Sometimes the battle against NET frustrates me so badly I want to quit.

Today is one of those days. It is the result of a week of grinding on things and feeling that for all I have read and thought about and written I am doing far too little good for the time spent.

Two days ago I wrote a post on NET research. Two people have read it. Yesterday, I wrote about the need to fund basic research. Three people read that–and no one reacted to it.

Ten days ago, the local paper ran a story on my Jimmy Fund Marathon Walk effort. There was a bump in visits to this site–and one person commented on the story on the newspaper’s site, but that was the total reaction to the piece.

Jane’s death was 19 months and 15 days ago. Every day it feels like another part of my soul is gone–eaten by the grief and my seeming inability to bring about any kind of real change. People are still diagnosed with NET as poorly as they were two years ago. We still have no way to cure the disease after its initial stage–nor anything on the drawing board that looks likely to do that.

The NET money puzzle is every bit as inadequate as it was two years ago–and while we have added a few dollars to the pie, it is still woefully inadequate–and my efforts have had very little–if anything–to do with any of it.

I have ideas, but not the resources to carry them out as I would like to. We  have an electronic storefront that few visit–and that no one has purchased anything from for months. I have a direct mail letter finished but find the idea of stuffing and addressing 500 envelopes overwhelming. The same goes for a letter looking for companies to sponsor the Marathon Walk t-shirt.

My to-do list grows every day but the results list is largely stagnant.

This is not, however, the sound of me giving up. I played hooky most of today in the hope a day away from the madness would improve my state of mind. It has, but I am still feeling pretty frustrated. Hopefully, another good night of sleep tonight will help.

But I begin to understand the frustration others who have been fighting this disease longer than I have feel. Gaining any kind of traction when most of the world has never heard of NET or CS seems nearly impossible.

Still, I am reminded of the motto of the Skunkworks–the lab that designed US planes for World War II: “The difficult we do immediately; the impossible takes a little longer. And I am also reminded of President Kennedy’s statement about going to the moon: We do not do this because it is easy but because it is difficult.

So I will go back to work tomorrow. I’ll stuff envelopes and make lists and draft new appeals. I’ll keep trying. Doing nothing changes nothing. Change only happens when we work to bring it about.

Reading the review paper on NET research that I summarized here yesterday, I was struck by how many of the drugs under study have already been approved for other cancers and diseases. It is something I’ve known for a long time, but reading the full listings yesterday really brought it home to me what it means to be an orphan disease.

What an orphan gets

Like human orphans, orphan disease patients too often end up with the hand-me-downs and the leftovers. Even octreotide, the NET standby, was developed as a way to help chemo-therapy patients tolerate the side-effects of their treatments. That it happened also to have an impact on NET carcinoid syndrome symptoms and slowed the progression of that disease was little more than a happy accident that boosted the drug maker’s bottom line for the drug.

But from a drug company’s point of view there is no real profit in developing drugs whose initial purpose is to deal with NETs. Drugs for NET are not a multi-billion dollar market–at least not yet.

And neither drug companies nor the federal government have much interest in funding research on anything they are not virtually certain will work before the first experiment they pay for is run. For a drug company, an experiment that does not lead to a profit fairly quickly is not one they are overly interested in funding.

Government, too

The federal government’s interest in nearly certain success comes from a concern over being seen as spending taxpayer dollars foolishly. NBC’s Fleecing of America stories sometimes bother me because they can be overly critical of government spending on pure science. Senators, congressmen, and reporters all seem to want every dollar to have an immediate return. Having hung around with science and engineering folk for most of my life, I know that an immediate concrete return on research and development spending does not always happen.

Without events like the Pan-Mass Challenge, the WEEI/NESN Jimmy Fund Radio-Telethon, and the Jimmy Fund Marathon Walk the money to do the fundamental medical research neither drug companies nor governments will fund would not happen. The lines of NET cells now growing in vitro would not exist without that money. The progress made this year toward an animal model for NET would not exist without that money. The NET patient genome study currently underway would not exist without that money. Our knowledge of which receptors to target would not exist without that money.

We can do better

The Dana-Farber Cancer Institute is like every other cancer research center in the country. They all have events like the Marathon Walk to provide them with the money they need to do the research that has to be done before government or private enterprise will get involved.

Our Marathon Walk team is designed to generate that seed money from which a strong Program in Neuroendocrine and Carcinoid Tumors can grow. But we need your help, both as donors and as walkers if we are going to get NET out of the orphanage.

NET research review paper published.

Oncology, one of the big names in cancer research publications, published a new review article on the state of NET Research July 12.

A link to the full text of the article is also available on the Medical Reading page. What follows is my summary of the article’s contents aimed at a “civilian” audience.

The article by Boris G. Naraev, Jonathan R. Strosberg, and Thorvardur R. Halfdanarson examines a number of research studies that show a number of new therapies on the horizon for treatment of both pNETs and Carcinoid tumors. Some of these grow out of an improving understanding of how cancer in general–and NETs in specific work.

On such pathway is the mammalian target of rapamycin (mTOR) receptor. Everolimus targets this particular pathway. It has already been approved by the FDA for use in pancreatic NETs and is currently being studied for carcinoid tumors, in particular in combination with octreotide LAR (somastatin), the current go-to drug for most NETs. The results of that Phase III trial were a 16.4 month progression free median survival rate as opposed to 11.3 months for octreotide and a placebo. It improved median progression free survival in  pNET patients by 6.4 months.

Everolimus is also under study with other drug combinations, particularly for pNET.

VEGF Pathway Drugs

VEGF helps regulate the formation and growth of new blood vessels. Tumors hijack it to grow themselves a blood supply. Prevent that from happening and you can stop a tumor cold–at least theoretically. There are three different VEGF receptors. The important one in tumor formation appears to be VEGFR-2. Two different approaches can be used to control it: blockers, such as bevacizumab and tyrosine kinase inhibitors (TKIs). Among these are sunitinib, pazobanib, and sorafenib. Trials are underway on all four drugs.

A Phase II trial of 44 patients looked at bevcizumab in combination with octreotide. That combination seems to be promising, according to the review, but the trial is not yet complete. Twenty-seven of the 44 patients in the study were still alive after three years.

A number of other trials are ongoing with a variety of other drugs.

The most important for patients, however, is a large Phase III trial of bevcizumab and octreotide LAR. The Southwest Oncology Group trial has an estimated enrollment of 400 patients. That trial may still be accepting patients. Check www.clinicaltrials.gov under NCT00569127 or SWOG S0518).

Sunitinib

Sunitinib targets multiple TKIs. It is more effective against pNETs than against carcinoids, according to the review. It may also be useful in combination with hepatic artery embolization for pNETs that have metastasized to the liver. A Phase III showed it more than doubled median progression free survival versus a placebo (11. 4 months versus 5.5 months). The FDA approved the drug for pNET in May 2011.

Pazopanib and Sorafenib

Pazopanib plus octreotide LAR had a 17 percent response rate in a Phase II trial among pNET patients but no effect was seen in patients with carcinoid tumors. About 10 percent of both NET and pNEt patients responded to sorafenib as a single agent in a Phase II trial. However, 43 percent experienced significant toxic effects. A Phase II study of sorafenib with beacizumab was more promising.

Somastatin Receptors

Somastatin is involved in a number of things involving the way the body works. It has also long been the key to how we treat neuroendocrine tumors. This is because about 80 percent of NETs and carcinoid tumors have one or more of five possible somsatin receptors: SST1, SST2, SST3, SST4, and SST5.

Octreotide, the drug Jane was on, binds very well to SST2 and somewhat to SST5. It does a good job for many patients in controlling the diarrhea and flushing that go along with carcinoid syndrome.

It has now, however, been shown to slow the progression of the disease–14,6 months versus 6 months on a placebo.

Laneotride does the same job octreotide does but has a much longer half-life.

Pasireotide

When octreotide LAR fails, pasireotide is effective for 27 percent of those patients. It binds as effectively to SST2 as octreotide but binds 40 times more effectively to SST5, 30 times more effectively to SST1 and five times as effectively to SST3. It has to be injected twice a day, however.

A study (Phase III) comparing the LAR forms of the two drugs has been terminated.

PRRT

Studies of Peptide Receptor Radionuclide Therapy in Europe have resulted in considerable buzz in the United States. But even in Europe, where the treatment has become common, response rates vary from four percent to 35 percent. However, those who do respond to the treatment do have improved survival. Currently, two different sources of radiation are being used: lutetium-177 and yttrium 90. Indium-111 was in use at one point but is now rarely used. No trials comparing the use of the other two have been done. The technique has not been FDA approved in the US.

There was a study being planned in the US, but the paper makes no mention of it.

Other Therapies

The paper looks at a number of other drugs and pathways, including an epidermal growth factor receptor phase II trial of gefitinib, the IGF-1R pathway and AMG479 and cixutumumab, the histone deacetylase pathway, protein degradation pathways, immunomodulating therapy using thalidomide, and c-kit and PDFGR pathways, but all those techniques are in Phase I or II trials with very few patients involved at this point.

In light of the shootings in Aurora, Colorado early this morning there will be no new postings made to this site today or this weekend. Please take time to be with your families and friends. Give them all an extra hug and an extra kiss. Death comes in too many forms–and too often we never see it coming.

Tell people you love them today.

“He says he thinks it’s cancer,” she said. “He said they can’t be sure until after the biopsy…”

She was upbeat. She was positive. But the word cancer was still there.

That was two years ago. It was, at that moment, the worst thing that had ever happened to us. Worse was coming but we both put the best spin on it we could. We tried to be strong for each other.

I woke up to that memory this morning. It haunted me through breakfast, through the dishes, through the morning tour of the garden. I don’t want to remember but I can’t stop. I want to go home but I can’t. The place that was home–the place I am writing this from–ceased to be home when she wasn’t here anymore. Now it is a house on a hill, no more a home than anywhere else I lived before we married. It is the place I sleep, the place I eat, the place I work.

Our books are here. Our furniture is here. Our dishes are here. But they are mere objects and reminders of who we were together.

There is a card Jane gave me on one of our early anniversaries on the book-case to my right. “Who, being loved, is poor?” It has been on my bookcase, no matter where we were, since the day she gave it to me. It was one of the first things I unpacked when we moved into this house nearly 18 years ago.

By that measure, I am wealthy beyond the wildest dreams of avarice. But today it is as though all that wealth is tied up in things that make it untouchable. I am at once the wealthiest man in the world and the poorest.

Death is a felon–and Cancer is his most sadistic partner. There are no nice cancer deaths. Each is wrapped in a unique and searing bubble of mental, physical, and emotional pain. And the pain is not singular. It ensnares not only the patient who physically has it but the people who love them as well.

In the obituaries they use the term “survived by.” The reporters who write those words have no idea how ironic that phrase is. Nor do those who have not experienced this kind of deep personal loss. The word is totally appropriate–not as a euphemism but as a real description of the status of those left behind. We have survived. But survival is not exactly the same as living. We are ships with neither rudders nor anchors in waters infested with reefs, rocks and shallows that can hole a fragile hull in an instant.

People ask why I do what I do. They ask why I don’t just move on. They ask why, 19 months and nine days after my wife’s death, I still wear my wedding ring.

I still love my wife. I want you to continue to love your spouse. But I want you to have that person physically with you.

I have survived a great shipwreck–the greatest shipwreck imaginable. I want to make our ships safer.

My days are filled with cancer this week–and NET cancer in particular. Monday, the Herald News piece on our Marathon Walk effort ran. That same day a friend lost her mother to another, but equally nasty, cancer. Yesterday we put the finishing touches on a direct mail letter, designed a t-shirt, reached an agreement on our Marathon Walk team, and the Herald News posted a video of me talking about the Marathon Walk.

This morning I tried to get a training walk in but quickly gave that up when I saw that it was already 85 at 7 a.m. We will not discuss the humidity–which made every step feel like I was doing it under water.

Later I met for two hours with two

members of our press group to talk about this year’s press kit for NET Cancer Awareness Day on November 10. While we will be doing some follow-ups on stories from last year ,we hope to have two blockbuster pieces–one of which will be fairly light but the other of which will attempt to answer some difficult questions. I won’t go into detail on any of those pieces at this point because in the news business you never know which stories will pan out and which won’t. But I hope to whet your appetite somewhat.

I am continuing to work my way through the latest presentations and research and later this afternoon will post a link to the slides of Dr. Matt Kulke’s presentation at the New England Carcinoid Connection Patient Conference in June. He presented some interesting information at the conference about where we are in terms of diagnosis and treatment for NET/CS–and did a great job of putting that information into laymen’s terms.

That said, I am increasingly concerned that the science is getting harder and harder to follow–especially for those who are new to NET. I am going to try to change that in the weeks ahead by writing a weekly summary of what I have learned about NET in the preceding seven days. I’ll be trying to put things in terms the average person will understand. But my training is as a journalist not as a doctor and those summaries will be just that: summaries.

I think it is important that we all have a general idea what is going on in the laboratories around the country. But what I write is not intended to be definitive–and I do not intend it to be taken as medical advice. You may raise something with your doctor you read in those pieces but you both need to make medical decisions based on the full research findings, not a layman’s summary intended for a general audience.

Please also remember that promising results in Phase I and Phase II trials are more important to researchers than they are generally to patients. Those studies are done on very small groups of patients. All too frequently those promising early results vanish in the considerably larger Phase III trials.

As I have learned too well from watching my parents whip-sawed by promising early results in Alzheimer’s trials, one should never get too excited about the efficacy of anything new.

We reached a whole lot of people about neuroendocrine tumor cancer and carcinoid syndrome yesterday. The Fall River Herald News ran a story on Walking with Jane’s efforts in raising awareness about NET/CS and our plans to participate in the Jimmy Fund Marathon Walk on September 9.

The piece ran on the front page of the second section of the paper, which has a print circulation of just under 15,000. Given that readership is generally three times the circulation number, about 45,000 people were potentially exposed to our message yesterday.

That does not include the number of online readers. Over 70 people who read the piece online forwarded to their Facebook friends and the like. The piece generated more than 80 hits on our walkingwithjane.org website–about double what we have been averaging this month so far.

The story was also broadcast nationally when the Carcinoid Cancer Foundation picked the story up and distributed it across their network of friends, NET patients and NET researchers.

And now there is a video of me talking about NET and the Marathon Walk. It is pretty stark and my communications students will know everything I did wrong. But…

That makes a small dent in our goal of  reaching three million people about NET/CS this year.

We took another significant step in that direction today. I have just formalized an agreement between Walking with Jane, the Jimmy Fund Marathon Walk, and the Caring for Carcinoid Foundation. Under the agreement, Walking with Jane and CFCF will have a single team: Caring for Carcinoid Walking with Jane. The money raised by that team will all be earmarked for the Walking with Jane Dybowski Fund for Neuroendocrine Cancer. Caring for Carcinoid and the Program in Neuroendocrine and Carcinoid Tumors at Dana-Farber will publicize the team on their sites, as will we.

Now we really need people to take part in the Walk September 9. If you can do all–or part–of the Marathon Walk September 9, please go to the Jimmy Fund Marathon Walk site and sign up for our team. And if you can’t take part in the walk, please make a contribution. No gift is too small or insignificant. Every penny brings us a step closer to a cure.

On Wednesday morning I will meet with Phil Devitt, who heads our press kit group, and Katie Dupere, one of the group’s writers, to talk about other ways to reach people about NET/CS and further publicize the Marathon Walk. We will talk especially about this year’s releases for national media to coincide with NET Cancer Awareness Day on November 10. If you have ideas for stories for that package or contacts that could help get those stories published, please contact us at walkingwithjane@gmail.com.

We are also working on scripts for potential public service announcements and other ways to  get the electronic media involved in telling the NET story to a broader audience.

The good news is we are making some progress. But there is still much to be done. We can’t do it without you.

According to google.com, 110,000 people will do a search for the word carcinoid this month. Another 40,000 will search for neuroendocrine cancer or NET cancer.

When I first typed in carcinoid syndrome and neuroendocrine cancer a little less than two years ago I read everything that was on the web in less than an hour. Most of it was written in thick medical jargon I had too really wrestle with to make sense of. Today, Google sports over 50 pages of information aimed at a wide variety of audiences–from medical students to researchers to doctors to patients to investors and back again.

My problem 23 months ago was too little information. Today, someone coming to the subject likely feels overwhelmed by the stacks of articles and videos available.

I used to try to explain to my students about the rapid pace in the growth of new knowledge. I talked about how little life changed for thousands of years because the pace at which knowledge of the universe increased was so slow. But with the coming of the industrial revolution, everything changed. Both my grandfathers were born in the decade before 1900. There were no radios, no airplanes, no televisions, and, at least where they were living, no cars, trucks or tractors. Both grew up on farms. Nearly everyone did then.

They would both live to see men walk on the moon, the coming of the computer age, electric lights and telephones in every house. My grandmothers lived to see the Internet and the beginnings of the first space station.

I am 60. I was there for the first personal computers–devices so far from what I am typing on right now that it is hard to imagine. I have seen the first heart transplant, the first artificial heart. I have seen many forms of cancer move from death sentence to survival to living with cancer. Had I not lived with it and adapted to it, the changes I have seen would have overwhelmed me. I wonder how I would feel coming to all that information on NET today if I were encountering it for the first time. With the added weight of Jane’s evolving illness, would I have been able to make sense of all that is there?

One of my goals for this website originally was to try to create a place where people new to the disease could find information about the disease without having to wade through Google and Yahoo and Ask and Bing‘s endless reams of seemingly randomly arranged information. The explosion of information that has happened in recent months has not made that task particularly easy–and I am afraid I have not done as good a job of that as I would have liked. Someone once described education reform as building a bicycle while you are trying to ride it. Building Walking with Jane has often felt like a similar task. I keep expecting things to get easier but every day still brings a mountain of new things I have to learn before I can proceed with even the things I learned yesterday.

But I am going to go back to that particular piece of the original vision. Someone needs to be reading these articles and trying to bring more order to them than the “this-had-a-lot-of-readers-and-links” logic of the search engines.

Henry Blake: Rule One is that in war, young men die.

Hawkeye Pierce: So what is Rule Two?

Henry Blake: Doctors can’t change Rule One.

–Quoted from a MASH episode from memory.

I feel a lot like Hawkeye Pierce in that episode tonight. Truth be told, I feel like Hawkeye most days. I am an idealist who is constantly confronted with bitter realities that are often beyond my power to change. That does not mean I stop trying. But it does mean that some days I want to chuck it all and pretend to be dead–as Hawkeye does in another episode.

Last night I went to a benefit concert in New Bedford that raised money for the Devin Laubi Foundation. The group raises money to help young people who have been stricken with cancer and their families. It was formed several years ago after Devin died because his parents saw a need and sought to fill it.

This afternoon I went to a barbecue set up by the family of Susan Borden as a benefit. Susan has days–perhaps hours–to live. She was diagnosed about a year ago with a cancer that has metastasized to her spinal column. I lost an uncle to a similar cancer. I know how excruciating the pain of that can be. And I know too well what it is to watch someone die in that kind of pain. Her daughter is a former editor-in-chief of The Villager–one of a number of young people who have become family to me over the years. Her emotional pain was palpable this afternoon. She had just come from her mother’s bedside.

After the dinner wrapped up I decided it was time to honor a promise I had made to another family who lost a child this year. They asked everyone to have a banana split sometime this summer in memory of their child. I had forgotten the flavors of the traditional banana split and I made sure I savored the taste–not just for that young man and his family–but for Jane as well. She loved ice cream. One of the best parts of any hot summer’s day was when Jane would turn to me and suggest it was time for some ice cream.

Rule One really is that we are all going to die sometime of something. And Rule Two is that we cannot–at least not yet–change Rule One.  But that does not mean we stop trying to save lives. That does not mean that we give up searching for ways to heal wounds and cure diseases. We may have to let the dying go, but it does not mean we have to let them go without putting up a fight.

Go back 500 years and human life expectancies were in the low to mid-40s. Today, life expectancies in the US are close to double that. That does not happen if we just accept the status quo.

So Hawkeye never gives up. Neither will I–though today, I want to.

There is something amazing about long walks that I am not sure anyone who has not taken one can really understand. I did 14 miles this morning in just under four hours as part of my training for the Jimmy Fund Marathon Walk on September 9, and while my legs are tired and–like last weekend–my feet ache a bit, I am amazed at how good I actually feel mentally. The endorphins, while not quite as powerful as after a long run, still leave me with a sense of peace and well-being that is awfully special. The frustrations of yesterday are still there–they just don’t have the edge they had when I started.

I won’t have another really long walk for about three weeks. Next week, even if the workout sheet called for something longish, I would have to pass as I will be running a 5K for Dana-Farber up in Franklin. Running even that 3.1 mile course will put more strain on my legs and lungs than today’s effort. I won’t be running too hard–at 60 the days when I could compete with the young are long gone. But if I can manage a series of 11 minute miles I will be more than happy. The heat and humidity will determine how hard I push myself.

But the next few weeks of the training program call for somewhat shorter walks done at higher speeds before a dress rehearsal in mid-late August. This will make my feet happy, though I have to admit  my brain will miss the thrill of finishing those longer distances.

Periodically, I have to remind myself that everything I do now is more of a Marathon–or an ultra-Marathon–than a sprint. Walking with Jane can only be built one brick at a time or–to keep the metaphor from mixing–one step at a time. We’ve barely been at this 15 months and there is still a ton of stuff to learn–and another ton of stuff to do. At 15 months a baby has just begun to walk and talk. It isn’t ready to debate with Socrates or run the Marathon. At 15 months Walking with Jane is a precocious little thing. We have done three Relays For Life, designed three t-shirts, two bracelets, a water bottle, a button, and a pamphlet, become a corporation with our own checking account, checks and stamp, and become a sought after partner in the fundraising-awareness dance.

And we have some areas of expertise that many start-ups do not have. We know a lot about marketing and public relations. We have people doing art and graphic design who are enormously talented–as are the people who designed this website I get to play on every day. Most importantly, we have a clear vision of what we want to do and a well-conceived plan for how we are going to get there.

Our next two goals are to reach our Relay goal–we are just under $500 short of that–and to get the Marathon Walk project well and truly launched. If you want to help with either of these efforts it is as easy as hitting the link.