Saturday, March 15, 2014

ASH 2013: Dr. Jeff Sharman Discusses FCR versus BR in Front Line CLL

In this interview, Dr. Jeff Sharman gives us some understanding of the important trial data presented at ASH 2013 that compares FCR (fludarabine, cyclophosphamide, rituximab), the gold standard chemo-immunotherapy (CIT) to BR (bendamusine-rituximab) the new kid on the block and very popular with community oncologists.

In the excitement and promise of the new era of gentler and more effective oral medications for CLL, there is still a diminishing group of patients that for many reasons will continue to chose a chemo-immunotherapy (CIT) approach.

One possible reason is that for a few patients with excellent prognostic factors, a significant subset of those will reach MRD negativity and for that group FCR produces exceedingly durable remissions, starting to hint a possible cure. A half year of harsh but not the worst therapy, and you're done. Time to get on with your life without any daily pill reminding you that you have CLL.

Professor Hallek discusses this special group in my short interview from iwCLL last year.  I would not be completely dismissive of the value of CIT in those special circumstances.

Sadly insurance coverage and expense will be another reason that we will still see chemo. Older drugs are cheaper than newer drugs.

And even more sadly, patients' and physicians' unawareness of the rapidly changing therapeutic landscape will limit some of us CLLer's option to what our oncologist is most comfortable with it.

A few of us won't be able to tolerate the new oral therapies due to side effects, but as more options and new TKI's are approved I suspect that will be a vanishing small number. There are also the very few patients who have progressed on ibrutinib (the only oral TKI approved for CLL at this time and available by prescription) and an unfortunate group of us who both can not qualify for a trial or who have no access to the new meds because of where they live or their insurance and who need treatment NOW and can not wait for a different option.

That said, the FCR versus BR data welcomed as it is, is hardly the blockbuster news that it would have been a few years ago.

Ibrutinib and idelalisib and ABT-199 and obinutuzumab and others have rightly stolen the spotlight at ASH and elsewhere. Their time has come, and not a moment too soon.

Still CIT is not going to quietly fade away so fast so let's look at this important ASH abstract.

This link gives the data.

This link explains what is meant by the grade of adverse events and reminds us that a grade 3 adverse event is severe or disabling, a grade 4 is life threatening and a grade 5 adverse event is polite medical talk for a side effect that kills the patients. So when we see that on the FCR, we patients had a 90% of a Grade 3 or worst hematologic side effect compared to only two out of three in the BR arm.

The price of this higher that high toxicity and small but real risk of dying from FCR was an impressive 98% overall (ORR) response rate with nearly half of those being CR (complete responses). With BR the ORR is the same but the CR is 38%. MRD (minimal residual disease) negative data was not presented. Progression free survival was better for FCR in those under 65 years old, but not in the older group.

So very impressive results, but significant toxicity. This is an old and too common story with chemo: The more toxic the drug, the better it works. FCR is better in younger patients, but comes with more risks and misery.

New targeted and biological therapies break this paradigm and that is why when we have a choice, we should be putting the emerging therapies high on lists of options.

Remember too that this trial was for front line therapy in fit patients where access to the newer treatments in even more difficult.

Listen to Dr. Jeff Sharman and get his take on this important study. Dr. Sharman is a smart, very busy and compassionate guy who has done much to help the CLL and other blood cancer community and I am grateful for the time he gave for this interview at ASH 2013.

Dr. Sharman has an excellent blog himself where he covers much of the same and even more detail on the trial here.

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Friday, March 14, 2014

The Good Cancer

Here is a post I wrote in response to a spirited discussion in a CLL forum on the topic of how we patients are informed about our diagnosis and the unnecessary anguish called by sometimes well meaning but poorly informed and of touch physicians. As is everything in CLL, it's complicated and clear and sensitive doctor- patient communication is the starting point for a good outcome.


CLL is too often still called the "good cancer" and all of us CLL patients rightfully hate that.

No cancer is good. But perhaps the problem is more with the word cancer than the word good.

We are pleased when our doctors tell us that we have the "good" prognostic factors, knowing full well that guarantees nothing about our future.

We are happy to see a "good" lab result,  knowing full well that it might change tomorrow.

Cancer is such a loaded and malevolent word that the idea of putting something positive in front of it carries a similar horror and disbelief that would accompany  anyone uttering a phrase such as: it was only a "gentle" abuse or a "polite" hijacking. There are worse oxymorons, but I'll skip them.

Doctors want a short hand to say we have good news and bad news. There is never an excuse for poor doctor-patient communication, but we all know it is often going to be a short communication.

Many patients don't know what indolent means until well after they have been diagnosed, and to say slow growing, many patients might only hear the "growing" part especially when it is qualified with the adverb, "usually".

Let's get some perspective.

CLL is not an imminent death sentence, especially now. A significant chunk of us will never need treatment and even more of die with the disease, not from it. Nearly all of have some real time to rub our chins, plan our lives, and consider our options before any therapy is needed. And if and when treatment is eventually needed, today we have a load of non-chemo therapies available and the floodgates of less toxic choices are just starting to open. 

Maybe the cancer isn't good, but all of this is good. Very good!

Ask most patients with pancreatic cancer or MDS  or glioblastoma multiforme or metastatic ovarian cancer if they would want to trade their cancer for ours. Ask any doctor which bad news he prefer to share with his patient. It is easier to say someone has a bad cancer than a good one.

Moreover, doctors want their patients to have realistic expectations, good or bad. There are documented tragic cases of elderly patients committing suicide when they found out they had CLL because they thought it was quick death sentence. It is incumbent on any health care worker to offer comfort always and hope where hope is a real possibility.

Finding the balance is so hard.

I am trying to think here as both a doctor and as a patient. What do you think if you heard this as a starting point from your doctor?

"You have CLL, a chronic form of a blood cancer. (Pause…) While all cancer is bad, some are much worse that others. Now I want you to listen carefully to what I am about to say. (Another pause...)  While no-one knows the future, CLL is most often, not always, but most often, one of the least aggressive kinds of leukemia".

That takes longer than saying you have the "good cancer" but not too much longer. And there are a millions other ways it could be said better. And that is just the beginning of a much longer discussion to come. 

Tough stuff. Whole books on medical ethics and patient communication are written on this topic.

These and similar and usually much easier issues are what I struggled with everyday as a doctor turned patient.

Stay strong

We are in this together.


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Wednesday, March 12, 2014

Pills, Pills and More Pills: A Follow-up

Seems as if my last post on too many pills struck a nerve.

According to some of the feedback that I received, I am way out of my league with my complaints about my pill count. Some of us patients top 85 pills a day.

Here is an important email that I received from one of the readers of my blog who makes some good points that I thought I should share.

A few years ago I had to take about double the number of pills I take now.  I simply adopted the view that for every new medication I was asked to take, I asked the doctor to find two that I really didn't need.  The strategy seems to be working.

I developed this strategy after contemplating something my mother went through years ago.  She was taken to the emergency ward of a local hospital.  She was very sick from a number of things and death was imminent. Her organs started to fail.  It was decided that they would keep her pain under control but stop all other medications and allow life and death to take their course.

Once they stopped ALL of her vast amounts of medications (once on a med she never got off it) and she immediately began to recover.  In fact, she lived for 12 more years after that incident.

Of course you are a doctor, but for the rest of us I would suggest that twice a year (or more often if required) each of us present a full list of our meds to each doctor that treats us, with a view to stopping all meds that are no longer needed for one reason or another.  Doctors seldom have a list of the meds they have prescribed to us over the years and some doctors don't bother, of their own initiative, to even review those meds, let alone reviewing all of the meds we are taking in order to take out meds that are no longer necessary.

These are important lessons here. 

With today's larger integrated healthcare delivery systems for outpatient and inpatient services and the possibility of a shared electronic medical records, it should be easier to keep the medication records up to date, but as a dear friend can testify when his wife recently came home from hospital on two nearly identical meds (the second one was completely unneeded and a potential problem), it is still too often the case that care is not co-ordinated and patients are taking drugs  that at best they don't need, and at worst, can be dangerous.

That is why is important to be our own well informed advocates.

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Monday, March 10, 2014

Pills, Pills and More Pills: A Serious and Sometimes Humorous Look at Adherence

I have blogged extensively on the serious problem with adherence with oral cancer medications in past posts. Check out my interviews from ASH 2013 if you haven't seen them before.

Pills don't work if we don't take them.

Many factors play into how faithful we are about following our doctors' and pharmacists' orders.

Let me get personal.

I need to take way too many medications. And with way too many twists and turns in how they are taken.

It is so bad that when I travel, I carry a note from my doctor so I don't get stopped by security for all the pills and potions, many of which are unlabeled including the precious unmarked grey capsules that form my trial supply of ibrutinib.

How many pills do I take?

I take so many pills that I could skip breakfast and still have a full stomach.

How many pills do I take?

I take so many that the pharmacy asks me if want help carrying my prescriptions to the car.

How many pills do I take?

I take so many pills that I could reproduce a decent pointillist copy of Seurat's A Sunday Afternoon on the Island of LA Grande Jatte with a week's worth of the medicine in my bathroom.

OK, I am exaggerating, but you get the idea.

My carry on is mostly drugs, both my regular daily doses and my "just in case" meds.

Let's start with the "emergency" meds first.

I always travel with Levaquin for respiratory infections, Cipro for all other bacterial infections, and Tamiflu for influenza. These are like my talismans used to ward away the very infections they are designed to prevent. I cling to the magical thinking that if I bring them, they won't be needed, and if I don't, then watch out.

The magic has worked so far. My same old box of Tamiflu has been irradiated by airport security around the world 100s of times by now.

I may bring ginger and meclizine for nausea and also Imodium and Culturelle (a probiotic) for diarrhea when I travel to exotic lands, topical voltaren, arthritis-acetaminophen, Celebrex, and a few very old stronger pain pills just in case. Over the counter Pepogest (peppermint oil) is my go to for most GI issues.

I don't bring anything for sleep or anxiety. I am lucky that way.

I do bring herbal teas with mullein, slippery elm, and marshmallow root in case I get a sore throat or hoarse voice when I am scheduled to speak.

I pack several cold and allergy remedies too for my longer trips out of the country. Otherwise I can just buy them as needed.

I bring a whole different list of meds for my wife when she travels with me.

My regular daily meds overflow their AM and PM plastic pouches. And when I travel more that 10 days, I need large two pill cases. And I always take at least three extra days of everything.

Getting my meds ready for travel is a more time consuming, exacting and high stakes chore than packing my clothes or my paperwork.

At home or on the road, the daily routine is killer too. I am thankful that I don't take any mid day meds, but in the morning I have ibrutinib 1/2 hour before eating or taking all my other meds. Those include one that I must remember to take only three times a week and one sublingual that I wait to dissolve under my tongue just once a week, and finally one where my dose is variable depending on my activities that day. One must be taken daily after  the same meal daily. One is pill is cut in half and another one in quarters. This all takes a ton of time.

The cyclosporin that is a twice daily medication comes in a bulky thick foil individual wrapper that defies my feeble fingernails in their bumbling attempts to open the packaging, so I often need to cut out each individual capsule. But scissors are a no no in carry-on, so I always bring extra cyclosporin when I am on the road (or in the air)  in case I can't open some of the packets. And what's worse is that me being a vegan and having to gulp down so many capsules made with gelatin, an animal protein obtained by boiling skin, tendons, ligaments, and/or bones with water. 

I don't want to even think about it.

Another complication is that a couple of my regular supplements must live in the fridge. They get forgotten the most. (Left out in the cold)

Another is a tart and fizzy powder that is mixed with first hot water and then cold water, twice a day.

I haven't mentioned all the topical creams my dermatologist wants me to use and the ophthalmic ointment needed nightly to prevent painful corneal abrasions that I self apply with a mirror and a flashlight and that effectively blinds me throughout the whole night.

Until the parade of pills starts all over the next day.

We can understand why oncologist like infusions. They can be sure that the precious medication is delivered.

Still, I am grateful that these oral and self administered medications exist, that I have the insurance and resources to afford them, and the freedom and health to complain about the whole twice daily rigamarole.

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Sunday, March 9, 2014

The Sad and Untimely Death of my dear Friend Dragana: "Dying for Your Principles" or "Herbs versus Cancer is a Fixed Fight"

2011 in Wales
Dragana is wearing the red skirt

If tragedy is suffering without meaning, then I am trying to give meaning to the untimely death of this  beautiful woman on March 6, 2014. Please follow with me as I share the story of how our intertwined paths unfold. There is even a poignant cameo appearance by the late Dr. Hamblin.

I first met Dragana on her 40th birthday in the magical kingdom of Bhutan in 1997, and I last saw her over two years ago though we Skyped often until a few weeks ago.

Let me linger on our first encounter seventeen years ago to place out connection in the exotic, mystical, and Eastern space where it flourished for so long.

Went we met in the land of the the peaceful dragon half way around the world, my best friend, Todd and I were traveling to celebrate his 50th birthday to escape all the "Depends and Geritol" jokes and instead spend his half century mark visiting as an exotic place as possible.

Those days, the Buddhist kingdom of Bhutan was not receiving too many tourists (still isn't), especially in the monsoon season when we slipped and slid around in the thin air on the narrow and muddy Himalyan roads, but what it lacked in creature comforts it made up for in the beauty of the people and their country.

Then there was no TV and no lawyers, the national sport was archery, polygamy was common, and everyone wore the traditional clothing of a "go" and argyle socks and spoke the queen's English. As a potency talisman, there were pictures and sculptures of erect ejaculating penises everywhere hanging from rafters in people's homes, inside Buddhist temples and on the walls of government buildings. We drank yak milk and ate red rice. We never encounter a Yeti, but he and she can be found commemorated on the country's stamps. Wedged in the Himalayan mountains and valleys between India and China, Nepal and Bangladesh, the citizens proudly say it would be the largest country in the world if you could iron it out. 

The modern basketball loving king famously wants his government to increase the country's gross national happiness. Check out his website for the details.

It is also known since ancient times as the land of medical herbs. 

That is where Dragana fits in.

Dragana was part of a small ex-pat community working in the capital, Thimphu, as a third generation herbalist for the government helping to modernize traditional Buddhist herbal medicine.

She was standardizing and identifying active agents, checking for bacterial and fungal contamination, and cataloging ancient therapies.

She proudly told me that she brought the first elevator to the country, actually a dumb waiter to deliver the bulk herbs to the traditional hospital.

She was melding modern technology and science with ancient wisdom, something she was expert at.

Her knowledge of botanical and traditional Chinese medicine, her amazing talent as artist painting the plants that she so loved, her creative approach to raw organic vegan food, her dizzying personal energy, her ruthless ability to see though my sometimes facile notions, and her complete commitment to her herbal way of life has been a beacon in my life. 

We stayed in touch, at first by handwritten letters, then email, then phone and finally Skype. Though she was born in Croatia, she called England home and worked as an herbalist for Neil's Yard, a respected maker of various botanical products. My son Will once helped her pick wild lavender for one of her concoctions.

We met again in Spain when I was traveling with my same friend and my oldest daughter. I visited her twice in England, once with my two boys and yes the same friend (Todd and I have traveled a lot together), and the last time with my wife.

I remember us standing together in remote Druid stone circles in the rain at midnight or exploring the English country side for wild herbs and flowers or lounging in the sum In Parc Guell in Barcelona.

She visited the US with her friend Daphne (pictured above on the left) to attend my daughter's wedding and three of my four children visited her and stayed at her home in England. Just a few months ago, Dragana arranged for my oldest son to visit at last June's summer solstice celebration with the Druids at Stonehenge.

When she came here eight years ago for my daughter's wedding, she was one of the very few that I told of my cancer diagnosis one month earlier. She and Daphne immediately deconstructed my diet and my life, helped me shop for a juicer and order all the accruements of my new raw vegan lifestyle.

She had little faith in Western medicine, but I am proud that she would occasionally and reluctantly consult me on allopathic matters when her herbs were not strong enough.

When I visited her last, she had been diagnosed with cancer. I scheduled a trip to England to beg her to consider a likely life saving and curative surgery but she would have none of it. She came into the world with all her parts and she was leaving it the same way. We even all visited the wonderful CLL champion Dr. Terry Hamblin not long before he passed on from his colon cancer. (Dragana was in his living room with us in the picture from my memorial post). I had not prepped him in anyway, but somehow he came to tell us the story of how early in his career as as an oncologist he had had a patient that refused curative therapy for her cancer because she wanted to treat it naturally. She went on to die a needlessly horribly painful death from metastatic disease. I was moved by the story, but Dragana was not. She heard none of this. In fact, she felt sad for Dr. Hamblin and his sterile English diet and his trust in Western medicine.

She also heard none of my pleas to be open to all possible options to cure her cancer. She was clear and strong on this.

Instead, my wife and I traveled with her though southern England and Wales and had a marvelous time. 

Near the end, the terrible pain of metastatic disease caused her to relent. Palliative radiation bought her respite to revisit her home in Croatia. Hospice care with pain meds made sure she was comfortable in her last few months. Even then, when she was so weak that she could barely speak, she still refused most therapies and used her herbs to ameliorate many of her symptoms.

She lived and died in a consistent and valiant way, congruent with her whole life's work and philosophy.

Now she's gone and I will miss her powerful and haunting spirit. She opened my eyes to a bigger world and changed my whole approach to food and herbs and really healing. She also became a dear friend and mentor to my whole family.

I am so sad that she's passed and I so wish that I could have changed her mind so that I could plan another visit to her home in the beautiful English countryside to learn from her and to eat one more of her amazing meals. I want to chat on SKYPE with her tomorrow and get her counsel on diet and herbs while she scolds me on my out of balance life choices.

There is a huge part of me that is in shock that I have outlived her. My cancer is still for the most part incurable. Her's was not.

Even if I wish it wasn't so, I respect and admire her decision.

My backbone is less strong. Though I hate chemo, if there was a chemotherapy available tomorrow that would for sure cure my CLL, I'd be first in line. Heck if it was proven homeopathy, which in the face of it seems completely nonsensical, could get me a lasting remission, I would give it a try, even if meant standing my whole allopathic understanding of medicine on its head.

I believe we need to use what is proven to work, and when that is unknown, which is too often the case, we should use what makes the most sense to our hearts and our brains.

But I also believe we need to be open to change, especially radical change, as Dr. Hamblin would say, "think laterally".

The Talmud teaches we are to live by the commandments, not die by them. I generalize that principle to be pragmatic core of my flexible approach to healing. I am results oriented. Dragana was process oriented, committed to a balanced and "eastern" way of seeing the world. If and when our we ever meet again, I am sure we would lovingly disagree on who chose the better path.

In the meantime, I cherish the nearly seventeen years that she was my dear dear friend.

Every time, and this would be many times every day, that I eat a sprouted grain or drink a raw vegetable juice or thumb my nose at a GMO highly processed food, I will think of her.

Rest in peace, Dragana. You are a very special person.

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