medical measure were standardised??