Sunday, March 10, 2013

Saying No to Chemo: Non -Chemo Options for CLL, Part 1

This is probably the most common question that I am asked.

"I know that I need therapy, my CLL is taking off, but I don't want any chemo, so what are my options?"

The answer used to be "not much", but not so anymore. Today there are many choice and soon there will be even more.

But before I give my answer, let me give an important preamble and discuss what we are taking off the table when we veto the chemo option.

When fellow CLLers says no chemo please, I take it to mean that they don't want cytotoxic drugs that work by preferentially killing rapidly dividing cells.

For CLL in the USA, we are mostly taking about two classes of medications.

Number one and the backbone of most chemo cocktails is fludarabine that is a classic purine analog that kills by blocking DNA synthesis. Pentostatin and clardribine are similar adenosine analogs that work the same beat. What these cleverly designed drugs do is pretend to be purine, get themselves incorporated into the dividing DNA and completely gum up the work of replication. Nice.

The other class of pure chemo drugs we see a lot of are the direct descendants of the now banned World War I poison, mustard gas or nitrogen mustard. (The story of how its antileukemic powers were accidentally discovered is worthy of its own post). They destroy by attaching an alkyl group to any and all busy DNA, causing aberrant cross links and preventing it from making copies of itself. The more active the DNA, such as in a fast growing cancer, but also in our fast growing gut and skin, the more damage and the greater the kill. This is how the old standard therapy chlorambucil (AKA Leukeran) works. So too cyclophosphamide  (Cytoxan) the big C in FCR, and bendamustine (Treanda) an old communist drug but a new kid on this side of the Berlin Wall.

There are many many others cytotoxic drugs in oncology that play lesser roles in our disease such as vincristine (Oncovin), the V in CVP occasionally used for refractory CLL and just to confuse us, the O in R-CHOP used for Richter's Transformation and many lymphomas.

Oncologists carefully concoct these toxic cocktails with several goals in mind.

First they want to add to the killing power. Cancer is famously adaptive and will rapidly mutate itself right past a block on its road to lusty growth. Blocking it when it turns to either the left or right is a smart strategy. So too is capturing it in a pincer move with the lengthening lists of the toxic chemicals that make up the alphabet soup that we and others get IV to knock the socks off our cancer, and sometimes (but probably never in CLL) kill it for good.

But doesn't adding one drug on top of another inevitably lead to unacceptable toxicities?

Not necessarily so says our clever oncologists. They look for more than just complementary killing. They look for non-overlapping toxicities. CHOP is the poster boy example, a potentially curative cocktail for some lymphomas, where each of the chemo drugs interferes with the DNA in different synergistic ways AND where each drug has a different toxic target (the marrow or nerves or the heart).

Of course, it is never black and white, and dosing and individual sensitivities widely vary.

Hippocrates famously said that the difference between a medicine and a poison is the dose.

Never was this more true than with chemotherapy. Low dose oral chlorambucil is remarkably well tolerated, even in the elderly, but at the proven price of not doing much to extend the life of the patient.

Some chemo drugs are routinely used at low doses for relatively minor skin problems or auto-immune issues.

But the issue is more than the dose. It is also who is getting the dose.

Is there co-morbid heart disease or nerve damage from uncontrolled diabetes? Has the marrow been beaten up and is having a tough time rising again?

That is why it is so important that we stay well otherwise. Cancer is a hard enough fight without the handicap of a bad heart or bronchitic lungs.

Chemotherapy is not "targeted" in the strict sense, but it does preferentially cull the rapidly dividing cells and that is a good thing. In some cancers, it does such a strong job, it can cure. In CLL, while there are no chemo cures, it can and does give many of us years of healthy happy remission.

The majority of us that end up sitting in the infusion chairs for hours and hours report that while CLL chemo is annoying, it was much gentler that expected. No hair loss, little nausea. FCR or BR are wimpy protocols compared to some of the more potent stews used for more aggressive cancers. I know a surgeon who continue to operate all through his treatments with FCR.

Still cytopenias (low blood cell counts) are all too common including anemia, neutropenia with its high serious infection risk, and low platelets. So hand in hand with the chemo might come a partnering dose of a bone marrow stimulant for either red cells (EPOs), white cells (G-CSFs) or platelets (TPO mimetics) each carrying its own set of side effects and worries. Some of us even need transfusions to just keep going. More decisions. More risks. More time. More expense. More worries.

Long term, there also may be a price to pay. The marrow can only take so much before it gives up the ghost. When our marrow stops making enough of the three lineages of our blood cells, we are in dire straits and the only durable way out may be importing a new one AKA an allogeneic hematopoeitic stem cell transplant.

Chemo wallops our immune cells short term, risks of infections shoots up and may stays up for more than a year after fludarabine which is particularly nasty to our T cells.

Insist that your doctor offers you appropriate antimicrobial prophylaxis.

These drugs by design are mutagenic so we hold our breathe when we get our regular PAPs or mammos or PSAs or colonoscopies. We are getting them aren't we? Please see my earlier post on secondary cancers and do the right thing by yourself.

Infections and secondary cancers are the handle and the blade of the our grim reaper's scythe. So anything we can do to keep it reach short and its edge dull is good.

Eating right, exercise, love, sleep, and avoiding chemo are part of that prescription.

Still, when we face a clear and present danger, we must focus on our imminent needs and worry about tomorrow, tomorrow.

And until very recently, the best tools we had for staying alive when our cancer started to rage was a chemo cocktail, and I for one am grateful that these drugs were and are there in our time of need.

It was only a few years ago that we showed that for the first time a combination of chemo and immune therapy in FCR could prolong our lives. We know that those diagnosed with CLL in the 90s live longer than those diagnosed in the 80's, and much of the credit rests at the doorstep of chemotherapy and the modern management of its side effects.

So before we wave goodbye to chemo as some sort of poison concocted by the a cabal of international pharmaceutical companies, the military and medical industrial complex to keep cancer as a big profit center at our expense (believe me I encounter this line of thinking almost daily), let us calmly look at its risks and benefits.

Let's not throw the baby out with the bathwater.

If you have read any of my posts over the last few years, you have seen me vote with my feet and my blood. You know that I am a fan of the emerging small molecules and have tried to avoid chemo in my own personal journey.

All I am asking for is that we have some balance and keep our eyes wide open as we enter this brave new "post-chemo" world.

"Targeted therapies" while they might be compared a smart bombs or drone, they too like their battlefield equivalents, can pick off innocent target either that look like the enemy or are in the wrong place at the wrong time.

As I said, it isn't black and white.

More on non-chemo choices soon.

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Anonymous Anonymous said...

Hi Brian,
Thanks for this. Haven't updated you for a while but, as you know I was desperate to avoid chemo but ran out of options in January and started FCR as frontline treatment. Just finished my 3rd cycle and my specialists want to stop. I am having a bone marrow biopsy in 3 weeks to make sure I am MRD- which they think I will be. If not and depending how much cancer is left it the bone marrow they may proceed straight to allo or let me have whatever remission I get, while monitoring me closely and then go to allo when it returns. The problem for me with regard to the new TKIs is that I'm so young (love it that I get the be classed as young when I turn 40 later this year!). The transplanter has already had to transplant those who've relapsed on ABT 199 and fears that as good as ibrutinib looks this clever cancer of ours may become refractory to it - he cites Gleevec as not being the miracle cure while providing long remissions CML. The specialist leading the clinical trial on ibrutinib here in Australia has a different opinion. He would like me to have all 6 cycles of FCR and then when I do relapse (I'm unmutated with del 6q) go onto inbrutinib. He says if it eventually fails I will still be young enough for an allo and my sister is a perfect match. As my children are so young (8,6 and 3) I'd take the longest period of wellness possible - it's Chaya's classic Catch 22. I'm wary of having too much chemo - I feel great, have no palpable nodes and my bloods are perfect. I'm not neutropenic and would like to avoid heading that way. Am lucky that I'm unusual and have access to such great doctors (I just wished they all agreed on best treatment protocols for me!). Glad to hear all is going so well for you and thanks for all these videos. My very best wishes, Deborah in Melbourne

March 10, 2013 at 4:05 PM  
Blogger Shulamit said...

Thanks for your post. The NIH Ibrutinib trial I was hoping for was suspended just before I was to enter. With del 11q and needing treatment, I felt I had no choice but to go with FCR, since cyclophosphamide (the "C") is effective against the deleted 11q chromosome. It was heartening to see you refer to FCR as one of the "milder" chemo regimens, and indeed, I still have my hair (though it's thinner) and thanks to the anti-nausea meds, have suffered no nausea. But if I could have said no, I would have. Let's hope Ibrutinib and the other promising drugs are on the market soon, so next time around I can say no.

March 10, 2013 at 4:32 PM  
Blogger Shulamit said...

I am with you heartily on the wish to say no to chemo, but of course there are situations in which it's still the best (or only) option. In my case, with an 11q deletion and the hoped-for Ibrutinib trial at NIH abruptly suspended when I was about to enter, FCR was by far the best option: cyclophosphamide is particularly effective against del 11q. But it certainly does look as if the time will come when chemo will largely if not entirely be a thing of the past. Let's hope so.

March 10, 2013 at 6:21 PM  
Blogger Kreale said...


I enjoyed reading your recent post. I am curious to know if you have an opinion regarding the consumption of apricot kernels to cure/control cancer. I realize there is controversial data on this topic and would love to hear your perspective.

Kind Regards,


March 10, 2013 at 7:16 PM  
Blogger Beverley Paine said...

Thank you Brian, for your easy to read and digest summary of the situation we face thinking about treatment.

March 11, 2013 at 2:20 AM  
Anonymous Anonymous said...

Hi Brian, Thank you for your posts. I was diagnosed with SLL/CLL Dec. 2010. Have refused chemo (FCR & BR) since then. I have 17p deletion. Lost out on Ibrutinib trial May 2012. Started eating apricot seeds June 2012. You can see my blood chart at
Since June 2012 to March 2013 my WBC has dropped from a high of 18.2 to 6.1, and ALC has dropped from 8.7 to 2.6. I am wondering what you think. I feel great, and am hoping that my platelet count will start moving up soon.
Thank you again for the time you take writing your blog.

March 11, 2013 at 6:53 AM  
Anonymous Deb Light said...

Great post and thanks for making these chemo choices easier to understand.We appreciate all your time and effort to help all CLLer's.You are truly an Inspiration to all.Look forward to reading part 2.

God Bless,

March 11, 2013 at 9:20 PM  
Anonymous Anonymous said...

Well said, Brian!

The 6 preceding comments demonstrate the dilemmas that we all face in making choices on the therapeutic yellow brick road.

Rick Zelnick

March 12, 2013 at 5:02 AM  
Anonymous Anonymous said...

Great post. In my 4 years as a CLL patient, I have never heard of apricot kernels. I did some googling and came up with this from webmd.

Apricot kernel is the inner part of the seed of the apricot fruit. The kernel is used to produce oil and other chemicals used for medicinal purposes.

Despite serious safety concerns, apricot kernel is used for treating cancer. It is taken by mouth or given as an injection.

How does it work?
Apricot kernel contains a toxic chemical known as amygdalin. In the body this chemical is converted to cyanide, which is poisonous. There was interest in using apricot kernel to fight cancer because it was thought that amygdalin was taken up first by cancer cells and converted to cyanide. It was hoped that the cyanide would harm only the tumor. But research has shown that this is not true. The amygdalin is actually converted to cyanide in the stomach. The cyanide then goes throughout the body, where it can cause serious harm, including death.

Also, is a pretty good source. As Dr. Hamblin used to say, "The plural of anecdote is not evidence."

March 12, 2013 at 2:55 PM  
Anonymous Anonymous said...

3 cycles of FCR and my BMB has confirmed I'm MRD negative. Hoping for a decent remission now despite the poor prognostic markers. Bloods are completely normal and I worked all through treatment. For younger and healthy patients I still think chemo shouldn't be discounted altogether. We have many years ahead (fingers crossed) with this disease and there's plenty of time for the new drugs to come down the pipeline. Don't discount FCR altogether - I was terrified of having it but was lucky, had no side effects and it has put my aggressive CLL to bed for the time being. Good luck to everyone out there. Deborah in Melbourne

April 3, 2013 at 2:51 PM  

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