Get out and enjoy!

As most of you know I spend most of my free time outdoors. With the weather finally getting nice you would be hard pressed to to catch Nicki or me inside. Well for the the past 4 days I have stayed in the house. The price you pay with fighting this disease is being tired all the time and dealing with all of the side effects of the drugs. This morning was no exception, I felt like the only thing I wanted to do was stay in bed.
The mind is the most powerful part of our bodies. I told Dan we would try to meet for lunch but my body said no way. Cut to the chase, after a few minutes of my mind telling my body that we were going out and that it was in control, and I was not going to stand for this today - I dressed and Nicki drove me to Dan and Whitney's house.
I got out. My mind won and won for the good. It was great getting out for a few hours, make sure you do the same. Let your mind tell your body what to do. It works.

See you tomorrow.

Mark

One Thousand Two Hundred Sixty Five

That is the number of times people have read the blog in the last 2 weeks- 1,265. I find that to be, at first unbelievable, but when I consider the type of people that I have known, I understand. You are the most caring, concerned friends, and family a person could ever have and I am forever grateful.

Jeremy and Dan are trying hard to keep it as interesting as possible and provide all of you with as much information as they can. Since I am not allowed to thank them ( I have been told) I guess I can tell them how proud I am of them.

Many of you have asked how I am feeling and I chose not to make this a "How is Mark Today" Blog. Just to make it easier for all concerned, some days better than others but nothing I can't
handle. You just have to adjust, enough about me.

Once again thanks for the support. Nicki sends her love to all and continues to bring cheer into my life.

Looking forward to tomorrow


Mark

Bracelet Donations

Good morning!

As Jeremy posted several days ago, we have designed bracelets similar to the Lance Armstrong LIVESTRONG bracelets. We have already given out the first order of 75 that we received last week. Since they were such a huge hit or since people felt so inclined to support my father, we have decided to order 100 more.

Many people have been asking us how much they cost and our primary intention was just to give the bracelets to those that wanted to express their support. Jeremy and I have decided to let you determine how much (if anything), you would like to donate to the cause. We thought it would be most appropriate to have donations go to the Memorial Sloan-Kettering Cancer Center, since they are treating my father and have been nothing less than amazing. This link will take you directly to the donations page where you can select what cause you want to donate to, preferably Melanoma. Any donation is greatly appreciated.

Click here to donate to Memorial Sloan-Kettering Cancer Center

If you have not received one and would like one, please let one of us know and we can either try to mail them to you or work out a way to meet you.

Thanks again for all your support.

A New Cheerleader

My Dad has a new cheerleader - meet Junior - scheduled to arrive sometime around November 8th.

Today is my birthday !

Before you begin to read this I want you to know it is from Nicki, she has a problem with her password so she is using mine.


Today is my birthday. I've been putting off writing on Mark's blog, mostly because I was concerned that I wouldn't be able to know the right things to say. I'd like to be clever and profound and express myself in the most meaningful way; however, I'm not sure if that moment will occur so,"Carpe Diem", seize the day!

Today is my birthday. Even with our current circumstances I feel that I am blessed. I have the love and devotion of friends and family, the prayers and sincere thoughts of those people who have recently become friends, and of course I have "The Love of My Life" alongside me.

Today is my birthday. With everyone's help, prayers, and positive energy my "Knight in shining armor"will defeat his enemy.

Please continue to make my greatest wish come true.

I want everyone to accept my most sincere gratitude and love.

Nicki

A quick note of thanks

It is the most amazing feeling to have all of the notes, cards, phone calls e mails etc. that I have received over the past few weeks. I have spoken to people I havn't spoken to in over 20 years. I have had such warm conversations with people I speak to everyday and just have taken that for granted. I would never have imagined that I would have gotten this much attention but I must say I love it. I can never be able to respond to all of you in the way in which you have gotten in touch with me but I really just want to say I love you all and thanks for the support . You will never know what it really means to me and my family. We all thank you so much.

Canine treatments may shed light on cancer

An article in the Los Angeles Times includes an interview with my father's doctor Dr. Wolchok, who is one of the lead investigators on a project that is developing a vaccine for a canine melanoma. This research will hopefully provide further understanding into the treatment of humans with melanoma.

They can sit, and stay, and fetch. They can sniff out drugs, guide the blind, dial 911.

Maybe they can even cure cancer — or help cure it, anyway. Many scientists see cancer in dogs as an excellent model for cancer in humans, and evidence is growing that they're barking up a very useful tree.

Late last month, a vaccine to treat canine melanoma won conditional approval from the U.S. Department of Agriculture — the first time the government has approved a therapeutic vaccine for treating cancer in either animals or people. And trials are underway on a similar vaccine to treat melanoma in people.

Read the rest of the article here.

A wake up call

Over the past few weeks I have had the conversation with my family about how we never know what the future holds. Upon my learning of my condition the thing we spoke about is the fact that you never know what is in store for you or your loved ones. Make today count.

Having time on my hands I got to watch TV and spent the day watching the scenes from Virginia Tech.

Make each day count, you never know what the future holds.

Looking forward to tomorrow

Regards


Mark

Food Recommendations?

My dad has been feeling pretty nauseous lately - does anyone have any recommendations for foods he should try? He had a craving for blueberry blintzes recently...

Something to think about!

Just came back from Sloan for my one week evaluation. For the first time I have started to have reactions from the drug. All along they told me I would. At this point it is a rash on my face, neck, scalp, etc. as well as feeling more nauseous than usual. Speaking to my nurse (who really knows everything) she expressed how glad she was because it meant that since it was causing those reactions it was also engaging the melanoma cells.

The question is - do I want to get sicker and feel like the fight is really on or do I hope for a round at a time and beat it in 12 rounds?

Since I don't have control I go with whatever comes my way. But it is something to think about.


Looking forward to tomorrow

Regards

Mark

Array BioPharma achieves milestone

Array BioPharma achieves milestone for dosing MEK inhibitor

Saturday, April 14, 2007 14:00 IST
Boulder, Colorado

AstraZeneca PLC dosed its first cancer patient in a phase 1 clinical trial with our MEK inhibitor, ARRY-704 (AZD8330), triggering a $2 million milestone payment from AstraZeneca to Array BioPharma Inc. In December 2003, Array partnered the oncology portion of its MEK programme, including its lead compound, ARRY-886 (AZD6244), for co-development and commercialisation with AstraZeneca.

The collaboration included research and development of additional clinical candidates, which resulted in the selection of ARRY-704 in December 2005.

ARRY-704 is a potent, selective, orally active MEK inhibitor that blocks signal transduction pathways implicated in cancer cell proliferation and survival. ARRY-704 has shown tumour suppressive activity in multiple preclinical models of human cancer including melanoma, pancreatic, colon, lung, and breast cancers.

More Success in Another AZD6244 Trial

Researchers at the National Cancer Centre of Singapore have had a successful trial for another type of cancer commonly found in Asia and Africa (I've highlighted the important parts):

Hepatocellular carcinoma (HCC) is a common malignancy in Asia and Africa. We previously reported that overexpression of extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) and ERK1/2 was detected in HCC, and that their activation was required for liver cancer cell proliferation and survival. In the present study, we determined the efficacy of a specific MEK1/2 inhibitor AZD6244 (ARRAY-142886) in treatment of HCC. Treatment of primary HCC cells with AZD6244 led to growth inhibition, elevation of the cleavage of caspase-3 and caspase-7, and cleaved poly(ADP)ribose polymerase, but inhibition of ERK1/2 and p90RSK phosphorylation. Studying the protein expression profile of seven HCC xenografts revealed that their growth rate was positively correlated with the levels of phosphorylated MEK. AZD6244, when given p.o. to mice bearing these xenografts, resulted in a dose-dependent inhibition of tumor growth. AZD6244-induced growth suppression was associated with inactivation of ERK1/2 and p90RSK, and up-regulation of activated caspase-3 and caspase-7, and cleaved poly(ADP)ribose polymerase. Our data suggest that the MEK-ERK pathway plays an important role in the growth and survival of liver cancer cells and that the HCC xenograft models are excellent tools for screening preclinical drugs. Targeted inhibition of the MEK-ERK pathway with AZD6244 may represent an alternative approach for the treatment of this disease.

Thanks for all the responses

I received a number of replies today. Thanks to all of you who responded, as well as to all of you who just read the blog.
I did receive a response from a person who will be starting the drug this Tues. She wishes to stay out of the blog but I have started to email her. This in itself has made the whole blog worthwhile. She is from the south and emailing her has helped both of us more than you can imagine.

Once again thanks for all of your support

Looking forward to tomorrow


Mark

CONVERSATIONS WITH MYSELF

If you can't be honest with yourself now, when can you be? Throughout life how many times do you look in the mirror while shaving or putting on makeup or getting dressed and talked to yourself?

Gee, I look good or I really need to get my haircut or that tan makes me look younger (sexier).
I guess it has occurred thousands of times and most of the time I wasn't even aware of it.

Now a look in the mirror tells a whole new story. In a few seconds the most important parts of my life get played out. The strange part is that two scenarios always occur. The first is Lets Make a Deal. I will do that - if I can have that. I guess that falls into the spiritual side.

The other scene is the one of me looking into the mirror, cursing up a storm and telling the cancer I will kick its ass and it does not know who it is messing with. I guess that's my competitive side.

Either side allows me to win so I will continue to look in the mirror and have those conversations with myself.

I suggest that you do as well, it really makes you feel better


Sorry for missing a day but I look forward to tomorrow.

Mark

Posting Comments (updated)...

I know many of you have had trouble posting comments to this blog, so here are step-by-step instructions:

In order to post comments, you must have a Google account - the easiest way to get one is to sign up for GMail - Google's free email service. Sign up here.

Once you have an account, you can follow the rest of the directions below:

Find the "comments" link at the end of each post, like this:

If you click this link, you will go to the comment posting page.

The comment posting page looks like this:

In the upper left corner, there is an option to show or hide the original blog post that the comments relate to. The rest of the left-hand column contains any comments that have already been made.

On the right hand side of the page is the space for you to enter your comment. Beneath that are the identity options. If you already have a Google account, you can use the same log-in information - otherwise you will be asked to set up a new account in order to post a comment.

I know its a hassle to register, but it prevents spam from getting into the comments.

If you have any trouble, please let one of us know.

The Median Isn't the Message...

by Stephen Jay Gould

My life has recently intersected, in a most personal way, two of Mark Twain's famous quips. One I shall defer to the end of this essay. The other (sometimes attributed to Disraeli), identifies three species of mendacity, each worse than the one before - lies, damned lies, and statistics.

Consider the standard example of stretching the truth with numbers - a case quite relevant to my story. Statistics recognizes different measures of an "average," or central tendency. The mean is our usual concept of an overall average - add up the items and divide them by the number of sharers (100 candy bars collected for five kids next Halloween will yield 20 for each in a just world). The median, a different measure of central tendency, is the half-way point. If I line up five kids by height, the median child is shorter than two and taller than the other two (who might have trouble getting their mean share of the candy). A politician in power might say with pride, "The mean income of our citizens is $15,000 per year." The leader of the opposition might retort, "But half our citizens make less than $10,000 per year." Both are right, but neither cites a statistic with impassive objectivity. The first invokes a mean, the second a median. (Means are higher than medians in such cases because one millionaire may outweigh hundreds of poor people in setting a mean; but he can balance only one mendicant in calculating a median).

The larger issue that creates a common distrust or contempt for statistics is more troubling. Many people make an unfortunate and invalid separation between heart and mind, or feeling and intellect. In some contemporary traditions, abetted by attitudes stereotypically centered on Southern California, feelings are exalted as more "real" and the only proper basis for action - if it feels good, do it - while intellect gets short shrift as a hang-up of outmoded elitism. Statistics, in this absurd dichotomy, often become the symbol of the enemy. As Hilaire Belloc wrote, "Statistics are the triumph of the quantitative method, and the quantitative method is the victory of sterility and death."

This is a personal story of statistics, properly interpreted, as profoundly nurturant and life-giving. It declares holy war on the downgrading of intellect by telling a small story about the utility of dry, academic knowledge about science. Heart and head are focal points of one body, one personality.

In July 1982, I learned that I was suffering from abdominal mesothelioma, a rare and serious cancer usually associated with exposure to asbestos. When I revived after surgery, I asked my first question of my doctor and chemotherapist: "What is the best technical literature about mesothelioma?" She replied, with a touch of diplomacy (the only departure she has ever made from direct frankness), that the medical literature contained nothing really worth reading.

Of course, trying to keep an intellectual away from literature works about as well as recommending chastity to Homo sapiens, the sexiest primate of all. As soon as I could walk, I made a beeline for Harvard's Countway medical library and punched mesothelioma into the computer's bibliographic search program. An hour later, surrounded by the latest literature on abdominal mesothelioma, I realized with a gulp why my doctor had offered that humane advice. The literature couldn't have been more brutally clear: mesothelioma is incurable, with a median mortality of only eight months after discovery. I sat stunned for about fifteen minutes, then smiled and said to myself: so that's why they didn't give me anything to read. Then my mind started to work again, thank goodness.

If a little learning could ever be a dangerous thing, I had encountered a classic example. Attitude clearly matters in fighting cancer. We don't know why (from my old-style materialistic perspective, I suspect that mental states feed back upon the immune system). But match people with the same cancer for age, class, health, socioeconomic status, and, in general, those with positive attitudes, with a strong will and purpose for living, with commitment to struggle, with an active response to aiding their own treatment and not just a passive acceptance of anything doctors say, tend to live longer. A few months later I asked Sir Peter Medawar, my personal scientific guru and a Nobelist in immunology, what the best prescription for success against cancer might be. "A sanguine personality," he replied. Fortunately (since one can't reconstruct oneself at short notice and for a definite purpose), I am, if anything, even-tempered and confident in just this manner.

Hence the dilemma for humane doctors: since attitude matters so critically, should such a sombre conclusion be advertised, especially since few people have sufficient understanding of statistics to evaluate what the statements really mean? From years of experience with the small-scale evolution of Bahamian land snails treated quantitatively, I have developed this technical knowledge - and I am convinced that it played a major role in saving my life. Knowledge is indeed power, in Bacon's proverb.

The problem may be briefly stated: What does "median mortality of eight months" signify in our vernacular? I suspect that most people, without training in statistics, would read such a statement as "I will probably be dead in eight months" - the very conclusion that must be avoided, since it isn't so, and since attitude matters so much.

I was not, of course, overjoyed, but I didn't read the statement in this vernacular way either. My technical training enjoined a different perspective on "eight months median mortality." The point is a subtle one, but profound - for it embodies the distinctive way of thinking in my own field of evolutionary biology and natural history.

We still carry the historical baggage of a Platonic heritage that seeks sharp essences and definite boundaries. (Thus we hope to find an unambiguous "beginning of life" or "definition of death," although nature often comes to us as irreducible continua.) This Platonic heritage, with its emphasis in clear distinctions and separated immutable entities, leads us to view statistical measures of central tendency wrongly, indeed opposite to the appropriate interpretation in our actual world of variation, shadings, and continua. In short, we view means and medians as the hard "realities," and the variation that permits their calculation as a set of transient and imperfect measurements of this hidden essence. If the median is the reality and variation around the median just a device for its calculation, the "I will probably be dead in eight months" may pass as a reasonable interpretation.

But all evolutionary biologists know that variation itself is nature's only irreducible essence. Variation is the hard reality, not a set of imperfect measures for a central tendency. Means and medians are the abstractions. Therefore, I looked at the mesothelioma statistics quite differently - and not only because I am an optimist who tends to see the doughnut instead of the hole, but primarily because I know that variation itself is the reality. I had to place myself amidst the variation.

When I learned about the eight-month median, my first intellectual reaction was: fine, half the people will live longer; now what are my chances of being in that half. I read for a furious and nervous hour and concluded, with relief: damned good. I possessed every one of the characteristics conferring a probability of longer life: I was young; my disease had been recognized in a relatively early stage; I would receive the nation's best medical treatment; I had the world to live for; I knew how to read the data properly and not despair.

Another technical point then added even more solace. I immediately recognized that the distribution of variation about the eight-month median would almost surely be what statisticians call "right skewed." (In a symmetrical distribution, the profile of variation to the left of the central tendency is a mirror image of variation to the right. In skewed distributions, variation to one side of the central tendency is more stretched out - left skewed if extended to the left, right skewed if stretched out to the right.) The distribution of variation had to be right skewed, I reasoned. After all, the left of the distribution contains an irrevocable lower boundary of zero (since mesothelioma can only be identified at death or before). Thus, there isn't much room for the distribution's lower (or left) half - it must be scrunched up between zero and eight months. But the upper (or right) half can extend out for years and years, even if nobody ultimately survives. The distribution must be right skewed, and I needed to know how long the extended tail ran - for I had already concluded that my favorable profile made me a good candidate for that part of the curve.

The distribution was indeed, strongly right skewed, with a long tail (however small) that extended for several years above the eight month median. I saw no reason why I shouldn't be in that small tail, and I breathed a very long sigh of relief. My technical knowledge had helped. I had read the graph correctly. I had asked the right question and found the answers. I had obtained, in all probability, the most precious of all possible gifts in the circumstances - substantial time. I didn't have to stop and immediately follow Isaiah's injunction to Hezekiah - set thine house in order for thou shalt die, and not live. I would have time to think, to plan, and to fight.

One final point about statistical distributions. They apply only to a prescribed set of circumstances - in this case to survival with mesothelioma under conventional modes of treatment. If circumstances change, the distribution may alter. I was placed on an experimental protocol of treatment and, if fortune holds, will be in the first cohort of a new distribution with high median and a right tail extending to death by natural causes at advanced old age.

It has become, in my view, a bit too trendy to regard the acceptance of death as something tantamount to intrinsic dignity. Of course I agree with the preacher of Ecclesiastes that there is a time to love and a time to die - and when my skein runs out I hope to face the end calmly and in my own way. For most situations, however, I prefer the more martial view that death is the ultimate enemy - and I find nothing reproachable in those who rage mightily against the dying of the light.

The swords of battle are numerous, and none more effective than humor. My death was announced at a meeting of my colleagues in Scotland, and I almost experienced the delicious pleasure of reading my obituary penned by one of my best friends (the so-and-so got suspicious and checked; he too is a statistician, and didn't expect to find me so far out on the right tail). Still, the incident provided my first good laugh after the diagnosis. Just think, I almost got to repeat Mark Twain's most famous line of all: the reports of my death are greatly exaggerated.

Stephen Jay Gould died on May 20, 2002 - 20 years after being diagnosed with a disease that had a "median life expectancy" of 8 months...

Melanoma Clinical Trials

Its amazing how many trials are being conducted for the treatment of melanoma. The Melanoma Research Foundation keeps a list of all active trials.

Its important that we keep an eye on these so that we are aware of additional options in the future. If anyone knows people who are involved in any trials of melanoma treatments, we'd love to hear about it.

Just a fast note.

We had 21 people read the blog the first day and over 40 by day two . Not bad for a pop and sons page(really all sons and very little pop) I guess the real point here is if anyone who reads it can possibly send it on to at least one other person, in a very short period of time it will really do what it was intended to do, and that was to share the info. and in some way help someone.

Looking forward till tomorrow .

AZD4622 Presentation

I found this presentation to be very helpful in really breaking down what the drug does and how it works. I have to admit that I probably only understood 5% of all the information but there are some good graphs to check out. Those that have a scientific background it may be more useful to you. Please feel free to check the link below whch will direct you to the PDF presentation.

http://danielslevine81.googlepages.com/PubAttachment179.pdf

Melanoma Awareness Bracelets

Dan and I ordered some bracelets (similar to the LIVESTRONG bracelets) - Black is apparently the color for melanoma awareness.

They should be in on Monday - let us know if you would like one.

AstraZeneca Business Review

I stumbled upon some interesting information that is available on the web - the 2006 AstraZeneca business review. It covers the drugs they have in their pipeline and the findings of any studies so far. Much of it is too scientific for me to understand, but there is definitely some interesting information. It really seems like there is confidence in the MEK inhibitor as the future of cancer treatment.

You can check out the document here - 2006 Business Review.

Whats going on inside?

I just took my sixth treatment of AZ6244 and like all the others it went down just fine. The question I have is what is going on inside. I wish I could just take a look.Wouldn't it be great to see how the cancer cells are reacting to the drug? If they had a reaction would it be better to double up?
I guess I have to wait the 6 weeks until my scans show what is going on. Is this a thought that others have had or is it just a childish Barbarella fantasy?

This blog is really therapeutic since I think of it often and look forward to reading and writing in it.

I thank my two sons for creating it and urging me to take part in it. Hopefully others will join in.

Look forward to entering it again tomorrow.

Sharing is Caring

My 2 year old niece says it best, "Sharing is Caring." I am sure all of us learned this when we were a similar age, but holds true to me more now than ever before. Just to reiterate what my father said, this site is not just about him or just for him, it is for all those experiencing something similar to what we are. When I say we, I mean those that have melanoma, those that have a colleague, friend, or family member that has cancer and are just looking to share their experiences (good or bad) with others who are going to listen. After all, the Internet was primarily created to disseminate and share scientific and medical information among scientists, doctors, and researchers. Let's get back to its intended use!

Its not about me!

Well I am Jeremy's and Dan's father. When reading the Blog you understand real quickly that it is not about me but it is about life and the desire and want to live. It is about family, friends business associates and everyone who has stopped by for a moment in my life. The all have one dream and that is to help me and therefore help anyone else who has the disease and may have the chance through AZD 6244 to get better.

I am looking to share my story with others who have taken or are about to take the drug with the same hopes and dreams as I have. Since it is only day 2 of course there are no results yet but at least I can say the first 4 treatments have gone well. The taste of the drug is fine and the process is easy to do. So far so good. I visualize with every sip of the drug that as it is going down the cancer cells are eating it up and dying off as if the were leaves on a tree as winter arrives or as I say to my wife a Pac Man game eating away at the enemy.

I will on a daily basis keep who ever reads this informed. I hope others will join me, we can all grow from the experience as well as help others.

I look forward to tomorrow more than ever before. See you then.

Research Report on Array BioPharma (ARRY)

WR Hamrecht has a research report on ARRY (the company the produces AZD6244) which shows there is significant momentum around the success of this drug. In fact the target price was almost doubled in November based on potential of AZD6244 and the results of the trial my father is participating in.

AZD6244

The main reason we decided to start this blog is to see if we could connect with others that are in similar trial with experimental medications fighting melanoma and try to share information.

My father was selected to participate in a trial with the drug AZD6244 which is a selective MEK inhibitor developed by Array BioPharma and licensed by AstraZeneca. The theory behind the drug is that it can block a protein that the cancer cells need to grow and survive.

He started the drug yesterday - we would love to share experiences with anyone else out there who is also taking this drug or has taken it in the past.

The Specialist

My father was referred to a melanoma specialist at Sloan-Kettering - Dr. Jedd Wolchok.

Dr. Wolchok did an examination and told us the most comforting thing that we had heard so far - that each case should be treated as an individual - ignore what you read or what you've heard, and that as doctors they have seen amazing things.

Next he suggested that my father should enter into a phase II trial with an experimental drug - AZD6244. The trial randomly selects people to either take the AZD6244 (an experimental medicine) or Temozolomide (a chemotherapy drug).

After a ton of paperwork he was officially a lab rat (pending a whole bunch of tests)!

Discovery of the melanoma

My father was having lots of pain radiating from his waist up. Many doctor's appointments later and many tests later - the doctors couldn't find anything.

A friend of my father's (a doctor) suggested that he get a CT Scan of his chest. His insurance company initially rejected the test, calling it unnecessary. My dad's friend actually took the time to call the company and speak directly to one of the doctors there and convinced him to allow the test.

Shortly after the test, the radiologist and his doctor let him know that they had found several lesions - on his bones and some of his organs. We were blown away (obviously). My dad is one of the healthiest guys I know - he hasn't eaten red meat in 25 years, works out all the time, doesn't smoke, etc...

We are very fortunate to have a family friend who is an oncologist at Memorial Sloan-Kettering Cancer Center - he was able to see my dad immediately and began to perform all of the standard tests to determine the type of cancer and try to locate the primary location.

All the tests turned up negative - the doctors were stumped. So the doctor sent my father to get a biopsy on his liver, where one of the lesions were located. The results of that test finally showed that it was a melanoma.

What is Stage IV Melanoma?

Very simply, melanoma is skin cancer and phase IV means that is has spread to other areas of the body, such as bones, organs, and lymph nodes far away from the original tumor.

When cancer gets to this point the consensus is that its "incurable."

The American Cancer Society has a breakdown of the treatment of Melanoma by stage.

In my father's case, they could not locate the "primary" location of the cancer.

Welcome

My brother and I are starting this blog as a central place to share information about the progress of our father who is fighting stage IV melanoma.

We'd like to try and reach others who are also fighting stage IV melanoma.