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.