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Coming off Glivec

Apologies if this has been discussed before [well I know it has actually].

Anyhow, I was at Manchester yesterday and was discussing the side effects of Glivec with my consultant [I'm on 400mg]. He told me, that if my PCR stayed as it was next time I went to see him in 6 months time, he might reduce my dose, to combat the side effects. Now my PCR is negative, but it isn't undetectable.
The point of this post, is that he said that there were new reports that some patients had been taken off Glivec for two years and the CML hadn't returned.
Anyone heard that?

Hello Dennis
I had a short (2 week) break from Glivec 2 1/2 years ago. At that point I had been on Glivec three and a half years. This was because I was experiencing bad side effects. At that point my PCR was 0.000 After that short break my PCR has never maintained 0.000 and has slowly risen to the point where I was in danger of losing my response. This is something that others have experienced.

The side effects continued to be horrid, and I have just started on the Enact trial for AMN107.

I would urge you to discuss other possibilities with your specialist. Coming off/or lowering dose could cause problems.
ATB Pennie

Here's a link to an article in Blood about a small trial conducted in France that might be what your consultant was talking about:

http://bloodjournal.hematologylibrary.org/cgi/content/full/109/1/58

Nancy B from California

Hi Dennis,

The lowest I would reduce Gleevec to would be a dose of 350mg. A report from Dr. Mauro ay OHSU has shown that this is the lowest effective dose of Gleevec.

You could go lower than this only after you have had serum level testing that shows you can safely take a lower dose.

The only way that I would stop Gleevec would be in a clinical trial where I was monitored very closely.

Zavie

Zavie Miller (age 69)
Ottawa, Canada, dxd AUG/99
INF OCT/99 to FEB/00, CHF
Gleevec since MAR/27/01 (400 mg)
CCR SEP/01. #102 in Zero Club
2.8 log reduction Sep/05
3.0 log reduction Jan/06
> 4 log reduction Nov/06
zmiller@sympatico.ca

Hi Dennis

When I was on both glivec and dasatinib I had numerous breaks. If the break was short, say 2 weeks then my PCR was unaffected. When I had a longer break then my PCR did rise, ( I was never on the drugs long enough to be PCRU - but my PCR was very very low). I did find that my PCR dropped again when I went back on the medications.

The side effects did definitely diminish/totally disappear with the breaks but breaks are not necessarily the right answer and should only be taken under close consultant supervision.

I am sorry that you have such awful side effects and maybe another drug would be better for you. What side effects do you have?

Regards
Susan
www.caringbridge.org/visit/susanleigh

Susan

Dennis - this dose reduction idea is a bit of a conundrum for us all to understand, particularly given the minimum stated clinically effective dose.

We saw David Morin at the Hammersmith just before Christmas and he talked to us about Glivec dose. He said that they now knew that the different level of Glivec in the blood in different people has a very huge variation. The level in the blood can be tested but it is extremely expensive to do and is not at a level of cost where it could be used routinely in hospitals.

Val has had bad side effects on Glivec. particularly for 8 months of last year after coming off Glivec temporarily for three weeks before a stem cell harvest. David Morin has decided to put her down from 400mg to 300mg - she has had three "undetectable" PCRs in a row. That will happen once the present 400mg tablets are all used up. There will be no more additional monitoring over and above the usual three months. He seemed very confident that this was worth trying in an effort to reduce the side effects and he was as confident as he could be that it would not affect the PCR results. However, if it does, Val will go back up to 400mg.

I hope that adds a bit to the information posted here. I will let you know the outcome in a few months time.

Regards

David

hi Dennis,
as you can see from the replies to your post, this is a contentious issue and how patients experience side effects, as far as i can see, is the main reason for doctors to consider a reduction in dose.
Nancy has provided a link to a study in France ... if you follow that link you will see that the patients that did not replapse after discontinuation with Glivec were those that had previously been treated with Interferon.... here is a snip from the article:

"The BCR-ABL tyrosine kinase inhibitor imatinib mesylate (Gleevec) induces complete cytogenetic responses (CCRs) in more than 85% of patients with chronic myelogenous leukemia (CML). However, patients in CCR relapse after imatinib interruption in the case of detectable residual disease.1 In fact, fewer than 10% of patients achieve a molecular remission, defined by an undetectable residual disease using real-time quantitative–polymerase chain reaction (RTQ-PCR).2 We previously reported the outcome of patients with CML in CCR after cessation of interferon-alpha during the pre-imatinib era. Seven (all with a negative PCR) of 15 patients did not relapse.3 Here, we discontinued imatinib in patients with CML with undetectable residual disease for longer than 2 years, under strict monitoring of the reappearance of BCR-ABL transcript, using monthly RTQ-PCR. Relapses (ie, positivity of RTQ-PCR) were observed early after imatinib discontinuation in 6 patients. Six patients previously exposed to interferon for more than 6 months are still in molecular remission with a median follow-up of 18 months (range, 9-24 months) after imatinib discontinuation."

i am aware of other studies where patients with very low residual disease have stopped Glivec and replaced it with low dose Interferon.
i know of one person who is on this study and who has had successfully maintained low pcr's, without intolerable side effects, over the last 18 months or so.

for myself, i would not consider a reduction in dose unless i had a plasma level test beforehand. but then i did not suffer from severe side effects when i was treated with Glivec (600mg) apart from peri-orbital oedaema, so it is easier for me to say that.

the issue surrounding the 'sub-optimal' (below 400mg) dose is that this may lead to resistance and once resistance is established you would be in more difficult territory and other therapies would have to be considered, but i am sure you are aware of these consequences.

If your side effects are intolerable then maybe you should discuss the possibilities of changing therapy to Dasatinib, or getting on to one of the ENACT trials as Pennie has done.

side effects can be difficult for some to cope with and they do differ in severity, which is why i believe there is a need for a plasma level test in some cases.

best wishes,
Sandy

To everyone who has responded, thanks - you have ALL made some very interesting and useful points.
I had better start by explaining as briefly as possible, my position. I was diagnosed 14 years ago, with a white count of 400. Within 8 months of diagnosis, I had undergone an autologous stem cell transplant. That involved three weeks in isolation while my stem cells were harvested, followed later by another 4 weeks in isolation, having the transplant. Those procedures took a lot out of me. The transplant didn't work and within months the PH+ was 100%.
From there I went onto interferon. Somehow I stayed on interferon for another 8 years. During all that time, although the PH+ never dropped below 60% and went as high as 100% at times, my counts stayed absolutely stable. I put that down to the transplant somehow stabilising the disease.Then Glivec came to the fore. I got onto the trials and it saved my life.
Why tell you all this? Well the side effects have been pretty bad since the transplant. Extreme tiredness and very bad cramps being two of them.
Since Glivec, you can add very bad edema [as commented on by my consultant last week], Diarrhoea and even worse cramps. 14 years of treatment in my case has had quite some effect. So, the side effects are not ALL to do with the Glivec and reducing the dose will certainly not solve all the problems, but it would solve some of them.
The study that Nancy has posted, is probably what my consultant was referring to. Thanks Nancy. It is very interesting, but if I'm reading it correctly, those people being studied were all PCR negative? I'm not. On the other hand, the pople who didn't relapse were all originally on interferon. I was, for 8 years. [terrible treatment!] My consultant at Manchester is a top, top man. He is usually at the forefront of cml treatments. I was the first person to be harvested by the use of Hydroxyurea, rather than the Chemo previously used for this procedure. So he isn't sfraid to move forward with his treatments.
He also reassured me that no risks would be taken that allowed the CML to return. I must believe him when he says that. However, on the other hand, Pennie's post also gives reason for careful consideration. So, what to do - reduce the dose and go for less side effects under careful monitoring, Stay as I am where everything is stable, or look at changing drugs? I'm not convinced that the other drugs will alter my side effects, because as I say some of them are from the transplant/interferon era and 14 years continual treatment. Plus, Don't the other drugs have side effects of their own?

Oh and David - I'll be very interested to know how you and Val go on. Thanks.