9 replies to this topic

[scuba]

I received my lastest (October) PCR test result without any TKI for nine months. No change. Holding steady at PCR = 0.06% IS scale.

 

I started my cessation experiment last February when my PCR was undetected. PCR rose into detection but then fell back. It rose again and is now hovering at this level for a couple of months. I had expected relapse to be much faster than this if it is going to occur, but thankful I have had nine months of no Sprycel. 

 

Because I am still below MMR, Dr. Cortes is fine with me going another month without Sprycel (20mg.). My experiment continues.

 

This next month will be definitive, however. If my PCR level remains the same, I will re-start low dose Sprycel anyway to test how quickly I can drop PCR back down again (one log drop). If I can do that, then I will pursue a pulse strategy of one week on - three weeks off. Although I had hoped I would be able to maintain low level residual at a fairly constant level without any TKI, I sense that I might have to "pulse" treat CML. Hit it to knock it down and then no drug (I do believe it is the Curcumin which is keeping CML expansion slowed - but not stopped as far as I can tell. I have one more month to see).

 

My bet with Trey was for one year. I'm almost there, let's see if I can keep this experiment going.

[Frogiegirl]

All I need is 9 months to sneak by to have my last little one. ....you give me hope scoobs!!!!!! I think the pulse therapy is a good option as well. ...but does that leave more room for mutations? ???

[Buzzm1]

Congratulations on remaining below MMR, since stopping Sprycel 20mg in February, Scuba.  

 

At 0.06% IS scale, it's hard to call it a relapse .. 

 

Buzz

[rcase13]

My onc still thinks there is a risk with mutations or resistance with low doses of a TKI. He prefers a patient stop the TKI completely rather than do a low dose approach. He prefers full dose unless low blood counts prevent it.

The theory is the body at low doses has a chance to develop the resistance whereas at full dose the body doesn't have that chance. Basically the same theory when we take antibiotics.

Not that it matters as I am not near undetectable. But it makes sense to me. I prefer full dose so I can beat the sh%t out of cancer.

[scuba]

My onc still thinks there is a risk with mutations or resistance with low doses of a TKI. He prefers a patient stop the TKI completely rather than do a low dose approach. He prefers full dose unless low blood counts prevent it.

The theory is the body at low doses has a chance to develop the resistance whereas at full dose the body doesn't have that chance. Basically the same theory when we take antibiotics.

Not that it matters as I am not near undetectable. But it makes sense to me. I prefer full dose so I can beat the sh%t out of cancer.

 

Your doctor is confusing bacteria with cancer. Think about it this way. How did they determine full dose for a TKI? I mean why is 100mg Sprycel the full dose? Why not 200mg or 400mg? It is because beyond 100mg, patients exhibit toxicity and can't tolerate the dose. Many patients can't even tolerate 100mg without all sorts of bad side effects. I could not tolerate 70mg. But 20mg. brought me to PCRU. Prior to my cessation trial, I was on 20mg for years.

 

Clinical trials are all about how much can we pump in before bad things happen. The idea being "more is better" in attacking the cancer. And we all know that more is better is not necessarily correct.

 

In the case of Sprycel - it's half life is five hours. This means that most of the time, your body has little TKI fighting the cancer. But it works. Why?

 

It's a problem in dynamic equilibrium. If there is sufficient TKI to decrease the CML population greater than the CML population increases, then there will be a net decrease. And over time this can lead to long term remission. The dose required to maintain that remission is patient specific. In some patients the dose is greater than the toxicity - which means the drug doesn't work for them. But for others, the dose is much less than toxicity and they are able to achieve great results.

 

Mutations happen either from instability in the DNA or an outside ionizing event (radiation). Mutations happen all of the time. 

 

You prefer full dose - I prefer no dose. Interesting that both work.

[Buzzm1]

Sprycel efficacy, from what I have read, appears to be slightly superior to Gleevec, in the amount of time taken, on average, to reach MMR and CMR..  I'm wondering if that efficacy also applies to the depth/length of remission?

 

I'm over 4 years PCRU on Gleevec, and beginning today, will have further reduced my dosage down to 150mg.  Hoping to learn more about the efficacy of the newer TKIs as time progresses and more studies are done  ... wouldn't hesitate to switch over to a low dosage of one of the newer TKIs if it meant a possible deeper remission, and a lower probability of a relapse after cessation.  I test again again tomorrow so right now, for me, it's all about maintaining PCRU,  one test at a time.

 

Buzz

 

still hoping to make a comeback

[Buzzm1]

following up with a little research: http://asheducationb...2013/1/168.full

 

A recent French study assessing the molecular disease recurrence rate in patients ceasing second-generation TKI therapy after achieving stable deep MRs was encouraging. Patients who switched to nilotinib or dasatinib because of intolerance to imatinib and then achieved stable CMR had a 60% probability of remaining in remission off therapy.27 Given that the achievement of deep MRs appears to be higher with second-generation TKIs than with imatinib, the overall rate of treatment-free remission achieved using nilotinib or dasatinib frontline may be significantly higher than the 15% who can achieve it on imatinib (Table 2). On this basis, we can conclude that, on the balance of probabilities, it is likely that second-generation drugs used frontline will achieve a higher rate of treatment-free remission overall. However, more mature data are needed before we can say that the case is proven beyond reasonable doubt.

[Gail's]

Thanks for the research buzz

[mdszj]

Scuba

 

You said: "Mutations happen either from instability in the DNA or an outside ionizing event (radiation). Mutations happen all of the time."  I thought I saw at least 1 paper a while back indicating that turmeric/curcumin helps to protect genes and DNA from further cancer causing mutations.  Was wondering if you know anything about this and if you think the curcumin is helping against that.

[scuba]

Scuba

 

You said: "Mutations happen either from instability in the DNA or an outside ionizing event (radiation). Mutations happen all of the time."  I thought I saw at least 1 paper a while back indicating that turmeric/curcumin helps to protect genes and DNA from further cancer causing mutations.  Was wondering if you know anything about this and if you think the curcumin is helping against that.

 

Turmeric/Curcumin has documented anti-cancer properties:

http://www.ncbi.nlm....les/PMC2914279/

 

But like anything involving trillions of cells - some bad cells are bound to escape. Curcumin is not a cure. At best - it slows cancer down and in early stages may even enable our natural defenses and repair mechanisms to take over. My own view is that Curcumin works alongside TKI's () to help them be more effective at doing their job. We don't have enough data from trials to say one way or the other on Curcumin. 

 

Should a new mutation occur - it's possible that Curcumin may help check it. But without full clinical trials we will never know. 

 

Is Curcumin helping? I believe so - otherwise I wouldn't be taking the stuff.