Remission

Words are powerful things, they have the power to convey intense feelings and to mark periods of profound significance.  I've recently been pondering the meaning of a new favorite word - remission.  Definition:  A period during which symptoms of disease are reduced (partial remission) or disappear (complete remission).  Disappearance of all disease is complete remission; reduction tumor size by more than 50 percent is considered partial remission.
   As of last week it was confirmed that my tumor load continues to go down, over 60% and probably closer to 75% and slowly shrinking.  My fantastic results from last restaging at Moffitt (scans to check my tumor progress) have been confirmed.  Wait a minute - I think I smell some success around here!  Not complete remission or NED (no evidence of disease) but as close to that as I'm likely to ever see.  Some of my tumors have turned into hard little masses that are floating around my innards like little dead soldiers on a battlefield.  They are not bothering me, and maybe they will scare off any other cancer that might start getting ideas.  My little tokens of victory.
   The BRAF/MEK combination is working - has worked - and I'll stay on it indefinitely.  Side effects are minimal, prospects are good.  I get sick sometimes from the meds but I know it is the meds and not the cancer making me sick and that helps me tough it out.

   So let me take the time here to thank all of you for following my journey.  I acknowledge it is not over yet - there is no cure for cancer.  My remission may not last, no one has been on this drug combo for over a year so we are in unchartered territory in terms of long term results.  I could start rejecting the medication.  I could get hit by a bus tomorrow or abducted by aliens.  I'll just group all of that into a pile of things I don't want to happen to me and move on with my amazing life.
   I remain sad only over the intimate knowledge that I now have of the suffering of others with this disease.  I know the fear, the humiliation, the pain and the loss that invade the lives of cancer patients.  Multiply that times 20 million and it is almost soul crushing.  Dickinson said "Success is counted sweetest by those who never succeed" and its those that take the sweetness somewhat out of it for me.  But I have survived and I will continue to fight for those who cannot.
   I'm not sure what I'm supposed to call myself now, "cancer survivor" or "living with cancer" or something else.  I'm supposed to be creating a "new normal" and start dealing with the survivor guilt I feel for those fellow warriors that have fallen in the past year.  Those unfortunate enough to not have the BRAF mutation or good health insurance or a lucky choice of oncologist.  I'm supposed to find meaning in all of this, but all I want to do is breathe, remain calm and carry on.

But right now I will heartily enjoy sending a very loud and very intense "fuck you" to cancer.  You picked the wrong body to invade this time and I have thoroughly enjoyed watching you die.  To all of cancer out there I repeat one thing very clear that has been on my lips since day one, the mantra I repeated over and over again those long nights in the hospital, the words I said a million times waiting for the doctor to come in the room with results or watching chemo crawl through an IV into my arm - not me, not now.  No way, cancer.  Not me.  Not now.

Bad news, more good news

Bad news first - another fellow fighter has fallen.  Jake, author of the excellent blog Jake's Take - succumbed to the disease last week.  Jake and I both went through the TIL procedure around the same time and both had negative results and have been going through many of the same things over the past year.  My thoughts go out to his wife, children and family.  Jake set the bar for humor, strength and humility.

For the good news - continued success with the combination therapy.  News of this has hit the press from the ASCO conference.

Glaxo Melanoma Drugs Beat Standard Chemotherapy In Study

BLOOMBERG - By Makiko Kitamura and Robert Langreth - Jun 4, 2012 12:00 AM ET

Two experimental GlaxoSmithKline Plc (GSK) drugs that block genes tied to lethal skin cancer worked better than chemotherapy in studies that tested them individually, paving the way for final-phase trials on their use together.

About 80 percent of patients with advanced melanoma given Glaxo’s trametinib were alive after six months, compared with 67 percent on chemotherapy used as a standard treatment. Separately, Glaxo’s dabrafenib delayed disease progression by 5.1 months, compared with 2.7 months for chemotherapy. The Glaxo-funded research is being reported today at the American Society of Clinical Oncology meeting in Chicago.

The individual research followed an early-stage study in 77 patients that found the drugs used together resulted in fewer skin lesions than previously reported with Roche Holding AG (ROG)’s Zelboraf, a therapy cleared last year that targets a mutant gene found in half of advanced melanoma cases. Glaxo has begun two final-stage trials on the combo therapy, the company said.

The combination “is where we have the most enthusiasm right now,” said Keith Flaherty, director for developmental cancer therapeutics at Massachusetts General Hospital in Boston, and an author on the trametinib study. It “looks better in terms of efficacy, and better in terms of safety.”

The U.S. will have an estimated 76,250 new cases of melanoma this year, with 9,180 deaths, according to the National Cancer Institute. While patients with early-stage disease respond well to treatment, the five-year survival rate for those with cancer that has spread is 15 percent, according to the American Cancer Society.

Billion-Dollar Drugs

Approval of the two Glaxo drugs could generate as much as 1.5 billion pounds ($2.35 billion) in 2020, said Andrew Baum, a London-based analyst at Citigroup Inc., said in a note to investors last week. The company will seek regulatory approval of both compounds individually later this year.

In an interview, Paolo Paoletti, president of the oncology unit for London-based Glaxo, said his company has begun two late-stage trials of the combination therapy in advanced skin cancer. One will compare the combination to dabrafenib alone; the other compares the combo to Roche’s Zelboraf.

“We are rolling; the interest is so great the enrollment will be very quick,” said Paoletti. If the benefits of teaming the two drugs hold up, “it is a transformation. It will be a new standard of care.”

Zelboraf and Glaxo’s dabrafenib work by blocking BRAF, a mutant gene that spurs cancer cell growth in about half of melanoma patients. Zelboraf was approved in the U.S. in August 2011. Trametinib is designed to thwart a related protein called MEK that helps tumors resist an assault on BRAF.

‘Gold Standard’

With few side effects, the combination therapy could become the industry “gold standard” in treating melanoma patients with the BRAF mutation as early as 2014, CitiGroup’s Baum said.

One downside of the BRAF-blocking drugs is that using them may activate certain growth pathways in healthy cells, leading to non-melanoma skin cancers. Adding the MEK drug can block the formation of these skin lesions, it turns out, Flaherty said.

Finding out that a second drug can cancel out the side effects of the first “was the cool part,” Glaxo’s Paoletti said. “Usually, when you combine two drugs they increase toxicity.”

Glaxo’s move into combination trials was “so gutsy,” said George Demetri, an oncologist at Dana Farber Cancer-Institute in Boston. “Glaxo did a spectacular job.” Demetri said he was a scientific adviser for one of Roche’s partners in the development of Zelboraf.

Good news! Good news! I repeat, Good news!

actual microscopic image of my BRAF+

MEK being delivered at a cellular level
(my white blood cells wear body armor!)

I was just restaged last weeks after six weeks in the clinical trial on the combination targeted therapies of BRAF and MEK.  We knew the results would be good because all my palpable (fancy word for things you can feel with your fingers) tumors have gone away so there has definitely been some level of progress.  Now, I have not had any progress against the disease since I was diagnosed over a year ago.  None.  Every month or six-week interval has shown disease progression at varying rates, despite the very aggressive treatments we have tried.  These results from Moffitt would show for the first time that my level of disease has decreased, that I have become more healthy and less sick.  Level of disease can be measured by tumor load, and Moffitt adds the largest dimension of a select group of discrete, easily identifiable tumors.  For me, that's six tumors around my liver, in my lungs and upper torso.  When compared with the imaging study from the end of January, my tumor load has shrunk 61% in ten weeks!  The actual results are higher since the "before" imaging was when I was still on Temodar chemotherapy pills and before the significant cancer growth in February that almost did me in.  At that point, as the Marine saying goes, the enemy has us surrounded - and we have them just where we want them.  Then "boom"!
    Even better news was that my side effects from the targeted therapy have seemed to taper off at the lower dose (100mg instead of 150mg).  Now the side effects are minimal and I'm not at risk of being removed from the study.  And the rigor of my total treatment involves taking three pills in the morning and two in the evening and a day at Moffitt every month.  No wonder this combo therapy has become - as one doctor put it - the "phenom" in melanoma.  A low impact, quick acting, high response therapy for a disease that had almost no therapies with any one of those features.

     There is still the possibility the drugs will stop working at some point of course, but no one knows yet.  The good news is that the targeted therapies are coming on line as fast as the researchers can identify the specific genetic pathways that allow the cancer cells to regenerate.  As well, testing on combinations of targeted therapies with immunological therapies are just being started which promise to both knock-out cancer and keep it from coming back.  Its all very exciting and gives me hope of living a long and natural life, thanks to the miracles of science.  So hug someone in a lab coat today, and tell them thanks for me.
     While awesome news, we are trying to just live in the moment.  We are enjoying not having to deal with this on a daily basis.  I have some breathing room, some time, and I'm going to take full advantage of it.  We've restarted planning a summer vacation, I've committed to some new bike rides for the end of summer as I had to miss the ones I planned on this spring.  I'm setting goals and setting aside excuses.
     After holding the line for a year - my own little Battle of Britain - we've struck a mighty blow to cancer.  We've reduce it to less than half its former strength and the math for the next six weeks looks bad for cancer as well.  I am taking from it its ability to influence my daily life, relegating it to the far off battlefield.  And I have taken from it a renewed appreciation for these blue skies, for now void of black birds and storm clouds.
     Winning.

No Excuses

I was on the treadmill at the office, sweating a little too much and feeling the pain of various aches and pains and dragging from a long sleepless night, and I was feeling great.  I had come to a realization, somewhere about ten minutes into the workout that had - for some reason - escaped me recently.  I had set the machine for forty-five minutes, a normal but not too easy cardio workout before lifting weights and nothing extraordinary.  But once the machine started moving so did my rationalization machine, spewing a torrent of reasons why forty-five minutes was far too much.  I was up all night with a fever and then cold sweats. My legs hurt, and for some reason the bottom of my feet have been hurting the past week.  I need to get back to the office as soon as I can, that project waiting is urgent.  My therapist says I need to take care of myself, rest and take more pain meds and more Xanax to relive anxiety.  And I have cancer for Christ sake, stage IV - and that's really bad.  I should be able to do so much more, anyway, why try so hard to do what seems to be so little. It doesn't really matter. And I deserved a break.  I deserved a pass. I was special.
     That did it, that clicked a trigger in my brain that woke something up inside of me.  The tape loop started playing again, with that weird whirr as the voices and pictures got up to speed. I was suddenly that Marine recruit again at the top of the wall trying to get my leg over the obstacle, face in anguish from impossible pain, drill sergeant screaming in my face all the reasons I was a failure to humanity for not making it over this one obstacle.  I heard the voice of Winston Churchill saying "We do not do this because it easy, we do this because it is hard."  I heard Tyler Durden say "Without pain, without sacrifice, we would have nothing."  I heard that old drill instructor explain "When a Marine quits, he's dead." It's all about this one wall, and it has nothing at all to do with this one wall. This one challenge. This one little workout.
     I could choose not to, I have a fistful of passes that say I do not need to get over this one silly wall.  I'm justified to have those excuses, a lot of important and knowledgable people tell me so.  But that does not change what they are or who I'll become if I use them.  And although mine are pretty good I know others that have better ones but don't use them.  There are people much, much worse off than me who would give a body part to be able to spend forty-five minutes on a treadmill.  Unfortunately, there are those that can only dream of being able to do that before there miserable lives are crushed out like a used cigarette.  There are those that are better than me, that do not even think about plunking down their excuses but get on with life.
     So I took my finger off the down-arrow button on the control screen time setting.  I turned up the speed setting just one notch as punishment for being such a wuss.  I turned the iPod up just a little bit.  I started to focus on the thousands of times I pushed the excuses aside before and got on with it.  The school exams, the job challenges, the military exercises, the bike rides.  This is just another wall to climb, another challenge that will be over before you know it.  And when it is over, that challenge adds just a little something permanent and positive to all that I am.
     And, oh yeah, fuck cancer.

Hold Fast

OK, here's an update since my last treatment (hint, it didn't work).  Thanks to everyone for checking up on me and prompting more posts.  Let's review - so far in this fight against melanoma we've done biochemotherapy (the kitchen sink approach), the adaptive t-cell replacement of my immune system (the behind the lines infiltration), IL2 treatment (carpet bombing) and the Temodar chemotherapy pills (the cold war).  At the end of January I was restaged after four months on the Temodar and, despite some good signs at the end of November, the disease was continuing to progress.  Some new tumors appeared, including one in my skull that was building pressure in head which could lead to some serious consequences (a doctor actually described the situation as "deep do-do").
     Time for a new plan and I was still excited about anti-PD1.  A study opened up at MD Anderson but at a very low dose.  They held a spot for me but I wanted to explore other options.  Moffitt Cancer Center in Tampa had a anti-PD1 study that was pretty advanced.  When I called I found out that they had 1 spot left in the study for an Ippi-naive patient (a patient who never used Ipilimumab) and the anti- PD1 was at a high dose and it seemed like the slot had my name all over it.  So I set up a meeting with Dr. Weber there and filled out the thousands of pages of paperwork and bought a plane ticket.  When I got there they were a little skeptical of my previous treatment choices, but I think it was a lack of understanding as not all the facts are in the clinical notes they reviewed and, again, we are dealing with doctor egos.  But the new medical team was great, and agreed that the anti-PD1 study was a good and viable option.  However, the medical team there also recomended a clinical trial combining the genetic therapy drug BRAF plus the MEK genetic therapy drug.  BRAF is know to have good results in reducing tumor load and has been shown to increase life span by about a year.  After that most people's cancer mutate to a resistant strain that does not respond to BRAF, or any other know treatment.  Because of that most patients do not see their second year, and that's why we kept it in our back pocket as a last option.  In addition, BRAF had some serious side effects with rashes, fevers and additional cutaneous cancers.  However, the combination of BRAF plus MEK did not have these side effects, no one knows why, and may not create the resistance that BRAF alone creates.
     After talking to MD Anderson and some soul searching, we decided on the BRAF+MEK study because we needed to address my not inconsequential tumor load and we're weren't sure we could wait the 4-6 months for an immunological drug like anti-PD1 to take effect.  Plus, its pills twice a day and monthly visits back to Moffitt so a relatively easy regimen given what I've already been through.
     First, we would have to be off of Temodar for 4 weeks before we could start the trial because you generally need to be "clean", which is cancer speak for no cancer treatment and generally no medication for your symptoms in your system that may interfere with the results of the trial drugs.  We figured that this time frame would help us decide one of three things about the Temodar - that:  1) the Temodar was working by holding down the growth of the cancer if we find that, after a month, we have a more aggressive disease progression or 2) that the cancer is progressing slowly on its own regardless of the Temodar if the disease progression over that one month window remains slow or 3) that the Temodar was actually inhibiting my body's (and my new immune system's) ability to fight the cancer and we see a decreasing tumor load after coming off Temodar.
     The third option is the one I held out hope for although the medical team at MD Anderson expressed skepticism.  I figured the second most likely - that Temodar was not doing much at all.  This was not a bad result, if the tumors grew slowly or stopped I could go on with the rest of my life just having the tumors along for the ride but not hurting me in any way.  This was what I was banking on.
     Well, the result was actually behind window number one.  After two weeks I did not feel better being off the chemo, in fact I felt much worse.  By the third week things were getting pretty troubling and my level of pain and general suckiness was growing daily.  In fact, this was the first time I experienced pain from the cancer - up to now all the side effects were from the treatment and not the disease.  And pain is not quite the right word for it, although there was definitely a lot of pain and I had to resort to increasing levels of pain killers to get through the day.  The feeling of the cancer is a kind of hollowness in your bones, like your gut is full of broken glass and you're all busted up inside.  Moving is something best avoided and I had to stop any kind of exercise.  And each day got worse as I tried to hang on without treatment for the remainder of the four weeks.  Every morning brought a new level of pain and tumors started to visibly grow and I even got black eyes from increased pressure in my skull along with headaches and numbness in my extremities.  But pain means you're still alive and I fought through it.  Needless to say, Ann and I got pretty scared.
     As this was happening, the amazing research nurse at Moffitt managed to get all my tests scheduled in order to get me hopefully cleared to start the trial as soon as possible.  On day 29 I was at Moffitt a third time getting my final tests, and then I waited in a nearby hotel for the call that GlaxoSmithKline had accepted me into the study.  There were some sticky points and they did not like the tumor in my eye, we all worried that might make me ineligible for the trial.  However, the next day, February 29th, I got the call and headed over for my meds, taking the first dose at 2:30pm.  Unfortunately, I had a very important business meeting the next two days that I had been planning for over a year that involved flying to the Caribbean overnight and I had to cowboy up for that.  But I didn't get much worse.  By day 4 on the drugs my most obvious tumors had either shrunk or disappeared, especially the cranium lesion which was completely gone.  Ann and I managed to take a weekend to ourselves, although I do not think I was much fun to be with.  The headaches subsided, the pain slowly faded and by day 5 I was off the painkillers and anti-nauseau drugs.  By day 7, my first check-up at Moffitt, I was a new man and I didn't feel cancer sick any more .  By the 10th day I was able to go to Disney with the family and walk through the parks with the kids without wincing.  By day 12 I was back on my bike, and on day 13 I hit the gym again.  Hey, cancer!  Say hello to my little friends BRAF and MEK.  I think this has been a neutron bomb up cancer's ass and an amazing, beautiful thing to watch.  There have been some side-effects, fevers followed by major malaise (a term I used to joke about but no more), but nothing too bad.
     So I should be overjoyed, dancing in the streets and shouting at the moon but it's hard to ignore the dark lining in this cloud.  The anticipated developed resistance to the BRAF drug experienced by others is a definite possibility and can hit me tomorrow or next week and most likely within a year.  No one knows yet if the combination of BRAF and MEK somehow overcomes this resistance.  Medically speaking, there is no reason to expect it to do so but there is also no known medical reason that the combination works so well over the BRAF alone - as I myself have experienced.  We are in uncharted waters, hoping for the best and keeping an eye out for monsters.  Dr. Weber is presenting the results of this study at ASCO this fall, perhaps they will know more then.

     But for now we're victorious, although bloodied, after the challenges of the past month.  Cancer broke through my defenses, breached the wall and made it into the keep.  I fought back and won back my body, that's all that matters.  Live to fight another day, that's all I ask.  But it left an impression and I can still see cancer's tracks in my home.  I have now seen cancer up close, felt its breath in my face, its hands around my neck.  While I can not deny the fear I felt in the encounter, I also feel a stronger resolve.  I feel the adrenaline after getting hit in the face the first time in a fight, the laser sharp focus of survival and the taste of my own blood in my mouth.  I've beaten it down and I can do it again.  For now I'll rebuild my strength, reinforce the fortress and really, really enjoy each and every day.  And we'll keep hoping that the boys and girls in the lab develop some new weapons for me in the next year.  That's no pipe dream, there have been more melanoma developments in the past two years than the past twenty.  Until then - we hold.

Not Dead Yet

OK, it’s been a very long time since my last post so let's get caught up.  I started back at work and started a new treatment protocol – both have admittedly taken a bit of focus off of my cancer fight the past couple months.  Going back to work has been great.  As I’ve mentioned before I really love what I do.  It also gave me back a sense of normalcy, which honestly I do not feel is deserved but I’ll enjoy it nonetheless.  Cancer is not curable; having it is a new normal – at least internally.  From outward appearances, my life has become surprisingly normal even though the fight continues in a less obvious way.  The new protocol is a daily pill, like taking a very expensive vitamin, and even that does not seem cancer like.  Sometimes I wish I was in a hospital bed fighting it out to the end with cancer, but I’ve learned to appreciate low intensity warfare just as well.

 I'm now on daily low-dose chemotherapy drug on a 21 day cycle with 7 days off.  The idea for the protocol comes from a paper published the end of last year from a medical team that tried prescribing Temozolomide to cancer patients who had not responded to high dose IL2 treatments.  Usually such a drug is given to patients who have had a favorable response to IL2, to help continue the response.  Their theory is that the IL2 has amped up the immune system – even if there are no measurable responses – and that the chemotherapy drug attacks the tumors as well as attacking more Treg cells (immune system brakes) than regular T cells (immune system accelerators).  They had response in 6 of 9 patients, and my lead oncologist thinks that the TIL treatment and follow-up IL2 put me in an ideal position to benefit from such a chemotherapy.  I think this is called “novel therapy” because it is not a standard protocol or even a clinical trial (nothing like taking a complete flyer on your treatment).  I just completed two cycles and test results at MD Anderson recently show there have been no new tumors and a slight decrease in the ones I have.  Given that the side effects – general nausea, especially in the morning - and low white and red blood counts, are relatively mild, we are going to continue with the treatment for two more cycles and see if the progress continues.

            If I choose to seek other options, there are many exciting new developments.  Earlier this year the FDA approved two new melanoma drugs (Yervoy and Zelboraf) and there is a new treatment that is getting the community excited called anti PD1.  It works very similar to Yervoy which releases the brakes on the immune system.  CTLA4 is one of those brakes and Yervoy blocks it, PD1 is another brake and blocking that is supposed to have similar effects to Yervoy - but better.  PD1 stands for “program death 1” – not sure how that name came about but I like the sound of it and I can easily picture it chalked on the side of a large air to ground smart bomb.  There are a number of clinical trials under way using a number of drug company’s versions of PD1.  The smart money is usually with the big pharma companies and five of them are racing to put a PD1 therapy in trial (see “Bristol-Myers Squibb Zeroes In On A Blockbuster Cancer Drug”).  There is even a trial combining both Yervoy and PD1, a potentially very potent combination.  Most of the trials are all still phase 1 so they are not something I am willing to ditch my current protocol for, but I’m keeping an eye on the research and planning my next couple moves.

            The past couple months have also been a time for reflection.  After not responding to two different protocols that each were the best shot I had available to me, it’s been very tempting to feel defeated.  While recognizing that statistics are not friendly to me at this juncture (not accepting, but recognizing) the question becomes what to do about it.  Or more pointedly, what to do differently about it?  Take any person off the street and put some parameters around their expectations of longevity and immediately you get a knee-jerk reaction about them suddenly pursuing a bucket list and making major life alterations.  In the business of fighting cancer over the summer I never considered such actions, but in the relative calm of my current protocol it does sometimes float to the surface for consideration.  I do not have a bucket list but maybe I, given the circumstances, should pick up my family and move us all to a beach in Hawaii to enjoy the time I have left?  It is a serious consideration, but in reality no different than before I was diagnosed with cancer or for any of us regardless of health.  And, after a lot of thought, I’ve realized that those flights of fancy would not stand the test of time and that what I truly value in my life is already a reality.  It’s waking up next to my wife and/or dog every morning, it’s watching the girls go to school, it’s enjoying a sunny day on my patio and doing work I enjoy and hanging out with friends.  I don’t want to change any of that, I want it to continue.  This reminds me of what a friend once told me was the definition of wealth.  He said that if, upon coming into a significant sum of money, you would not materially change your life then you are already wealthy.  If someone dropped a huge sum of money in my lap today I would not change the car I drive, nor the house I live in nor my job.  I’d be hard pressed to change a thing.  There’s a lesson in this - for me and, I think, for everyone.

            So I'm in a bit of a weird place, one I did not anticipate in my many projected scenarios of how this cancer battle would play out.  I honestly thought at the end of 2011 that I would be either NED or dead, a middle option never really came up.  And while I cannot ever come to you to report that I am cancer free, nor can I report now that I am NED, I do think I have beaten cancer into submission for now and it feels pretty good.  People can live with cancer indefinately if it is kept from growing so I'm much closer to NED than dead, and its not just that I'm a glass half-full kind of person.  I admit to sometimes having doubts, sometimes being a glass half-empty type, when the labs come back poor or the aches and pains won't go away.  But I learned one very important lesson from that - dying is not any way to live.  We each have in ourselves the power to describe ourselves as living or dying, regardless of our circumstances.  And I'm very much alive, thank you.  I've started reading Not Dead Yet by Phil Southerland who overcame diabetes to accomplish many amazing things in cycling and the fight against the disease.  Inspired, I've signed up for the Tour de Broward and Tour de Cure in March and the MS150 event in April.  Each is a major cycling event that challenged me in previous years when I was in top form.  I have about 16 weeks to get back into shape and overcome the side effects of the chemotherapy if I'm going to complete these events.  I've started riding regularly and systematically, turning my pedals "in anger" as Phil Ligget often says of pro bike racers, but my anger is directed at this horrible disease.  On my bike I feel back in the fight, mano-a-mano with cancer.  Each pedal stroke is a kick to cancer's face, each mile a terrific body blow and each ride another victory round in the squared circle.  Nope, not dead yet.