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.