What is the case FOR drug therapy??

[GaryV]

Hi,

I don't want to come across negative, but I have some serious decisions to make.

My bone marrow has had 0% cellularity for over 4 years. My spleen is large against my pelvis. For months my HGB (7.3) and PLT (11) consistently have been critically low. Very occassional bleeding, except for everyday spotting. The only drug therapy I have been on has been Aranesp, which stopped working. I am transfusion dependent. RBC every 6-12 days; PLT becoming more frequent. They don't give much boost and the boost doesn't last long. I am not eligible for BMT.

As is, prognosis seems to be about a year (please no pep talks that no one really knows; I know, but it is a reasonable ballpark figure; I am not marking the calendar!)

My excellent hematologist recommends Dacogen if I were to go on drug therapy. My question is why would I want to do drug therapy?

1) Hypomethylating agents like Dacogen have side effects of anemia and lowering platelets. I am already critically low on both counts. I am already transfusion dependent and drug therapy will increase transfusion dependence, at least initially, with a hope that I will be free of transfusions for awhile in the future.

2) These drug therapies do not increase length of life (some evidence, not certain, they may increase life for 2 months or so).

3) Drug treatment side effects will reduce my quality of life for the time I do have remaining.

4) It will take 4 - 8 cycles (months) to know whether I get a boost.

5) Only about 50% of patients do get a boost and then for only a few months.

If my information is correct, I ask, what am I grasping for? Why go through the side effects and hassle of an intense regimen of cycles? There is no long term gain. Short term gain is a toss of a coin.

I will refrain from saying what I really think. I know many of you choose drug therapies and hold out hope. Some of you have had actual short-term benefit that made it all worthwhile. I wish you well.

I have excellent health coverage and live near my clinic. Another factor weighing on me, which is not directly related to my asking about the case for drug therapy, is that I am alone and must act as my own health advocate. I must do all the research of options, nudge my doctors to give useful, even if unhappy, information, and I must fight the bureuacracies. I am so fatigued it all seems like a battle.

There is dignity in death. I am at peace with it, but do not wish to bring it upon myself. Yet, why pretend to prolong the inevitable?

I seek your thoughts about my choices, all of them unhappy choices.

GaryV

[mausmish]

Hi Gary,

I can only speak for myself. I'm not a counselor or a health care professional of any sort. I'm a computer geek and crazy cat lady. I went through a similar thought process when I was diagnosed last January, weighing the known quality of life vs. the unknown potentials of treatment, including a lot of negatives. My doctors were pressing me to go for an immediate bone marrow transplant. Without treatment, my life expectancy was a reasonable ballpark 6 months. I wasn't feeling as bad as I should have, considering how low my counts were, but I was getting infections more easily and was running tired and very short of breath. My initial reaction was, "I don't want to die, but if that's what's going to happen, I can accept it peacefully." Quality of life is important to my husband and me. I was terrified of the prospect of a transplant. I opted to try Vidaza, which is similar to Dacogen. Fortunately for me, it began working with the first cycle and improved my quality of life a lot. All of my counts came into normal range within a couple of months and have mostly stayed there for the past 10 months. No more shortness of breath. No transfusions. Less fatigue. My platelets run a little low, sometimes hovering around 100, but before they were in the teens and twenties so 100 is good. I get the Vidaza via injection so my appointments are quick and easy. I've had minimal side effects (constipation, achy muscles for a day or two, a slight rash during one of the cycles). By summer, I decided to consider the transplant and went for consultations at several different centers to get different viewpoints. I also talked to a lot of transplant patients about the pros and cons. I am still afraid (terrified, actually, as is my husband) but I've decided to move forward, and in fact, will be getting a transplant the end of this month. I continue to feel great with the Vidaza treatments so it's very difficult to contemplate what the transplant will do to my quality of life. I decided to take the risk after hearing of so many positive outcomes and realizing that I wasn't as at peace with the idea of death as I originally thought. I've always believed that happiness comes in moments. I want to seize as many as I can. Obviously, each person must find their own path. Best of luck to you in your own journey, whatever you choose (and don't feel bad if you change your mind a lot of times along the way). I'm not a "group" kind of person myself but this forum is a great place to vent and to get as much or as little support and information as you desire, lots of super people here.

Karen

[Birgitta-A]

Hi GaryV
Like you I have not accepted any treatment except supportive therapy since dx May 2006. I have felt OK (no spleen enlargement) but during spring 2010 I needed blood transfusions (2 units) every week and my dysfuctional platelets were about 20.

My doctor persuaded me to try low dose Thalidomide and Prednisone for my fibrotic bone marrow June 2010. I was surprised and grateful when my platelets after 4 weeks started to increase (last count 76) and my HGB after 12 weeks increased so I have not had any transfusions for 8 weeks. No adverse effects when I take 4 caps Thalidomide á 50 mg/week and Prednisone 5 mg/day.

Vidaza has showed better treatment results than Dacogen. In this study 67 % of the low risk patients were blood transfusion independent and 73 % platelet transfusion independent:
http://www.eventure-online.com/event...ongressId=3446

In this study they look at response rate:

Previous LD AraC treatment, bone marrow blasts > 15% and abnormal karyotype independently predicted lower response rates.

Complex karyotype predicted shorter responses.

Low Performance status, intermediate and poor risk cytogenetics, presence of circulating blasts and RBC transfusion dependency ≥ 4 units/8 weeks independently predicted poorer overall survival.
http://www.ncbi.nlm.nih.gov/pubmed/20940414

You could try treatment perhaps with Vidaza - like Karen - that is the first line drug in MDS.
Kind regards
Birgitta-A
71 yo, dx MDS Interm-1 May 2006, transfusion dependent (142 units of packed red blood cells), Desferal and Exjade for iron overload, Neupogen 3 injections/week for low WBCs, Thalidomide and Prednisone for bone marrow fibrosis, asymptomatic

[Hopeful]

Hi GaryV,

Although you have an "excellent hemotologist", I am a firm believer in second opinions. Your case seems complex and deserves more attention as there may be more options.

In my experience, the doctors with a "passion for bone marrow failure diseases" will hold your hand more through the decision making process. Find one of them.

As to your question about "why drug therapy"...I believe that advances in research on bone marrow failure are happening at an accelerated rate. I hope to be here when a more definitive cure is discovered. If not, I would like to think that my experience has helped in some small way to the furthering of research for the benefit of future generations.

Never give up!

[Carole in Sudbury]

At the latest education day in Ottawa, we were told by the transplant doctors that when you are radiated in order to receive the transplant, you become sterile. Maybe your doctors have opted for drug treatment because of this.

[GaryV]

Originally Posted by Carole in Sudbury

At the latest education day in Ottawa, we were told by the transplant doctors that when you are radiated in order to receive the transplant, you become sterile. Maybe your doctors have opted for drug treatment because of this.

I can assure you that my becoming sterile is not a factor in making me ineligible for BMT. Sterility would be a small price to pay for an actual cure!

[GaryV]

Originally Posted by Hopeful

Hi GaryV,

Although you have an "excellent hemotologist", I am a firm believer in second opinions. Your case seems complex and deserves more attention as there may be more options.

In my experience, the doctors with a "passion for bone marrow failure diseases" will hold your hand more through the decision making process. Find one of them.

Thank you for your feedback. I didn't talk about the hand holding through the decision making process. There is sufficient touch, listening, and respect of my questions in the process.

I've been living with this for nearly 5 years. I have had second opinions. At this stage, about the only question that might merit a second opinion is whether or not spontaneous remission of transfusion dependence occurs with any frequency.

I have nothing against drug therapy. I believe Revlimid is not a good choice because I am not 5(q) deletion and my marrow is not fibrotic. Vidaza and Dacogen hypomethylating agents. Common side effects are anemia and low platelets. In my particular case, I am already critically low in those counts.

I do have other medical conditions. You say never give up. Choosing not to do drug therapy is not giving up. It is a viable option.

[GaryV]

Originally Posted by Birgitta-A

Hi GaryV

Vidaza has showed better treatment results than Dacogen. In this study 67 % of the low risk patients were blood transfusion independent and 73 % platelet transfusion independent:
http://www.eventure-online.com/event...ongressId=3446

[snip]

You could try treatment perhaps with Vidaza - like Karen - that is the first line drug in MDS.
Kind regards
Birgitta-A

Thank you, Birgitta. I find clinical trial results overall don't yet tell us much. The one you linked to showed good results. It is encouraged and raises hope in me, though, perhaps, no more merited than hearing anecdotal evidence on pineapple juice. I don't know.

Which leads to my question. You say that Vidaza is the first line drug in MDS. What is your source(s) for that? Why is it the case?

I read that in addition to being an MDS patient, you are a retired MD. Do you have any affiliation with any pharmaceutical companies? Do you receive speaking or any other fees from them?

Respectfully,

GaryV

[Birgitta-A]

Hi GaryV,
You know I am a retired psychiatrist and have nothing to do with any pharmaceutical companies - as a matter of fact I am very afraid of drugs due to the adverse effects.

There are not many studies of Vidaza in low risk patients - most studies with about 50 % improved patients were done in high risk patients - probably that's why the results are better in this study with many low risk patients.

Many reseachers report that for the moment Vidaza is the first line drug for MDS patients (except patients with the 5q- that often respond to Revlimid):
http://docs.google.com/viewer?a=v&q=...8ykxnGBZeG32MQ

Actually Dacogen is not approved in EU because they have not yet showed that the drug is better that best supportive care for high risk MDS patients. Probably that is because they have not tested the best way to adinistrate the drug. We all know that MDS is not one disease but many and some patients that don't respond to Vidaza improve when they get Dacogen.
Kind regards
Birgitta-A

[GaryV]

Dear Birgitta-A,

Thank you for your kindly response. I feared that my questioning your relationship to pharmaceutical companies might offend you. In the USA at least, doctors are in bed the Pharma in multiple ways. That influences what they recommend.

The article you provided cleared up a great deal for me. It says in its conclusion and elsewhere that "azacitidine is an attractive additional therapeutic option for patients with lower-risk MDS who are transfusion dependent and have failed other therapies."

I am transfusion dependent Intermediate I, so I have some insight into why my doctor recommended starting with decitabine.

Less seems to be known about decitabinethan azacitidine. Do you know any article on decitabine like the one you linked me to on azacitidine?

The significance of decitabine DNA-pathway versus azacitidine DNA and RNA pathways seem to be little understood.

Thank you again.

[Birgitta-A]

Hi GaryV,
It is quite OK to ask about affiliations - if you want to publish results in a medical journal you have to declare affiliations as you know.

I can't find any reports about Dacogen for low risk MDS patients. There were several abstracts about Dacogen at ASH 2009. Here is one: http://ash.confex.com/ash/2009/webpr...aper23691.html

Yes, the DNA and RNA pathways are very complicated. I read a very interesting article that I posted here some months ago but I can't find it now.
Kind regards
Birgitta-A

[JimK]

Hi Gary. Jim Kufis here.
I have been taking Revlimid (5mg every other day) for one year and it has worked wonders for me. I have been transfusion independent for the last year and I do not have the 5q- karyotype but do have an abnormal karyotype of chromosome 3. I think with Revlimid you can only try it to determine if it is going to work. Reports I have read indicate it works 25% to 50% of the time for patience that are not 5q-.

I have also read about Dacogen and Vidaza and it appears that Vidaza is the better choice. However, my Hematologist says that they are very similar.

With regard to a bone marrow transplant, I am 71 and I do not consider this a good option for me. If you are substantially younger, this is the best choice if you can find a donor that is good match. The procedure for the BMT is difficult but if it works it is worth it.

I wish you the best of health and know you will make decisions that are best for you.