5 miles...DONE!!!! But, not alone...

It has been over 3 years since I did a five mile run. I worked very hard after all of my surgeries to build back muscle strength and endurance.  Since starting my anti-PD1 trial, almost exactly 3 years ago, I've fought to rally back after every set of injections and infusions.  I walked, I jogged, I did the elliptical, I did INSANITY.  Poorly immediately after the bug juice, then a little better, and a little stronger...only to slide backward again when side effects of aches and pains and tiredness and wheezing would begin again.  There were no 5 milers.  Having had my last infusion in June, I guess Rosie was right when she ran with me in November and said she felt I was getting stronger.  I have gradually increased my weekly miles, running more frequently, running 3 miles more often than the two that was most often what I stuck with over the course of my treatments.  But, today, I decided it was time for 5!  So...I did it.  5 miles in 58 minutes.  No speed record to be sure.  But, no breathers either.  There have been plenty of runs in which I had to stop every quarter, or every half mile, to catch my breath.  Not today.  I am proud.  Proud of my determination to get through all of this.  Proud of working hard to keep my strength to the best of my ability, never knowing what I have yet to face.  But, most of all, I am strong, because of those who run with me.  Those who have helped me, encouraged me, pushed me, rested me and my spirit.  Friends and family who have always filled just the space I needed them to be in...to make me laugh, to hold me up.  So today...my very best ones...propelled me forward again.  Without my Roo, Fred-o, and Bentie...I would certainly never have made it through....much less made my run today.  And while they hold me and I do the same for them...I run for you, too.   It does indeed take a village.  Ubunto - c

Life is just a party, Baby!!!!

We all have so much to celebrate, if we just take a moment to think about it. 

When it is Thanksgiving...and even when it's not....

When we have more than we need to eat...

When we have wonderful peeps and pups to walk with....

Even with graduate application hysteria...

When congratulations are in order...

With a proper British tea...replete with sandwiches and scones...

When there are beautiful friends with whom to share...

When silly laughter rings through the air...

When there is music and dance and love.....

Yep.  In spite of work and worries and septic tank issues and the unknown and melanoma....there is ever so much to be grateful for.  My deepest gratitude to all of you who share my life and bring joy to my little mutant babies!!!  Big hugs and a huge congratulations, Roo!!!  Life it just a party, Baby.  Live it up! - c

Update on PV-10 (Rose Bengal) for melanoma

I first wrote about PV-10 (also known as Rose Bengal, a pretty cheap derivative of fluorescein, that has been used for over 80 years to stain necrotic tissue in the cornea when corneal abrasions are suspected and as an IV diagnostic of liver impairment) being used in melanoma patients in October of 2012.  The study I reported on was one in which Stage 3-4 melanoma patients had up to 4 courses of PV-10 injections into up to 20 cutaneous and subcutaneous tumors.  The cool thing was that not only did many of the injected tumors respond and shrivel, but some tumors at distant sites (even in the lungs) that were NOT injected, shriveled as well!!!

Results:  Objective response was achieved in 51% of target lesions (25% complete response and 26% partial response).  Furthermore, disease control (combined Complete, Partial, and Stable responses) was achieved in 69% of lesions.  In bystander lesions: 33% = objective response and 50% achieved disease control in these lesions.

Yeah, still sucky I know....but in melanoma world....

So...the folks at Moffitt must have thought the original study in mice and this data looked pretty good.  See the report below.....

Single Injection of PV-10 Being Tested in the Treatment of Advanced Melanoma
By:  Jo Cavallo via ASCO post, 8/28/2013

A new study underway at Moffitt Cancer Center in Tampa, Florida, is investigating whether an intralesional injection of PV-10 (a substance derived from Rose Bengal, a staining agent that has been used to assess eye damage), is effective in reducing tumors and the spread of cancer in patients with melanoma.  Early clinical trials show PV-10 can boost immune response in melanoma tumors and in the bloodstream.

"We are in the middle of our first human clinical trial of PV-10 for advanced melanoma patients. In addition to monitoring the response of injected melanoma tumors, we are also measuring the boost in the antitumor immune cells of patients after the injection," said Dr. Sarnaik.

Guess we'll have to see how the ratties do with this one.  Hang in there.  Call Moffitt for more information if this trial is of interest to you! - c

Everything cures/kills melanoma ~ one 'mo one....

If you look back on my post from July 20, 2013 you'll see a large collection of research articles enumerating studies that proved all sorts of things - coffee, cucumin (turmeric), cimetadine (tagamet...med to decrease stomach acid), doxycycline (an older antibiotic), NSAID's (like ibuprofen), and even shitake mushrooms - kill melanoma cells!!!  Well, here's another:  STRAWBERRY JUICE!

Antineoplastic activity of strawberry (Frafaria x ananassa Duch.) crude extracts on B16-F10 melanoma cells
By:  Forni, Braglia, Mulinacci, Urbani, et al.
Of the Department of Biology, University of Rome, via Mol Biosyst, 2013 Nov 4. [Epub]

So....these peeps extracted the juice from strawberries (anthocyanin-rich strawberry fruit crude extracts) and squirted it on some mouse melanoma cells they had scattered about in petri dishes and found.... {DRUMROLL>>>>>}.... "the strawberry extract produced a remarkable reduction of cell proliferation."

Thought you should know.  Now...go have a "fruit snack"!!!!

PS...Fred, Shane, and Rose should never have any worries having eaten more than their weight in fruit a zillion times over!!!  Remember Fred trying to get out of the grocery cart to get to the strawberries when he was a baby, Ruthie????

Wonder if it counts if you eat strawberry ice cream?  Hmmmmm... - c

How am I? Thankful....

Running yesterday, I realized that I had not given an update about ME, in a while....and that's a good thing!  In thinking about how I am, mostly, I am thankful.

I am thankful that even though B doesn't know the difference between violas and pansies....he knows pretty faces are important!

I am thankful, that in our shared, weird and wonderful spirit of celebration and defiance, B and I attended yet another of Vince Gill's annual Song for the Children concerts to benefit the local chapter of the Children's Advocacy Center.  Our first attendance was literally days after my last surgery for melanoma, a tonsillectomy, oddly enough, in November of 2010, just before starting my anti-PD1 trial that December.  Gill and his band provided another amazing show.  Thanks Vince!!!

I am thankful that I got to see another beautiful fall here on the mountain.

I am thankful, that despite about a month's recurrence....that never got as bad as they had been....mouth ulcers and mucositis have been pretty much absent from my world!!!  Occasionally there is a sore spot on my tongue or cheek that worries me...but to be honest...had I not experienced what I have, I would probably not even notice!

I am thankful that I've been allowed to watch B's cherry trees, planted after almost 5 years with melanoma,  grow 5 more years!

I am thankful for a wonderfully delicious and fun Thanksgiving with B and the kiddos.

I am thankful for a job that is certainly keeping me busy, but is filled with many dear patients and friends.

I am thankful, and somewhat astounded that I AM NOT getting scans in the coming week as my heretofore every 3 month regimen required for the past 3 1/2 years!!!!!

I am thankful that I AM NOT going to Tampa in the coming week as I have been for the past 3 years!!!  Will be doing all of those things in March, I suppose...but not this week!!!

I am thankful, despite all its difficulty, that I did have the opportunity to attain the treatment I have received.  Though I do not know how much longer my reprieve from melanoma will be granted, I am certain I would not be here today without it.

I am thankful for the Affordable Care Act.  Through Healthcare.gov, (Yes, the very site that had problems at first, is now working very well!!!)  I have been able to successfully sign up for an insurance plan for me and my children DESPITE my pre-existing condition that is actually CHEAPER and provides BETTER coverage for the three of us, starting January 1st, since Brent has retired and we will no longer be covered by the insurance through his work.  And though I HATE ALL INSURANCE equally and with a passion, it is essential in this day in age in order to have medical care without the risk of financial bankruptcy.  At least this legislation prevents discrimination against the millions of us...including newborn babies, Mr. Hudgens, Mr. Fire and Insurance Commissioner for the state of Georgia....who did NOTHING WRONG...who for all sorts of reasons ended up with that soon-to-be irrelevant label....pre-existing condition!  So, yes, I am thankful.

I am thankful that it seems this blog provides at least some information and succor for those in need.

I am thankful for dear friends and family who keep me in their hearts.

Yes, I am thankful indeed! - c

Way to go, Sally!!!!!

Some of you may remember my excitement at finding a Sea Turtle, named Sally, (Yes, that was her name....she told me!!!) on a Florida beach back in July of 2010.  She came ashore and into my life just as I had advanced to Stage IV melanoma and endured stereotactic radiation for my brain tumor with the removal of my lung's right upper lobe for a tumor within the bronchus.  I could find no additional trial or treatment at that time, but....along came Sally.  If she could survive and complete the tasks her life demanded of her despite mean sharks, gigantic boat motors, BP oil spills, not to mention navigational issues and obnoxious people and their trash, over the 9,000 mile sojourn she had just made...then.... Hey! I could find a way to deal with melanoma!!!

Today, I am happy to share a report from NBC News noting that "Endangered green sea turtles are making a comeback in Florida"!!!!  In 1979, only 62 sea turtle nests were found in the state.  This year: 35,000 were discovered.  Experts credit bans on harvesting turtle eggs, turtle fishing and the sale of sea turtle meat for a lot of the success.  Additionally, the Florida home owners and visitors who have complied with recommendations to turn off lights near beaches, especially from spring to fall during the nesting season, since the lights can confuse hatchlings....drawing them inland toward the lights rather than out to sea...have been very helpful to Sally and her babies as well.  Hazards to the turtles remain in the form of fishing nets and lines, trash (esp plastics and Styrofoam) littering beaches and the sea floor, as well as boats who pose risks to turtles when propellers crack their shells.  But overall, conservationists consider the results "phenomenal"!

Sally and I do, too. - c

T-cells infected with genetically modified HIV...KILL Cancer!

Docs at Children's Hospital of Philadelphia and the University of Pennsylvania are working with genetically modified T-cells to fight leukemia.  T-cells are collected and purposely infected with a virus that genetically changes them in hopes that those T-cells...now dubbed "serial killer cells," will now see and react against the cancer cells once they are reintroduced to the patient.  HIV that has been modified so that it can no longer cause disease, but remains able to reprogram the T-cells, is the virus used in this clinical trial.  The doctors readily admit that this is a last ditch effort, currently utilized only in patients for whom there are no other options, and even with some successes, patients may not survive the procedure. However, you need only see the film below....to hope.

Fire with Fire

Leukemia Patients Remain in Remission More Than Two Years After Receiving Genetically Engineered T Cell Therapy 
University of Pennsylvania Researchser Report on Results of Trial in 12 Patients, Including Two Children   Penn Medicine News, December 9, 2012

In this report they state:  Nine of twelve leukemia patients who received infusions of their own T-cells after the cells had been genetically engineered to attack the patients' tumors responded to the therapy.... Clinical trial participants, all of whom had advanced cancers, included 10 adults...with chronic lymphocytic leukemia...and two children with acute lymphoblastic leukemia.  The report goes on to state that: 2 of the first 3[adults] treated remain healthy and in full remissions more than two years after their treatment.  Information regarding the other patients was not included in this particular report.

Good luck, Emma.  Live free. - c

If money = access to cancer care.....we have a problem!!!!

I have worked very hard all my life.  I've been employed since the summer I turned 13, when I worked five days a week for a local dentist answering the phone, handing him equipment, cleaning spittoons, sterilizing supplies, taking out the trash, and cleaning his home once a week, from toilets to linens to stripping wax and reapplying it to his hardwood floors.  All for $100.00 a week.  And I was THRILLED!!!!  Starting that summer and for all the others, including some school breaks, that followed, until I left that small south Alabama town with my Associate Degree in Nursing, earned at the local Jr. College....Jefferson Davis Junior College...to be exact, I worked for the dentist, earning the same rate of pay, eventually learning to make dentures in his lab, saving my money.  Those earnings allowed me to fund my move to Chattanooga and start work in the big city as an RN in the local Children's Hospital...for $7.70 an hour.  I was in high cotton.  I had an apartment (albeit a tiny one!!!), paid all my own bills, and learned new things everyday.  And, yes, it has been a while back, but this was just in the mid-80's y'all!!!  I've put myself through school via scholarships and my own pay check three times.  Yes, I married a doctor, who put himself through school by working three jobs and taking student loans, which we paid off together during our marriage.  And you know what????  I am lucky and wealthy beyond measure.  Obviously rich in friends and family and life experiences, but those will not buy you cancer care.  The fact that I have been able to afford the care I have attained puts me in a small minority group.  The fact that I could pay for the trips to Tampa and the car and hotel and food it cost me while there makes me different.  I paid the deductibles, co-pays, and the out-of-pocket expenses of $800.00 every three months just for the scans, required for my trial participation, myself.  Moffitt didn't pay for those.  BMS didn't pay for any of those expenses.  How many people do you know who could afford such care?  I don't know very many.  Most of the people I work with, people I care for, my friends and family could not.  Is that right?  I don't think so.  And when you look at the video describing the imbalance of wealth below....sadly the outlook is even more bleak....

Wealth Inequality in America

So, Weber and Ribas agree (see 11/18/13 post) that if you have melanoma (or perhaps more specifically...if THEY had melanoma) you should get yourself to a top-notch melanoma cancer center.  I agree.  I did that.  But, how are most folks supposed to make that happen?  Yes, there are a number of agencies and programs that can provide at least some assistance, but that means that a sick and frightened person is going to have to have the where-with-all to find and access that.

We were all so happy that ipi was approved by the FDA.  Only to find that Weber and Ribas admit, folks are not prescribing it in their local offices or county facilities.  They haven't bothered to credential folks to do it and are not utilizing it because of cost.  They are not willing to eat the wholesale cost of $120,000 if the insurance company won't cover it or if the patients themselves fail to pay for "their portion."  Not really how we all thought this was going to roll, is it?

I don't have a ready answer. I don't know what I am going to do. Do we need a Phase IV trial for drugs AFTER they are approved to determine whether any patient can afford them???  Being diagnosed with melanoma or any other expensive and deadly disease is unfair enough.  Patients carrying that burden should not be denied access to life saving and extending drugs just because of their bank accounts. Should they? - c

Running...thoughts. Alive? Dead?

Running today I found that I was thankful.  Thankful to be running well and easy after having a cold that flared up my asthma for the past couple of weeks.  Thankful that my sweet love was also my very best friend.  That my children are people I admire.  That my daughter and I could agree to disagree about Mrs. Dalloway, "Mrs. Dalloway said she would buy the flowers herself." That she would happily entertain my notions and have such conversations with me.  That I have the very BEST PEN PAL EVER (thanks Jonathan!).  And then....as I ran on, my thoughts turned to menus.  Tuna and soba noodles with sesame seeds, green onion and zucchini tonight.  Pork loin, dressing, green bean casserole, maybe brussies for Bentie, and gooey chocolate cake with rum soaked cherries on the side for Thanksgiving.  A blackberry syrup I need to make for the morning after's bread pudding.  Oh...and I need pumpkin for the pies.  Then, planning the sandwiches and scones with berries and cream for a perfectly British high tea in early December for a very special grad to be!!!!

But, last week, while jogging in a similarly foggy, misty, moisty late fall day here on the mountain, I was contemplating the silhouettes of the mostly bare trees.  A few were still hanging on to their brown and crumpled leaves, but most raised empty branches skyward.  With mild curiosity, I looked over at a neighbor's yard to see if the long dead tree he seems to be taking bets on as to whether it will land on his garage or the power line was still standing.  Yep.  Still there.  But now....it looked no different from its mates.  If you hadn't watched its demise over the past seasons, you would have to look very carefully to see that it is not as viable as its fellow forest friends.  And that made me think.  Do I live like I'm alive?  Or dead?  What do my choices and actions show?  Cause, spoiler alert!!!!  We will all join my now hidden friend sooner than we can imagine.  I won't have a choice about that.  But, I do have a choice about today.  When my leaves are intact, and even when they aren't....am I making the most of being alive?  I've watched some choose to live their life as though dead already, allowing opportunities for joy and love and friendship to wither and dry on their branches.  I don't want to "live" like that.  I don't want to be part of the walking dead, hiding among the living.  I know that everyday may not be filled with joy and delirious happiness...but I certainly want it to be filled with life!!!  Even if slightly random, bizarrely beautiful, and chaotic!  To yours - c

Mo' Money....Mo' Bettah....Melanoma's Therapies (B-RAF, MEK, ipi, anti-PD1) and Their Cost and Availability

 Melanoma:  From Impossible to Treat to Poster Child for Targeted Therapies

AJMC.com  Published online:  October 23, 2013. Produced by Nicole Beagin.  In September, Mark Fendrick, MD, co-editor-in-chief of The American Journal Of Managed Care, led a discussion of experts about advances in the treatment of metastatic melanoma, which examined both the promise offered by new therapies and the issues surrounding cost, payment, and delivery.

Jeffrey Weber, MD, PhD, Moffitt Cancer Center, Tampa, Florida
Antonio Ribas, MD, PhD, Johnson Comprehensive Cancer Center, Los Angeles, CA
Jennifer Malin, MD, PhD, Manager and medical director of Oncology, Well-Point


(Quoted, but edited, by me!)

Weber:  Melanoma has gone from being regarded by many oncologists as an impossible to treat and hopeless malignancy to a disease...that is the poster child for new targeted and immunologic therapies...  That being said, there are major unmet needs in our field because...we still have a pretty narrow repertoire of drugs...[with] pretty serious toxicities, and we are a long way from curing a significant proportion of our patients.

Ribas:  Having seen this remarkable change in a short period of time...is a remarkable benefit to patients...but we are still faced...with many patients who are either not responding, responding for a short time and progressing, or having side effects.

Patients who were treated 2-5 years ago [with immunotherapies]...continue to respond and patients with T24 blocking antibodies, the longest...for 12 years...but we need to make it more efficient for everyone... The B-RAF inhibitors, vemurafenib...then the B-RAF that is called dabrafenib, which is a very recent approval. ....when we select patients with the B-RAF mutation, which is around 50% of melanomas, we are close to guaranteed to have some...patient benefit.

Over 80% of patients have some shrinkage of disease....but the majority - not all of them, but the majority - will progress...and the median duration of response is around 6-7 months, although there are some patients from the Phase 1 trial of vemurafenib who are now going beyond 4 years and are continuing to respond, but that is the minority.

These are targeted therapies that block the driver oncogene which leads to cell cycle arrest and response in the majority of patients... Around two-thirds of the progression mechanisms go through reactivation of the same pathway and a signal through an immediate downstream, a factor which is called MEK, which is a kinase under B-RAF... Then we have the MEK inhibitor trametinib that has been approved to use as a single agent in B-RAF mutant melanoma. But that is not where we are going to be using it because by itself, trametinib is less effective...and more toxic, so it is probably one of the only approvals by the FDA that we know from the start that we are not going to be using in the way the current label is written.  You can use it in combination with the B-RAF inhibitor and you can use it in patients who progress on the B-RAF inhibitor because there is actually no activity there. But there is a lot of activity when you put it together, ...it is one of the examples that I...know in medicine where you have 2 effective drugs, that you put them together and they are not only more effective but they are less toxic...which should impact on the cost-benefit ratio because even though...2 drugs are more expensive than 1, the side effects are decreased and the benefits of the drugs is markedly improved...  I think most of us would agree that this will be a drug that is cost-effective.

Weber:  I think everyone agrees...the expectation certainly is that the Phase II study results...with those 2 drugs are going to show serious benefit and major prolongation of survival, but again we don't have the data and they won't be out probably for another year...

Dabrafenib, trametinib, vemurafenib, and a lot of these drugs are...oral, you take them once or twice a day.  Whereas, virtually all of the immunologic agents that are in development are given intravenously.  Ipilimumab, for example is given every 3 weeks and to be honest, ...we haven't settled on the optimal dose.  There is a big trial of the standard approved dose of the 3mg/kg vs 10. Ten may be better...what implications [might this have] for the cost, because it is not a cheap drug?  If it turns out that the FDA will now approve 10 instead of 3 are they going to triple the price? 

I should add...that the excitement at ASCO...was because there was a combination trial of one of the PD-1 drugs, nivolumab, with the CTLA-4 blocking drug, ipilimumab...where you see in a graph the bars up or down indicating shrinkage or growth, it looked like it was a targeted drug, it was so good.  Toxicity, on the other hand, was not so trivial...Now, not only are we thinking about how do you combine the targeted drug, now you think about how to combine the immunologic drugs, so that is 5 more years of work at least, to work that out, and that will be impressive.

...The key question....is, what is the best sequence of a targeted drug and an immunologic drug?...and it is not just a (single) drug.  It is what combination of targeted drugs and what combination of immunologic drugs, what should be the proper sequence? ...  That is a major unanswered question...

Fendrick:  What can you say about a standard of care, or a lack thereof, in metastatic melanoma...?

Weber:  ...There are the NCCN guidelines...

Malin:  ...before this call, I checked how...NCCN was recommending use of the 2 new B-RAF inhibitors...FDA approved in May, and NCCN hasn't updated its guideline...there is a little bit of lag...

Weber:  I think practices will vastly vary at an academic center like mine where you have 25 melanoma trials.  At UCLA I'm sure it's the same. It is going to be a little different than if you are in Albuquerque, New Mexico, at a good private practice with 5 other oncologists.  It is going to be very, very different as to what you can offer the patient.

Malin:  This brings up the issue of access.  These therapies are very exciting and the benefits that some patients have are really tremendous.  It is exciting to see someone go into a complete remission following 4 treatments with ipilimumab and stay in remission...for a year...  But, the wholesale cost of just the drug...is $120,000... Most small, independent practices (are) concerned about...taking on the financial risk of a drug that is that expensive without knowing whether the patient's insurance is going to cover it, whether the patient can afford whatever their copay might be.  If they have a 10% copay, that is $12,000 right there, so the cost of these drugs, at least in combining them, is going to bring new questions regarding access for people...

People can have long remissions...and some...benefit from retreatments...Does it mean someone is going to need to repeat treatment every couple of years?  ....When someone gets treated in the outpatient setting, usually the cost is double or triple, so just for ipilimumab, we are looking at a cost to the patient's payer....of $240,000 - $360,000...

Weber:  I think this is something that is at the top of everybody's consciousness...just about every professional group is going to emphasize the idea of trying to have biomarkers to select the right patients.  You can't just treat 100 patients and benefit  8 of them.  It is not going to happen in the future, the FDA has made it very clear how important they think biomarkers are.  ...  I predict that you are not going to get the (Oncologic Drugs Advisory Committee) and the FDA to approve drugs or push forward unless there is clear significant value; a 5 week prolongation of survival is not going to cut it in the next 10-20 years, not when the drug costs $120,000 for the wholesale price....

I suspect if you graph the price of current drugs over the last 20 years, you would see at least a linear increase with a doubling every 5 years and eventually what is it going to be, $300, $400, $500 or $600,000 to treat someone?  That is not practical....I'm not an economist, but I find it hard to believe that for [drug companies] to stay in business they need to charge $200,000 a year for dabrafenib and trametinib.

Ribas:  ...In places like the county hospital, it is hard to find any patient who has been on ipilimumab because it has not been approved for administration even though it is an FDA-approved drug and there are randomized trials that demonstrated approval and survival.  Those randomized trials showed improvement that is based on a small percentage of patients, around 10-15%...  We don't have a marker and possibly we will not have a marker, because it is an agent that is activating the immune system very far away from the tumor, so there are several thousand genes that are involved... It is unrealistic to think that there is going to be one biomarker that says this works or doesn't work in patients... We have dedicated over 5 years of research...and we are back to where we were...we give it to everyone because we don't want to miss those patients that can go on to have decades worth of life...free of metastatic melanoma. That is something I have trouble putting a price on, but the worst case is when we don't even have the chance to give it, and that is what is happening with the price of ipilimumab being so high....it is not only the wholesale price, it is the total bill that I see, and I am outraged every time a patient comes and says, this is what your clinic charged my insurance to give 4 doses of ipi.

Weber:  We have...the occasional referral...a charity patient who has either Medicaid from another part of the state, like someone from Miami, and the University of Miami will not treat them....and Moffitt will eat the cost of some percentage [for] those patients, or BMS will make the drug essentially free... A lot of companies have these programs where if you can't get anybody to pay for it, they will give you the drug for free...so eventually it happens, but it can be a huge hassle...

Ribas:  There are patients who don't get to our clinics.....when I talk to doctors [in county hospitals], they tell me that it is very seldom [they] are able to give ipi to a patient because of the cost.

Weber:  I can see that being an issue for the poorest patients....this was a huge topic...at [an] Advisory Board I recently attended at ASCO....the question was, what if the price were $300,000 or $400,000 to get treated with some regimen lasting a year, would that be realistic? 

Fendrick:  ...I want to ask one thing that comes up a lot...what [do you think] about the idea of a situation where patients would get better coverage...if they went to Centers of Excellence for specific types of cancers?  Do you think it would be a good idea or a bad idea for particularly rare cancers to follow a model that we've had in place for transplants for decades?

Weber:  ...I wouldn't have a problem with seeing more patients and bring more business to places that excel at what they do.  To be honest, if I had metastatic melanoma...I would probably go to the big center, no question...

Ribas:  I would agree.  Sometimes we see patients on a second opinion, coming from the community. The data the community doctor has are the same as we have, the drugs are the same, but the usage may be wrong because they are not thinking about melanoma every day.  My thinking is that regardless of the cost, if we treat, it is cheaper than if we don't treat.  I mean treat...a medical condition and the medical condition improves...

...With all of this discussion I wanted to bring up one thing...I know is going to change even further...the PD-1 and PDL-1 antibodies are going to change...the treatment of melanoma again within the next 2 years...   If we look at the data right now, [it] suggests that we will get a significant fraction of patients with metastatic melanoma to have durable responses with therapies that are basically non-toxic or [with] serious side effects that need [intervention] and will leave the patient in the hospital....There are 7 of those PD-1, PDL-1 antibodies in the clinic [under] development right now....  3 of them...positioned to have licensing potential in melanoma and maybe many other cancers.

Malin:  ...Clearly the cost of these new drugs is a challenge...in just a few years...the cost will be half of the median family income.  So, clearly, it is not conceivable that costs can continue to go up...  The good news is we think that 30% of what we spend on health care is waste, so if we can figure out how to stop doing the things that don't help people, we can insure that we can continue to make sure to make new therapies that are highly innovative available to people, but figuring out where that waste is, and getting people to stop doing things that don't provide value is challenging...

...You look at the fact that there are 3 aromatase inhibitors that have gone generic, in 2 of them the price dropped to $20 per month [yet] one of them is still $300 per month, but most oncologists don't even realize there is a difference in price, that either the patient...or the employer is paying...a difference in cost for a very active therapy that is equally effective...

Fendrick:  ...on the issue of clinical nuance, [it] is critically important to...identify...services that differ in the value that they create and the current benefit designs that patients see.  They pay the same out of pocket for lifesaving drugs as they do for drugs that I wouldn't give my dog... [We need to make] those services on which the evidence is strong accessible to patients and profitable to providers, and hopefully turn the corner and no longer make it profitable or easily accessible to patients,...services for which the evidence is weak, or in some cases, where there is true evidence of harm.

Audio link to discussion between Weber, Ribas, and Malin

Money, money, money!  My current working theme, huh?  Makes me tired.   - c

Counting Stars

So many thoughts lately. People once trusted. Their betrayals.  Lies I've believed.  Working so hard to live.  Facing fears.  Facing pain.  And...now....what?  What does one do when you cross all those bridges?  Do you dare...HOPE?  That four letter word?  How do you prove it was worth it?  To the world?  To yourself? But I know, if perversely.... Everything that kills me makes me feel alive!

Counting Stars - One Republic

Lately, I've been, I've been losing sleep,
Dreaming about the things that we could be.
But baby, I've been, I've been praying hard,
Said no more counting dollars
We'll be counting stars, yeah we'll be counting stars.

I see this life like a swinging vine 
Swing my heart across the line.
In my face is flashing signs
Seek it out and ye shall find.
Old, but I'm not that old.
Young, but I'm not that bold.
I don't think the world is sold
I'm just doing what we're told.
I feel something so right
Doing the wrong thing.
I feel something so wrong
Doing the right thing.
I could lie, could lie, could lie...
Everything that kills me makes me feel alive.

I feel the love and I feel it burn
Down this river, every turn.
Hope is a four-letter word.
Make that money, watch it burn.
Old, but I'm not that old.
Young, but I'm not that bold.
I don't think the world is sold
I'm just doing what we're told
I feel something so wrong
Doing the right thing.
I could lie, could lie, could lie...
Everything that drowns me makes me want to fly.

Take that money, watch it burn.
Sink in the river the lessons I learned.
Take that money, watch it burn.
Sink in the river the lessons I learned.

Everything that kills me....makes me feel alive.

Lately, I've been, I've been losing sleep
Dreaming about the things that we could be.
But baby, I've been, I've been praying hard
Said no more counting dollars
We'll be counting stars.

We'll be counting stars.

Everything that tried to drown me...makes me want to fly.
Thanks, One Republic (and Rosie for sharing).  You said it well.
For all of you, come with me. Let's fly.- c

For the love of money....BMS, Roche, and Merck

Money, money, money, money....O'Jays

(Click the link above...and let it roll while you read below!!!)

Money, money, money, MONEY
Some people got to have it
Hey, hey, hey...some people really need it.
Hey, listen to me, y'all do thangs, do thangs, do thangs - bad thangs with it
Well, you wanna do thangs, do thangs, do thangs - good thangs with it - yeah

FierceBiotech:  MK-3475, Merck.  October 8, 2013. By John Carroll
Peak sales potential:  Maybe $500 million for melanoma with the blockbuster money coming if a whole lineup of cancers is added.    The scoop:  Merck needs this one badly... Under growing pressure from Wall Street, which has come to expect nothing but disappointment, delay and failure from Merck over the past few years, the pharma giant is circling its best research wagons around this PD-1 immunotherapy drug.....turning heads at ASCO last summer...barring a big blowup in the clinic, this program has the potential to prove that the company still knows how to do serious drug research effectively.  The stakes are incredibly high, with no room for failure or even temporary delays.

FierceBiotech:  Nivolumab, Bristol-Myers Squibb.  October 8, 2013. By John Carroll
Peak sales potential:  Analysts have pegged peak sales potential at around $6 billion for nivolumab and the breakthrough BMS drug Yervoy.  The scoop:  Two years ago at ASCO the deal makers were circulating the halls in search of new immunotherapy programs to bargain over.  This past summer, the first round of human data started coming in in a big way, and the incredible promise of these therapies to add significantly to survival times, after years of incremental steps, moved drugs like nivolumab directly to center stage in the big cancer meeting in Chicago.  Bristol-Meyers isn't wasting any time in exploring the full potential for this therapy.  It has 6 late stage studies under way for nivolumab, with fast track status in place for melanoma, lung cancer, and kidney cancer.  If the data continue to come in to support these early results, BMS will have a major new therapy to rely on.

FierceBiotech:  MPDL3280A/RG7446, Roche.  October 8, 2013. By John Carroll
Peak sales potential:  As a leader among the top three immunotherapy developers, Roche is widely seen as a top contender for a drug capable of earning $2.5 billion to more than $3 billion a year.  The scoop:  While Merck's MK-3475 and Bristol-Meyers Squibb's nivolumab operate on PD-1, Roche believes it can have the same impact on cancer by hitting the opposite end of the target: PD-L1 .  Roche has an immense amount of cachet in the cancer field.  Its acquisition of Genentech put it in charge of one of the most impressive development outfits in the world.  All leaders in the field are racing ahead, gathering human data in a lunge for early approvals.

All those poor little rich boys, running super rich companies, lurking in the halls of ASCO meetings....all to save the lives of dying, suffering patients.   Right?  I mean, that's what it's all about right?  Not Wall Street.  Not market share.  Not profit margins.  Patients.  Right?  Right?????

For the love of money, People will steal from their mother.
For the love of money, People will rob their own brother.
For the love of money, People can't even walk the streets,
Cause they never know who in the world they're gonna beat
for that mean, oh mean, mean green.

Almighty Dollar!  Cash Money!
For the love of money, Don't let it, don't let money rule ya.
Don't let it, don't let money fool ya. 

"Human data" for big pharma.  Hmmm....  So, that's what I am?  Interesting.  And to think how much I had to pay to be in THEIR trial....to make THEIR numbers look good.  Glad things are looking up for all of them.  Hang in there ratties.  Hang in there.  I always said, long tails come in handy.  - c

  

Ipi, BRAF/MEK, Anti-PD1 [and NO MORE DACARBAZIN???!] - per chat with Antoni Ribas

A conversation in the wake of data presented at the European Cancer Congress 2013....

Ipilimumab Goes the Distance in Melanoma
Antoni Ribas, MD and Caroline Robert MD.  Medscape.com.  October 8, 2013 [excerpts]

Ribas (David Geffen School of Medicine at the University of California Los Angeles):  We have BRAF inhibitors, the BRAF plus MEK combinations, ipilimumab, PD1, and PD-L1 antibodies. We have heard important updates... Let's start with the long-term updates on ipilimumab (ipi).

Robert (Dpt of Dermatology at the Institut Gustave Roussy in France):  We are happy to see that plateau with...ipi.  We would like to have more patients responding, but we are happy to see that when patients survive at 3 years, the odds are that they are still going to survive at 5 years.

Ribas:  [We] have talked many times about this hallmark of immunotherapy - that when you have a good immune response to the cancer, that can be extremely durable.....we are seeing that play out with ipi, which is great information.

How is [the combination] of BRAF and MEK inhibitors improving on what we have with BRAF inhibitors alone?

Robert:  It is the ideal combination...together, [these 2] drugs, have better efficacy with a longer duration of response, and you have fewer adverse events.

Ribas:  ...the data from dabrafenib and trametinib (BRAF and MEK inhibitors) published in the New England Journal of  Medicine, suggesting a higher response rate, a more durable response with fewer skin side effects from blocking a paradoxical MAPK pathway activation.  [In another study], a dose escalating phase 1 trial using vemurafenib, a BRAF inhibitor, with cobimetinib, ..another MEK inhibitor.  By putting them together...the response rate was extremely high.  They reported a 95% objective response rate.  It is close to a near guarantee of having a response at these levels, and we haven't reached the median progression-free survival, telling us that the curve is staying up quite a bit.

As we get more responses, are they lasting longer?  The BRAF-plus-MEK combination is telling us this.

Robert:  Unfortunately, what we hear is that when patients have failed a BRAF inhibitor previously, then not a lot of them respond.  Only about 15% of patients responded.

Ribas:  This study is telling us something...biologically important....we can get a secondary response by adding a MEK inhibitor to patients who are progressing on a BRAF inhibitor.  Whenever there are mechanisms that are dominant in activating MEK...all of theses patients respond.  The problem is that it is not a durable response.  And when we add the MEK inhibitor, we find another mechanism of resistance. So, melanoma is still trying to fool us, but we are also making progress on other fronts, by taking away another checkpoint:  PD-1 and PD-L1.

Robert:  We are amazed at the results that we see with PD-1 blockade....a lot of patients responding: 30-40%. And though we have less follow-up than we have with the drugs that are on the market, we have the feeling that we are seeing long-term responses, and the side effects are not bad.  Now we think that it can be combined with an anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4)  {like ipi} agent for an even higher level of response.

Ribas:  ...follow-up data on the combination of ipi (an anti-CTLA-4 blocking antibody) and Nivolumab (a PD-1 antibody)...[shows] a very high rate of objective responses, more than 50% in the dosing regimen that is taken forward, with most responses continuing on.

Robert:  This is also why we might now have to change our endpoint....when we know that we have drugs that are so effective, to wait until overall survival is confirmed at the end of a phase 3 study.  What do you think about using progression-free survival as an endpoint for our patients?

Ribas:  Flaherty (from Mass General) presented... a study in which they looked at...data from patients who were in randomized trials that had dacarbazine as the control arm.  We are not even using this word anymore in conversations about melanoma because so many agents have improved overall survival....and taking all the studies...comparing ipi and dacarbazine vs dacarbazine, ...vemurafenib vs dacarbazine, dabrafenib vs dacarbazine, and trametinib vs dacarbazine - all of these studies have shown that another treatment was better than our old standard.  For you and me it is difficult to sit in front of a patient and talk about the control group to which (for the purpose of the phase 3 study) we cannot give a highly active agent that is already out there.  Knowing that progression-free survival may be a hard endpoint that correlates with overall survival would be a great thing.

Amen!  Stop using crap as a control arm.  Patients deserve better.  As a last ditch effort, when all else has been tried....sure....if the patient wants to throw some dacarbazine at melanoma...by all means.  But, stop wasting rattie time, energy, dollars and lives in testing new and better drugs against old meds we know they beat already.  To continue to do so does not produce effective trials....only pseudo science.  And benefits whom?  Drug companies?  It certainly doesn't help anyone else!

Hang in there ratties!!! - c

Melanoma patients...alive and kicking 10 years after ipi!

Only in melanoma (and a few other horrifying diseases) is ten years post treatment an amazing wonder and something to cheer about!  Oh, well.  We'll take it!

Some Melanoma Patients Living for up to 10 years After Ipilimumab
By: Zosia Chustecka. Medscape.com. September 28, 2013 [excerpts]

The dramatic impact that the immunomodulator ipilimumab [ipi] (Yervoy, BMS) made on the treatment of advanced melanoma is shown in new long term data reported at the European Cancer Congress 2013.

Dr. Hodi presented long-term data from a pooled analysis of 4846 patients, which showed a plateau in the overall survival - with 21-22% of patients alive at 3 years, 17% still alive after 7 years, and no deaths after that.  "The longest follow-up in the database is 9.9 years," he said.

"This is a huge paradigm shift in the treatment of melanoma from where we were just a few years ago," he said.  "What it means for us as clinicians is that we can start talking to our patients about the possibility of turning melanoma into a chronic disease, which we couldn't even imagine a few years ago."

Ipi, approved in 2011, in Europe and the US, has a novel mechanism of action, interfering with the immune system instead of acting directly on the cancer. It targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a protein found on the surface of T cells that acts like a brake; the drug removes the brake, allowing the T cell to go into attack mode and kill cancer cells.  This product is typically given as a course of 4 injections during a period of 3 months, and some patients receive retreatment and/or maintenance therapy.

For some patients it seems that this short treatment is enough to reset the immune system and reach a new balance...in which "tumor cells are still present, but are being kept in check by the immune system," Dr. Hodi explained.

He noted that response rate to ipi is low, only about 10-15%, but in some patients, a few doses of this drug result in long-term survival: "more than 3-10 years' survival in 17-25% of patients."  He predicted that these survival results will be improved further with the anti-PD1/PDL1 monoclonal antibodies that are in development.

The long term data come from a retrospective pooled analysis of patient data collected from clinical trials as well as expanded access programs in which patients were treated before [ipi] was approved.  [It included previously treated and untreated patients, getting 3 or 10mg/kg doses, given every 3 weeks for 4 doses, and with or without, retreatment or maintenance therapy.]

None of these variables appeared to have had an impact on survival.  "The plateau, which started at 3 years and continued through to 10 years, was observed regardless of dose (3 or 10mg/kg), whether the patients had received previous treatment or not, and whether or not they had been kept on a maintenance dose of the drug," Dr. Hodi said....he emphasized that this was not a randomized comparison, so direct conclusions cannot be drawn.  "However, these results are consistent with our findings from randomized trials and confirm the durability of the plateau in overall survival, previously shown to extend to 5 years but now shown to extend up to 10 years."

Just think, ipi was not even on the market when I started this Stage IV journey.  May even greater improvements that facilitate a lasting response in a much larger percentage of patients be available SOON!!!! - c

Melanoma Avengers....Cool Running!!

Check out the links:

Running Rosie


13 miles later...


Fast Freddie at the Finish!!!

My most amazing avengers, running buddies, best pals, and the most wonderful kids...EVER!!!!
Much love - mommy

Happy Halloween

Making Punkins!!

A ghoulish process!

The Man with The Tools!!!

Every year, Bentie...making punkins...for 23 years!!!

Now that's not so scary!

Trick or Treat!!!

Halloween....What does the fox say??????
Check it out!  Cause I can't help myself!!!  Happy Halloween!!! - c

The Melanoma Avengers!!!!!

Yep!!!  The weekend came for our 1/2 Marathon relay in Kingsport!!!

 

The Melanoma Avengers!!  Chill'n the evening before the race!

 

 

RACE DAY!!!  Iron Man, Thor, The Hulk and The Black Widow!  Melanoma doesn't stand a chance!!

My boys!!!

Cool Iron Man!  Sexy Black Widow!

Can Iron Man handle all this???

Uh oh!!!!  He may crack under the pressure!!!

Want to know my secret?  I'm ALWAYS angry!!!!

The best HULK ever!!!

The best Melanoma Avengers a girl could ever have!!!!

If the pictures fail to erase all doubt....we had the best time together this past weekend!  The kids were awesome!  Rose kicked the first 4 miles LIKE A BEAST running 7:30 mile pace.  Bentie brought it to me like a champ with Rose keeping pace beside him.  I grabbed the slap bracelet and took off with Roo for the next three.  (That girl is amazing!!!)  Running my best in what had suddenly turned into a cloudy, chilly day!  With Rosie right alongside, keeping me cheered and focused with her chatter as though she hadn't already run 7 miles!!!   And then....Freddo took over....BRINGING IT with 6 and 7 minute miles!!  We came in as a team at 2 hours 2 minutes, while Rosie did the whole she-bang on her own in 2h 8min!!!  We placed 46th of 125 teams!  Hey!  I'll take that!!!  But, best of all.....
WE WON!!!!!  We were all there.  Together.  Strong.  Happy.  Alive.  With love.  NOW! 
Take that...melanoma!!!! - c 

Make new friends, but keep the old....

Friends, old and new, have been so...
You know?  Words can't even describe the support and love that all of you have so generously given.  I don't know how I would have made it through these past years without my besties!!!  All my Peds Care peeps have been amazing!  Dan and Don! Les and Kay! Keith and Janara! What would I have done without all of you?!!!  There are new peeps...now dear.  Jonathan, Jeanne, Steven. Through it all, some old ones have followed and supported me onward.  Terri, my sweet friend/twin, you have no idea how much knowing you were there, behind it all, has meant to me.  And over the past years and days....other oldies have surprised me, by their remembering, and reading, with support and kind thoughts.  Thanks to you all...David (gotta learn how that 'Jo' got in there!!!), Terrie, Scott, Lisa.
Make new friends, but keep the old...
Love to you all....old and new - c

Side Effects of Nivolumab....final thoughts....

Cumulative - Increasing by successive additions. Increasing with severity with repetition of the offense.

I found reviewing my blog posts relative to the side effects I experienced enlightening.  Symptoms started earlier than I remembered.  Wheezing every 1-2 weeks after a treatment was far more obvious and consistent than I had realized.  I ended up missing three days of work all told, due to such symptoms over the 2 1/2 years of treatment. While not noted on my blog, many of my arthralgias included not just pain in the joint affected, but redness and some swelling as well....much like that experienced by a patient with rheumatoid arthritis. The mouth issues have been a recurring nightmare and clearly cumulative...ie increasing in quantity and duration as I progressed through the trial...as has my vitiligo. Therefore, I have a bit of a bone to pick with docs who continue to tell their patients that the side effects from this drug are NOT cumulative.  Nobody got colitis, pneumonitis, or thyroid failure with one dose.  It was something they developed over time.  So....while it is hard to know exactly what we can and cannot attribute to anti-PD1, I feel that many side effects are consistent over multiple patients and do, in fact, increase with increased dosing.

As far as evaluating pain and fatigue is concerned...I have long wanted to develop a "pain-o-meter"!  It would be ever so helpful to have when evaluating patients or reporting how you really feel as the patient!!!!  Was my fatigue and aches and pains less than many of the other patients in the study?  Maybe so.  Or....maybe I'm just really stubborn.  Who knows?  Hang in there, my ratties!  Hang in there!

Finally, it is very strange to feel (sort-of) like I am looking at all this from the other side.  I've been thinking a lot about that lately.  It seems a very odd and unlikely place to be.

For my fellow ratties!  You can do this!  I KNOW you CAN!!!! - c

Side Effects of Nivolumab....my story....

While this is my story of MY side effects, the way drugs affect different people will vary greatly.  My regimen was to be given an IV infusion of anti-PD1 (Nivolumab, formerly BMS 936558, and before that - MDX1106) at 1mg/kg dosage, every 2 weeks for six months, then every three months for 2 more years.  Additionally, since I was simultaneously given 6 intramuscular injections of peptide vaccines every 2 weeks WITH the anti-PD1 infusion for the first 6 months...my side effects related to granulomas, with pain and redness in my thighs, and the development of inguinal nodes, will not apply to those of you getting anti-PD1 alone.  Which is good!!!  Research in my study and others determined that the vaccines didn't help a bit and are no longer used in trials at Moffitt.  I thought of different ways to present this data...but decided that my own words from prior blog posts at the time they were occurring was best.  My infusions (apart from the first one) always took place on a Friday.  My normal work schedule has been 12-hour shifts on Mon, Tue, and Wed. Here goes:

Dose 1 = 12/27/2010
   Sites of the local injections to my thighs were red and tender.
Dose 2 = 1/14/2011
   Thigh at injection site = sore and bruised. Already getting "contra-lateral" reaction...meaning the leg that was injected LAST time...became red and tender as well, within 2-3 days after infusion/injections.
Dose 3 = 1/28/2011
   Twenty-four hours after my third dose I felt beat up and sore all over "like [I had had] a big work out the day prior" but had not!
Dose 4 = 2/11/2011
   Two days after this dose, I noted the development of vitiligo on my hands and arms.  Ten days later: "really tired".  Brent pointed out that at this point the half lives of the medication had converged and therefore remained at a steady state somewhere following the 3-4th dose.  This was later confirmed by Dr. Weber.
Dose 5 = 2/25/2011
  On Sunday, after Friday's infusion, "I feel like something the cat dragged in...after Zeno played with it for an hour!"  That's not good y'all!!!  I took my first Monday off from work.
Dose 6 = 3/11/2011...3 MONTHS DONE!!!!
   At my visit, Weber reports that fatigue is the most common side effect being reported in my study.  Since I was still working and running, he assigned my fatigue, as I reported it above, to be a "1" on a 1-4 scale with 4 being the highest.  He was pleased to note the enlarging lymph nodes in my groin.  Pain in legs at injection sites continues.
Dose 7 = 3/25/2011
   My scans at the 3 Month evaluation showed "ground glass appearance" in the right lower lobe of my lung.  I was also having wheezing at the time.  Scans were reviewed by the tumor board at Moffitt and determined to be related to my asthma or an inflammatory process that Weber had seen before in patients on ipi.  Wheezing gradually improved on albuterol and inhaled corticosteroid; symbicort. Perhaps most importantly, the 3mm something???? in my brain on my MRI when I started is GONE!
Dose 8 = 4/8/2011
   Was told a patient in my study had developed retinitis.  Vitiligo increasing.  Hemoglobin decreased, possibly due to leukophoresis.  Sore, itching legs.  I smell and taste bad....at least to me.  Others report no notice of smell.  I have developed mouth ulcers.  For the past couple of rounds my mouth had felt "dry and weird" immediately following my infusion, for which Ruthie would get me a lemonade, that helped.
Dose 9 = 4/22/2011
   Weber reports that rash, itching and fatigue are being commonly reported at my visit. His conclusion:  I am less tired than most.  Patient in 3mg/kg cohort had to be removed from study due to partial blindness following inflammation of the optic nerve, but was improving with steroids and discontinuation of meds.  When I reported mouth ulcers that had decreased for the moment, Weber noted that I am the second person to develop mucositis.
Dose 10 = 5/6/2011
   Mouth ulcers are present by the afternoon of treatment, along with significant joint aches and rash....red papular and itchy to back and legs.  But, 2 weeks later mouth lesions have faded.
Dose 11 = 5/20/2011
   More of the same.
Dose 12 = 6/3/2011....6 MONTHS DONE!!!!....last every 2 week infusion!
   Vitiligo increased, now to arms, back and chest.  Very itchy....sometimes with visible rash, sometimes not.  By August, itching continues and I think that maybe it gets worse in areas just before they develop vitiligo.  Hard to tell.
Dose 13 = 9/13/2011
   First dose of anti-PD1 with NO VACCINES!!!  Administration seemed like a breeze.  Weber took pics of my vitiligo this time.  Tried to explain various skin lesions to Weber.  Sometimes it is more like a "rash" with scattered red papules. At other times, there are "papular, rough nodules that grow in size, scab over and then gradually resolve though this can take weeks.  He felt they were due to inflammation and its resolution as cells were destroyed."  Had "persimmon mouth by noon".  Within 24 hours, arms and legs "felt as though they weighed a zillion pounds a piece" with aches in ankles and knees. I posted my first pics of my vitiligo on my blog that month.
   The strangest lesion I developed during this entire 2 1/2 year period occurred in November 2011.  Brent remains convinced that had the lesion described below been biopsied, it would have been melanoma.....

Sunday, November 6, 2011

Anti-PD1 and crazy skin thing 9 zillion and 1....

Ever since my last infusion of anti-PD1 in September my skin has been flared up and irritable.  The granulomas on my thighs have remained red, hard, inflamed and itchy. Back and arms very itchy.  Bilateral inguinal nodes have remained constant (they used to come and go) with the one on the right measuring about 2cm and the largest on the left measuring about 1.5cm, followed with another of about 0.5cm, and a tiny one finishing out the trio. Vitiligo continues to increase. Just before our trip to California (10/4 or 5), during a very itchy flare on my back, I noticed a small circular patch of dry skin just below the scar from my initial lesion.  I completely forgot about it during our vacation.  But, when we returned (10/15), I was very surprised to feel a lump there. The documentation follows: 
10/15 - 8.1 X 5.5mm smooth, flesh colored, circular, domed lesion in the exact same location as the dry patch below my original excision scar.
10/17 - size unchanged, texture the same, color now = dark pink.
10/20 - lesion remains same color, size now 7 X 5.5mm.
10/21 - lesion now 5 X 5.5mm with a black scab covering 15% of the top edge.
10/22 - more of a scab has developed, size = 5X4mm.
10/23 - 5 X 3.5mm, with surface now dull and a greater area is covered with a scab.
10/25 - 5 X 2.5mm, lesion now mostly flat scab
10/26 - scab missing, flat pink macule is all that remains.
Today - Brent can find nothing more than a flat, ovoid, pink area.
So...what was all that business????  Brent was very worried.  At first he wanted me straight to derm to have it removed and analyzed.  Then, worried about being kicked off my trial, we decided to watch and wait.  Was it one of the lesions that Weber, Ruthie, Brent and the NP already observed...some inflammatory nodule often occurring before more vitiligo?  Was it a met...which I think is what Brent feels it was?  Melanoma mets can be black, or bluish, or pink, or red. I don't know.  It was truly weird and unlike the other lesions was very smooth, at least initially.  The others have been almost like a pimple or a bug bite for the first couple of days, rapidly turning brown and rough...but never with a black scab. Brent worries for this posting. But, perhaps, one day, such documentation will make a difference.  Anti-PD1 is new...and nobody is talking. Given how challenging the last infusion was, I can't say that I'm looking forward to my next trip to Tampa on Dec. 8th for infusion on the 9th...given, of course, that scans are clear on Dec 2. Then again...maybe it's still fighting off cooties and is the only reason I'm still here!

Dose 14 = 12/9/2011...1 YEAR DONE!!!!
   "I know it is time for my bug juice since I feel fully energized, though nightly itching, occasional weird rashes, ever increasing vitiligo, and the sensation that my tongue has been run over by a road grader...continues."  We were told at this visit that "3-4 of 50" patients in my study have developed vitiligo.  Even at that time, Weber spoke of his desire for a "sandwich study" with patients getting a couple of months of anti-PD1 followed by ipi then finished with some prescribed quantity of anti-PD1.
   I was very itchy for weeks after this infusion with a rash to the torso and flares of prior vaccine injection sites (granulomas becoming red, hot, swollen....again!) even though it has been 6 months since any vaccines were given.  It is becoming clear that I always have an "asthma flare" about 1-2 weeks after each infusion!  Hmmmmm.....
Dose 15 = 3/2/2012
   At this visit I learn that there have been 2 patients in my study to develop colitis...with one currently hospitalized...and two episodes of patients with pneumonitis.  It remains unclear whether patients on the 3 or 10mg/kg are having increased side effects since they are still so early in their trial.  For the first time, 20 minutes into the infusion of anti-PD1, I developed a small itchy and specific, obvious blotch (hive/urticaria) to my right cheek that faded within 30 minutes or so after the infusion.  I later learned they are premedicating groups at a higher dosing level with Benadryl and Zantac.  Within days of the infusion there are significant arthralgias in my ankles, knees, elbows, and wrists.  My mouth feels dry and "weird" but no lesions so far.  Feel "stinky" and smell and taste myself!!!  And, that's not good!
   One week later....mouth lesions are full blown.  There are red flared granulomas to prior injection sites and continued increased size to bilateral inguinal nodes.  Arthralgias continue off and on.
   By April first, mouth lesions are gone and aches and pains are much improved.
   April 14:  Awakened from sleep at 2AM tongue hurting, joints throbbing.  Spent the next couple of days feeling as though I had just been given the med, but gradually improved.
Dose 16 = 6/8/2012...1 1/2 YEARS DONE!!!!
    Side effects were not too bad this time.  There was sensitivity and tenderness to my tongue, but no lesions.  Pain in hands, wrists, and elbows....at first enough to waken from sleep....but then just dull and achy.
Dose 17 = 9/7/2012
   Had another episode of hives to my face during the infusion.  Very tired after.  Worked the Monday following with all my peeps saying..."You look tired!"  "You're pale.  Are you okay?"  Had muscle aches like you might feel with a high fever....but....NO fever!  On Tuesday, sore muscles were better but had pains in wrists and ankles.  Two weeks later - all side effects were better, though aches to shoulders and wrists continued.
Dose 18 = 12/14/2012...2 YEARS DONE!!!! 
   On 12/16 I wrote:  "Itchy, Stinky, Achy, and Tired...the Four Horsemen of anti-PD1!!  Just finished an INSANITY workout...Yeah, yeah...it was only the cardio recovery set...and yes, I did feel like I was going to throw up once...but...I DID IT!!!"
Dose 19 = 3/15/2013
   During the first week following this infusion I had tender cheeks and gums, such that brushing my teeth was very painful.  I was awakened three days later with mouth pain.  My tongue was raw with deep painful lesions underneath.  Shoulders, elbows, and wrists were sore.  In one more week I was wheezing badly, my nurses were quite alarmed (as always...don't know why we can't get used to the cycle!!!) and urging me to take a Decadron shot.  No can do!!  But, with nebulized albuterol and atrovent, and an increased dose of my symbicort, I gradually got better.  Vitiligo continued to increase and I posted another set of pics on the blog.  By May 20th my tongue was raw with a host of new lesions.  It had been getting better!!!!  What the tub?????
Dose 20 = 6/7/2013...2 1/2 YEARS on anti-PD1...LAST DOSE!!!!!
   Got confirmation at this visit that no more peptide vaccines would be used at Moffitt as a treatment strategy.  Weber was duly impressed by my mouth lesions.  On the 8th I noted, "Extremely tired this morning with anti-PD1 aches in my ankles, knees and toes and road rash on my tongue."
   In August, the arthralgias had abated.  Mucositis with mouth and tongue ulcerations, bleeding gums, tender lips....had demonstrated NO improvement.
Recheck after completion of meds =  9/13/2013
   Learned that I was the ONLY patient out of 120 who had developed mouth ulcers.  Others had developed sore, tender gums and mouth with mucositis...but no ulcers!!!  So, there's hope for the rest of you!!!  Anyhow, though Weber (and my dentist) continued to be very impressed/aghast with the ulcers remaining after treating with Peridex and 24 hours worth of Valcyclovir...I am happy since they are ever so much better and almost pain free.....finally.  Weber also spontaneously noted that my vitiligo had continued to increase since my last visit.
Note:  There has been some discussion in the press, on boards and with Dr. Weber regarding 5 patients out of the 120 in my study who developed shingles.  The jury is still out on whether that is a direct result of anti-PD1, since the age of most of the patients in the study is such that they are the folks who would be most likely to contract shingles with anti-PD1 or without it.
TODAY
   Feeling well. Running 3-4 miles at least 3-4 times a week...occasionally more often.  My mouth ulcers remained minimal for about 4 weeks, but then began to rear their ugly head again.  Restarting the antibacterial mouth wash did nothing to help.  Currently, they are not as bad as they had been, but I do have a fairly large eroded place with exudate to both sides of my inner cheeks by my molars and under my tongue is raw, red, and tender.  Perhaps the meds that I thought so highly of did nothing, and it was just time for the lesions to wane.  OR.....perhaps I HAD developed a secondary infection in the lesions since they had been there for over 4 months...nonstop....that the meds did help with...and this is just another anti-PD1 flare, with no infection.  Just anti-PD1.  Doing its thing.  In the words of Weber...."This stuff is WEIRD!!!"

Best. - c