Brivanib

Starting to get -- excited isn't quite the word -- but I'm getting something about going down to New York at the end of the week and beginning my pre-screening (CT, blood, EKG) for the brivanib trial. As I've whined to L. more than once, not being in treatment when you know your tumors are growing really stinks.

I had hoped to post something smart about why brivanib might work and how it takes a different angle on things than the drugs I've already had, but somewhere in the haze of VEGFR and FGFR I lost confidence in my ability to figure out what the hell they are talking about and communicate it lucidly. So we'll stick with the basics: Tumors need blood, brivanib hopefully kills the vessels that feed them. This can cause a variety of nasty side effects --including high blood pressure, which I'm already on the verge of struggling with because one of my kidneys is swollen and sending my body all the wrong hormones, but it's all good. I'll deal with whatever I have to deal with when it happens.

In encouraging anecdotal news, I see that Elsa achieved stable disease (retroperitoneal sarcoma) after I believe six weeks on the trial, as did a friend of hers and as did another sarcoma blogger. Michelle of Peace, Love, Cancer describes it this way (I was particularly struck by the "walking zombie" side effect part -- Dr. BT didn't mention that!):

My Scans came back with wonderful results. The Brivanib pills are working! My tumors are stable and haven't grown since my last scan! One tumor in my lymph node has actually died! There is no blood flow to the tumor! This is the best news I could get. My doctor is so happy with these results.

I will be on the pills for 12 weeks. After that I will be given either a Placebo or continue on the pills. Because it is a trial it's a 50, 50 shot that I could get the Placebo. Booooo! I will know right away by how I am feeling. The reaction happens within 15 minutes after I take the pills. I am a walking zombie. If I do get the Placebo, I can then go back on the trial.

A Death. Ghosts. Obligations.

She was a nursing student, pale and slight, swallowed up by her oversized dark green scrubs, but what I remember about her the morning the man died in my hospital room was the way she rushed in to take his hand, and her keening near-shout when he was dead or near it: “You are NOT alone.” 

A lie, but a beautiful one.

I never saw his face. I did hear his voice, and it was gentle and cultivated. You could tell that, as muffled and distorted by the ravages of disease and dementia as it was. When they asked him some questions to assess his mental state, he spoke in a bare whisper, summoning the date, and then, with some struggle, the name of the hospital (though he used a version of it that has been obsolete for 30 years). He said he wanted help later so he could call his son. Then they gave him a little morphine to slow down his heart rate and, instead, the drug stopped his heart. It happened so fast, they couldn’t get me out of the room, so I was privileged enough to witness the end of a life.
*
Not so much recently, but early in the illness, after it became clear how the story was eventually going to end, I would imagine fantasies in which the story did not end, in which part of me remained to watch and help my wife and children as they made their way through life. I couldn’t – can’t – bear to imagine them going through the struggle without me, so I would sometimes catch myself conjuring ghost stories in my day dreams.

But it is the living who must embrace ghosts. From Scientific American Online:

The dead stay with us, that much is clear. They remain in our hearts and minds, of course, but for many people they also linger in our senses—as sights, sounds, smells, touches or presences. Grief hallucinations are a normal reaction to bereavement but are rarely discussed, because people fear they might be considered insane or mentally.

One study, by the researcher Agneta Grimby at the University of Goteborg, found that over 80 percent of elderly people experience hallucinations associated with their dead partner one month after bereavement, as if their perception had yet to catch up with the knowledge of their beloved’s passing. As a marker of how vivid such visions can seem, almost a third of the people reported that they spoke in response to their experiences.

...

Only a minority of people reading this article are likely to experience grief without re-experiencing the dead. We often fall back on the cultural catch all of the “ghost” while the reality is, in many ways, more profound. Our perception is so tuned to their presence that when they are not there to fill that gap, we unconsciously try to mold the world into what we have lived with for so long and so badly long for. Even reality is no match for our love.

*

I often think that is the obligation of living to care for the dying, to keep them warm and rub their feet and moisten their cracked lips, to tell them true and loving things and smooth their passage from this terrible, beautiful world. 

I often think this, but it is wrong, at least in part. It is perhaps more true that we the dying must care for the living; we must ease regrets, soothe hurts, and build bulwarks of memory and love to offer some protection against the terrible, pressing absence ahead.

Emilie

A great friend and teacher I never met died of a sarcoma yesterday holding the hand of her beloved. I will miss you Emilie Lemmons.

*

I have gotten so many things wrong since I became ill, but one thing I got right, I think, was the question. Instead of just asking myself, "When am I going to die?" I have tried to ask, "How do I want to live?"

If you are here because you have been diagnosed with a sarcoma, you could do far worse than read Emilie's brave, eloquent writing to further the work of answering that question for yourself. 

Pensées

My thoughts, arranged in alphabetical order by subject and including daily frequencies (with apologies to Nicholson Baker for shamelessly stealing his joke):

B., life-affirming love of (14 times)
B., annoying and draining nature of (4 times)
Cheese, tastiness of (1.3 times)
Christmas presents, paucity of (6 times)
Christmas presents, bankruptcy-inviting quantity of (4 times)
Death, mine (17 times)
Dogs, glory of (2 times)
Epithelioid sarcoma, treatments and solutions for (6 times)
Epithelioid sarcoma, shittiness and unfairness of (11 times)
Golden Bears, California (4 times)
Homework, hatred of (1 time)
House, disorder of (2 times)
House, beauty and coolness of (3 times)
Job, story of (.6 times)
Lakshmi, Padma (2.1 times)
L. (36 times)
Loss, as fundamental condition of life (12 times)
Marijuana, as possible coping mechanism (1.7 times)
Meaty braised olives, incredible glory of (1 time)
Obama, Barack (4 times)
Shouting (others), unpleasantness of (3 times)
Shouting (own), cathartic nature of (2 times)
T., life-affirming love of (14 times)
T., mystery of how she transformed from beautiful baby into psychotic, infuriating hell-child (5 times)
Tacos, fish (1 time)
Undergarments (women’s), lacy and slinky appeal thereof (1.5 times)
Vicodin, potential administration of (2.5 times)
Wittgenstein, Ludwig (.002 times)

Temperature

L. has always had a soft spot for Jimmy Carter, and I guess I do, too, because I take a great deal of pride in keeping the thermostat low when I'm here in the house by myself. It's true: A sweater, a blanket, a pair of fuzzy socks can work wonders and save big bucks.

But 58, 58 in the warmest core of the house where the thermostat is -- well, 58 is too cold. I am typing to keep myself from shivering. Baby, it's cold inside.

A proposition

A good life is enriched by good tomato sauce.

I've gone through a million different ways of doing it, from a base of diced carrot and onion and a bunch of spices, to a base of onions and garlic and less spices, to ever simpler variations. My current favorite, which distills the sauce down to its very essence, is about as easy as it gets:

Pour a lot (a quarter-cup, say) of olive oil into a saucepan and begin warming it over medium-low eat. Peel and bruise (with the flat of a knife) three garlic gloves. Place them in the oil and let them simmer, warm and infuse. Get a big can of San Marzano or Muir Glen whole tomatoes, and tear them up with your hands and place them in the pot. Dump in the juice, too. Add a big hit of salt (this is crucial). Raise the heat a bit until you hit a boil, then back it off until you're at a decent simmer. Let it concentrate and reduce until it no longer looks quite so liquidy -- maybe a half hour so? Finish with a glug more of olive oil, salt and pepper as you like them, and maybe red pepper flakes if the sauce is over-reduced and sweeter than you prefer. (A little red wine or a tiny bit of vinegar can also help you achieve balance.) Fish out the cloves, then serve.

Variation 1: Cook about a quarter-pound of pancetta in olive oil in medium heat until it crisps up a bit and renders its fat. Remove it from the pot. Add a chopped shallot or two (or half a yellow onion) and cook until it softens. Proceed as above, perhaps with slightly less olive oil since you have the pancetta fat. Finish as above, adding back in the pancetta and a good hit of red pepper flakes. Serve with penne.

Variation 2: Reduce the sauce with a few basil leaves in it (fish them out before you serve) for extra perfume.

Bonus cooking-mojo tip: This recipe dresses a pound of pasta adequately. Remember, you don't want your pasta swimming in sauce. If the sauce is too thick, you can thin it out a little by nabbing some of the starchy pasta-cooking water from the pot and stirring it in. This supposedly helps the sauce and pasta harmonize.

Survivor

Insert your own Rocky/"Eye of the Tiger" joke here. I was going to, but, as it turns out, I got nothing.

Just a word. Below, I described Josh as a fellow "epithelioid sarcoma survivor." Writing that felt a little weird, actually -- I am sorry to say that adjectives like "sufferer" or "victim" make more emotional sense to me personally, but I didn't want to characterize another person's experience.

The truth is that a lot of cancer survivor culture pisses me off. I mean, I'm really glad if you've beaten cancer, and I can imagine the lingering dread, but I just can't feel too much of your pain; I only wish for a big hit of survivor angst. If that's a problem, give me problems.

A wise person I know, though, described a cancer survivor as anyone who is living with the disease. You don't have to have clear scans for X months or a great prognosis or whatever. I love the note of defiance and hard truth in that formulation, and I think I am going to strive to feel it. I'm a survivor.

Why didn't I think of that

via Boing Boing, city workers in Ankeny, Iowa are spreading garlic salt (a local factory donated 18,000 pounds) on roads to help melt the ice. From the AP:

Olson says the city mixed the garlic salt with regular road salt and it works fine. He says some road workers say it makes them hungry...

An assignment of sorts

Inspired by fellow epithelioid sarcoma survivor and all-around interesting guy Josh, I spent a few hours the other day drafting an "ethical will" for B. and T. The idea is to write a document that serves as a kind of inheritance for your loved ones -- but an inheritance of ideas and values rather than material possessions. 

Ethicalwill.com describes them as a sort of love letter to your family; a way "to share your values, blessings, life's lessons, hopes and dreams for the future, love, and forgiveness with your family, friends, and community." There's no set format, and the examples on the site are all over the map, so I spent some time sharing with T. and B. some of my thoughts and observations about life. 

I thought it might be weird, but it wasn't. Although I produced an initial flurry of letters and thoughts for L. and the kids immediately after I got sick, I have been far more reticent lately. As I got sicker and more worn down from treatments, I became less willing to voluntarily grapple with my death in that way. Silly, I know; but it's how I have felt. Drafting the will turned out to be fun and intensely meaningful, however. It didn't feel morbid, perhaps because I have a promising treatment ahead and am feeling OK-ish physically.

So here's my suggested assignment to you, my readers, both the sick and the well: Sometime before the end of the year, write a letter to someone you love sharing things you wish to share with them. (L. used to write an annual Christmas letter to B., which was a wonderful idea.) Hopefully and probably no one will read it for decades -- though I don't see any reason why you couldn't share it at the right time while everyone is still around. Don't get all Flaubert about it. Commit to sitting in front of the computer for 15 minutes. Sit there and write the first sentence. Then write the second and the third. It doesn't have to be perfect. You can say anything. You can write another letter to amplify the first, so don't think you have to get it all down perfectly in the first shot. Just write something. It matters. 

I'm actually a little worried that my document reads like a unfortunate cross between All I Really Need to Know I Learned in Kindergarten and Life's Little Instruction Manual, but approaching the writing in a somewhat light way was the trick I needed to help me say some of the heavy things that I wanted to say. Anyway, here's a little snippet of what I came up with. Maybe it will trigger something in you:

MATTERS DEVELOPMENTAL

I like to think of myself as a pretty good person, reasonably well-adapted and happy, but you’ll have to trust me that much of my early life was a train wreck.

...

I myself acted out horribly in school for years, causing many unnecessary problems for myself and others.

I was a terrible nerd. Fat, carbuncular, possessed of awkward clothing and demeanor, consumed at times by despair and solipsism.

But I grew out of it, you know. And even at my unhappiest and least attractive, I was reading, thinking and engaging with my (very few, but high quality) friends.

Change can happen so suddenly. I started ninth grade, and everything was different. Over the course of less than a year, I shot up about a foot, going from pudgy to slender, bought new clothes and adopted a new hair style, traded my glasses for contact lenses, got my braces taken off, etc. These external issues didn’t fix my problems, but they did relieve them. Skateboarding helped, too. Remember that the eccentricities and interests that make you geeky in school, especially junior high school, often prove to be highly adaptive in adult life.

Yes, transience. Even now when I am facing the terrible prospect of losing my beloved wife and two beautiful children to a horrible, painful, humiliating, creeping disease, I still find that the most visceral despair I have ever felt I felt in my adolescence and teenage years. Seriously. Heed that for a second: I am honestly telling you that growing up is harder than having cancer. Heed this as well, it’s even more important: Many of the problems I suffered the most over simply did not matter. I don’t even remember what they are now. Repeat to yourself over and over that this too shall pass. I hope that I am not making light of how difficult this time of life is – remember, my guts shrink even now thinking of the many and varied agonies of junior high and after – but time and perspective are crucial friends.

Your mom knows more than you think. But she makes mistakes, also. Forgive her and love her. Fate cheated you out of your dad; don’t cheat yourself out of your mom.

Value family. It has sustained me my entire life; first my parents, then your mother and you two.

I am so sorry I have to leave the two of you. I love you so much; I fight and fight and fight to live to be with our family.

You are eventually going to be fine, I swear it. I know you both, my little darlings.

Annals of theology

A Christmas story of sorts:

Little T. and I are sitting on the floor of her room, spinning out elaborate pretend-play scenarios, when she suddenly looks up and sees the fairy costume hanging in her closet.

"Look, it's a fairy princess of God!"

"A fairy princess of God? Is that like a regular fairy princess, or is it a special kind?"

"It's a special kind!"

"What is God, anyway?"

"It's where Jesus lives! And you know that! From your logical studies!"

'A randomized discontinuation study'

I'll admit it: I felt a little smarter just typing that. I mentioned (threatened?) earlier that I wanted to say a little bit about the brivanib protocol, because it strikes me as interesting and somewhat unusual. I barely have any experience at all with clinical trials, and I've already learned an obvious yet somehow counter-intuitive point: The trials aren't designed to help you. They are designed to bring safe, effective drugs to market as quickly as possible. If they help you, that's great, but it's not the primary goal.

Anyway, the study works like this: You get the drug for sure for 12 weeks. If your tumor grows, you're out of the study. If your tumor shrinks more than 20 percent or so, you stay on the drug for sure. If your tumor remains essentially the same size, you are randomized into a double blind, placebo-controlled group. You may get the drug, you may get the placebo (ugh). If your tumor grows, they unblind the study to find out whether you are receiving brivanib or placebo. If your tumor grew on the placebo but was stable on the drug, they will switch you back to the drug. The protocol requires scans every six weeks, so it looks to me like the time off-drug could be relatively short.

My wicked, wicked ways

Two examples:

1) Toys 'R Us gives me hives and yet... every time I try to get out, they pull me right back in. I made my way over there yesterday in the hopes of filling in a last couple Christmas presents and saw a car with several bumper stickers espousing views I find despicable. Apparently intending to shame an inanimate object for carrying perfectly mainstream political messages, I decide to raise my middle finger at the bumper. The lot is crawling with toddlers. I sheepishly furl the finger and slowly make my way into the crowded, denuded store through the vestibule that always smells like stale cigarette smoke.

2) I'm making dinner, and T. is hungry. She expresses this by saying "I'm hungry I'm hungry I AM HUNGRY I'm Hungry I'm Hungry I'm Hungry I AM hungry Hungry..." The only thing missing from the prison riot was the tattoo of tin cups being banged against bars. I'm trying to finish the cooking as my blood pressure is redlining, and finally I throw some food on a plate and say, "Ok, T., it's ready. Come to the table [undertone] you little jerk." Later, of course, both children were so unbelievably cute and charming that my heart split open.

ES in the news...

Google Alerts turned up a rare new mention of epithelioid sarcoma in a University of Michigan press release:

One day Gisele Bigras was a college student finishing up another year of school. The next day, she was a cancer patient faced with having one of her fingers removed.

The diagnosis: epithelioid sarcoma in her middle finger. Bigras, 19, was in a state of shock and panic. But music brought her back.

"Music has always played a huge part in my life. Music therapy helped me focus on something else other than the traumatic events of the cancer diagnosis, and just forget for an hour or so, to just go into a different world for a little bit," Bigras says.

Get well, Gisele.

Back from NY

We went down to New York at the end of the last week to consult with Dr. Bow Tie (red for this visit, and askew) about clinical trials at Sloan-Kettering. 

The options we were offered were the brivanib trial (an oral anti-angiogenesis drug) and a phase I of an mTOR inhibitor (everolimus) combined with cisplatin. It turned out that the phase I was filled -- so brivanib, here we come. 

We need to fight with the insurance company -- unlike Ariad, the drug company for this one is not footing the bills for doctor visits and scans -- and do a bunch of screening tests. I'll be in New York again on January 2, and will continue with weekly visits for about six weeks. After that the visits will be every three weeks. The brivanib trial has a pretty wild protocol that allows for a placebo control while minimizing or eliminating time spent off-drug if the agent is helping. Alas, I'm too tired to get into that right now, so you'll have to wait for the next exciting edition. The trips will be expensive and, probably, difficult, but being in New York City weekly is sort of a dream come true for me, so I'm trying to emphasize that part of it and ignore the fatigue and money. 

Amusing, semi-classic Dr. BT moment from the trip: He and his fellow were apparently eyeing my lungs with some concern and disbelief, so he ran upstairs to consult with a thoracic surgeon. I have my issues with Sloan, but the multi-disciplinary teams and intense specialization of the people there is one of the cool aspects of the place. Anyway, he comes down and says the guy thinks a chest tube might be worth a shot, and maybe VATS on the left side if the tube can bring the lung up successfully. We then have this exchange, abbreviated only slightly:

"He has concerns about you flying."

"I admit that it's occurred to me that I might throw a PE or something."

"No, no: It's the pressure differential. How did you get down here?"

"Uh... I flew. Should I be concerned?"

"Well, you have to get home."

*

As always in NY, there was some room for joy. We ate here, like always, and nearly missed our flight (despite arriving at the airport two hours early) because of an ordering mishap at the new tapas bar that led to us receive one-and-a-half liters of sangria rather than a half liter. You know, we couldn't waste it. So L. and I ended up charging off together, hand-in-hand and half-stumbling, to the closed gate. 

It's kind of cool that I can stare my mortality in the face for two years, survive an untold number of physical and emotional traumas, and still manage to be the same immature jackass I've always been. That's talent.

*

Bonus post segment: The wit and wisdom of a naughty boy (part one of a five-part series): 

"B., are there any new clothes you'd like for Christmas?" 

"Yes: a tuxedo!"

The wit and wisdom of a naughty girl (part 2 of a 586-part series)

Me: "Oh, T., you're such a wonderful girl!"

Her: "That's an urban legend." (She seriously said this. She's four.)

Department of Awkward Conversations

Things I've never quite had the nerve to say when the wrong person asks me, "So... how are you doing?":

I'm rocking, except for the fact that my body is collapsing all around me.

Cancer is a great teacher. I now understand the impulse behind suicide AND infanticide. 

[Spoken with a demented grin:] Great! [Also: "Peachy!" "Fab!" "Grand!" "Super!"]

Ah, you know, it's Wednesday -- humped back day.

Not bad for a metastasis Monday...

How about those Raiders?

Something difficult I wish I had said more the many times when it was true:

Kind of terrible, but thank you so much for asking.

What I would say right now if someone popped the question:

Kind of terrible, but thank you so much for asking.

Live weakly (the sequel)

So I'm schlumping through the grocery store this morning after a marathon doctor appointment hoping to fill some prescriptions and buy some macaroni and cheese, and I find that the pharmacy is backed up an hour or more so I won't get my scripts, and the mac and cheese is not in the spiffy organic section, nor is it in the conventional section... the Annie's now lives on aisle one, which just happens to be on the opposite side of the store. I limp back over, rueing this massive conspiracy designed to thwart and annoy me -- me, me, me! And don't even get me started on the high-priced organic coffee filters I saw: The brand name was "If You Care" (emblazoned on classily understated packaging in a lovely, Earth-friendly type treatment), and they were woven from the flaxen hair of vegan maidens or something. My thought was: No, I don't care. I DON'T care about your stupid, high-virtue coffee filters. I have cancer; piss off.

*

All this ranting is by way of introducing a resonant post from Emilie, who starts talking about cancer and strength from the launching point of a book she's meaning to read, Cancer Made Me a Shallower Person. Although this is an ongoing concern of mine -- see this post reacting to another person's smart thoughts about "living weakly" -- I can't really expand on what Emilie has to say right now, so follow the link over to her place. One little thought, though: Part of the reason I am trying lately to talk about hard things like diapers is that I believe that there is a kind of strength-in-weakness; that is, strength in letting yourself see and feel fully as many dimensions of this experience as possible, as hard and as painful as that may be. 

Once more with feeling

In the aftermath of the test, I've had the thought a couple of times that, weirdly, I have already had almost this exact bad news -- a tumorous lymph node is messing with my left kidney, some other nodes on the retroperitoneal chain are growing but not huge, and there's mysterious crud on my lungs -- before. (It was earlier this year when "gem/tax the sequel" bombed at the box office.) 

And yet... it doesn't get any easier. Whether it's the whole post-hospital PTSD thing, a grinding away of my coping mechanisms, or something else, the tests, procedures and bad news are getting harder and harder to take. And this for some reason makes me think of Malcolm Gladwell and his thoughts on practice:

This idea - that excellence at a complex task requires a critical, minimum level of practice - surfaces again and again in studies of expertise. In fact, researchers have settled on what they believe is a magic number for true expertise: 10,000 hours.

"In study after study, of composers, basketball players, fiction writers, ice-skaters, concert pianists, chess players, master criminals," writes the neurologist Daniel Levitin, "this number comes up again and again. Ten thousand hours is equivalent to roughly three hours a day, or 20 hours a week, of practice over 10 years... No one has yet found a case in which true world-class expertise was accomplished in less time. It seems that it takes the brain this long to assimilate all that it needs to know to achieve true mastery."

No wonder it's so hard. I'm a piker! A neophyte! Another 9,983 hours or so and I'll handle the bad news and those long waits in the doctor's office like a champ....

Bad news

It's been crummy around here lately, first freezing and then oozing trickles of rain. So I was jolted this morning when, on the way home from the hospital, a fat, billowy cumulus shifted its relation to the sun and the sky turned electric blue and suddenly everything was bathed in that sharp winter light that heightens the contrast of things. It would have felt like a portent of something, except my CT scan showed progression of my tumors and I have now left the deforolimus study.

I was given a "wet read" -- my doctor looked at the pictures herself, either without the radiologist or only with a quick, informal consult. The news could have been worse; there was no obvious major spread of disease and my lungs look the same as before. But a lymph node crowded against a vein that feeds my left kidney has grown significantly, and the kidney itself has swollen in protest. Some lymph nodes lower on the chain, this time in my lower back, have also grown. So now we move on to the next thing: Consulting with Sloan-Kettering, and beginning another trial or treatment as soon as possible.

I may have a little more to say about this once I've had a time to process what has happened and I receive a formal report of the CT findings.

Laughing and crying

Warning, the following contains too much information.

So my stomach has been screwed up in various ways for two weeks or so now, and it's gotten really bad the last few days. Heading into my CT, I was worried about this because even under the best of circumstances, drinking two liters of banana-flavored barium contrast solution screws up my stomach. There is no worse feeling than being trapped inside the machine, or even stuck way up on the table, and having to throw up or go to the bathroom. So I wanted to let the techs know where I was at: "Sorry to lay this on you, but stomach is feeling really queasy and I've been having a lot of diarrhea, so I just want to make sure that everyone is prepared for what might happen and we can make any necessary cleanup as non-traumatic for all of us as possible."

They laid some special stuff on the table, got me a little basin in case I needed to throw up, and set up the IV. By that time, my stomach was clutched in knots and I took a last trip to the bathroom. When I came out, the nurse somewhat shyly offered me a diaper. But not just any diaper. This thing was fit for an offensive tackle or a morbidly obese fortune teller. Folded up, it was about the size of a baby blanket. As I put it on, I had a sudden vivid memory of when the kids were infants, and how when they moved up to the next size of diapers during that time, the new diapers always seemed so huge... I flashed on a memory of those little distended infant belly buttons, with the adhesive tabs on either side of the diaper almost meeting in the middle. I laughed hard as I stuffed the monstrosity into my pants and went up on the table.

I'm thinking that most of you probably haven't worn a diaper in recent memory. It sucks, obviously. You don't feel sexy. But I vowed at the start of this whole thing that I would not feel ashamed of my body. I haven't lived up to that perfectly, not even close, but a diaper (even one the size of a mainsail) is nothing in the scheme of things. And it still makes me chuckle, particularly because I didn't end up needing it. Even though I have probably said it dozens of times, I've always hated the expression "If I don't laugh, I'd cry" because you need to laugh and cry; both in illness, and in regular life. 

I'm laughing now, a little, and soon I will cry.

One of the greatest headlines ever written

Study Suggests Cancers May Go Away on Their Own

Isn't it pretty to think so?

Encouraging news on Temodar

A new study finds decent news for Temodar with unresectable and metastatic leiomyosarcoma. Although one can't simply extrapolate results from one sarcoma subtype to another, I thought this was worth mentioning because I found very little encouraging news about Temodar/temozolomide for sarcoma earlier this year. (I eventually took the drug anyway and had stable disease for four months or so, which qualified me for the deforolimus trial.)

The protocol used thalidomide as well, but the investigators believe that the temozolomide was the active agent. A quarter of the patients achieved stable disease for at least six months, which I count as a significant achievement given that these folks were pretty sick.

The abstract:

We assessed the efficacy of combined temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma in a phase II single-institution trial. Twenty-four patients were enrolled. Temozolomide (150 mg/m2/day for 7 days every other week) was administered with concomitant thalidomide (200 mg/day), and continued until unacceptable toxicity or disease progression. There were no complete responses and two (10%) partial responses. Five patients (24%) had stable disease for at least six months. Fourteen patients (67%) progressed after a median of two-month treatment. The median overall survival (twenty-two assessable patients) was 9.5 months [95% CI 7–28 months]. There were no treatment-related deaths or CTC grade 4 toxicities. Thirteen patients were dose-reduced or discontinued thalidomide due to toxicity. In conclusion, this combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with advanced leiomyosarcoma. We hypothesize that temozolomide is the active agent in this regimen, and should be further studied.

The wit and wisdom of a naughty girl (part 1 of a 586-part series)

Some things my daughter has said recently:

A Jacuzzi. [In response to a question about what she’d like for Christmas.]
A swimming pool then! [In response to the suggestion that a Jacuzzi might be too large for Santa’s sleigh.]
It’s not tight! I just need to stretch it out a little!
You know what I’m not paying attention to? YOU!

*

By the way, I don't mean "naughty" pejoratively. Though she drives us crazy at times -- dealing with her willful behavior and tantrums can be exhausting -- her spirit is amazing and will, I think, serve her well in life.

Checking in

Nothing much to report, but I wanted to check everyone in on the trial and how I'm feeling. 

It's a little ridiculous, but I've been reticent about talking about my symptoms because of the possibility that I'm receiving a placebo instead of actual medicine. I'd hate to chronicle every daily up and down here and then yank the rug out at some future point. I've also learned not to trust many of my reactions to my own body -- every sensation can seem like a symptom, and my baseline level of wellness isn't terrific. This makes it very difficult for me to say what's going on.

That said, I'm starting to feel like I may be getting the drug. The first three-to-four weeks of the trial were quiet; I felt nothing, basically. Then, almost two weeks ago, a tiny little bump popped up in my mouth, quickly followed by a few more. They didn't ulcerate as miserably as mouth sores usually do, but I was encouraged anyway. I also started to feel even more tired and to have some difficulties with my stomach (nausea, lack of appetite, etc.). The big test will come Nov. 26, when I have my first set of bimonthly scans for this trial.

By the way, Elsa is describing her experiences with the brivanib trial at Sloan-Kettering at her fine blog, Living With A Sarcoma. I'm following this closely, because it is an option that I may pursue at some point.

The cancer genome

Although there are no immediate implications for cancer treatment, I highly recommend this New York Times article on a groundbreaking new study. The scientists essentially created a personal genome for a person with cancer, then compared the DNA in cancer cells with the DNA in healthy cells to lock in on the mutations associated with the disease. The work is fascinating.

Some of the patient’s mutated genes appeared to promote cancer growth. One probably made the cancer drug-resistant by enabling the tumor cells to pump chemotherapy drugs right out of the cell before they could do their work. The other mutated genes seemed to be tumor suppressors, the body’s natural defense against dangerous genetic mistakes.

“Their job is surveillance,” Dr. Wilson said. “If cells start to do something out of control, these genes are there to shut it down. When we find three or four suppressors inactivated, it’s almost like tumor has systematically started to knock out that surveillance mechanism. That makes it tougher to kill. It gets a little freaky. This is unscientific, but we say, gee, it looks like the tumor has a mind of its own, it knows what genes it has to take out to be successful. It’s amazing.”

Writing lessons from Barack Obama

I was struck last night, and again today, by the quality of Barack Obama's brief speech at Grant Park. I was impressed by its disciplined eloquence and found some lessons for my own writing within its construction.

1) Get right into it. Political speeches (and articles and blog posts and bad short stories and...) often start with ritualistic throat-clearings thank-you's to the Jefferson County Rotarians. Not Obama's. He greeted the crowd, then launched in:

If there is anyone out there who still doubts that America is a place where all things are possible; who still wonders if the dream of our founders is alive in our time; who still questions the power of our democracy, tonight is your answer.

2) Make it new. We all know that Obama's election was "historic." The TV commentators reminded us every half second. But what does that mean? Obama took an abstraction vitiated by overuse and made it real by telling the story of Ann Nixon Cooper, a 106-year-old woman whose adoptive mother was a slave. This, granted, is the same impulse that gave us Joe the Plumber and every grating "real person" at a state of the union speech, but look what Obama does with it:

This election had many firsts and many stories that will be told for generations. But one that's on my mind tonight is about a woman who cast her ballot in Atlanta. She's a lot like the millions of others who stood in line to make their voice heard in this election except for one thing -- Ann Nixon Cooper is 106 years old.

She was born just a generation past slavery; a time when there were no cars on the road or planes in the sky; when someone like her couldn't vote for two reasons - because she was a woman and because of the color of her skin.

3) Complete the circle(s). The climax of the speech is set up by Ann Nixon Cooper. Obama uses her life to frame the last century of American history and to recapitulate one of his campaign slogans. Returning so strongly to the "Yes we can" of the primaries rhetorically completes the transition from candidate to president. But Obama is working a variation of his theme, not repeating it. Last night, "Yes we can" was less a rallying cry than a promise. The shift suited the moment: exhilaration intermingled with the sobering knowledge of the work ahead. 

And tonight, I think about all that she's seen throughout her century in America -- the heartache and the hope; the struggle and the progress; the times we were told that we can't, and the people who pressed on with that American creed: Yes we can.

At a time when women's voices were silenced and their hopes dismissed, she lived to see them stand up and speak out and reach for the ballot. Yes we can.

When there was despair in the dust bowl and depression across the land, she saw a nation conquer fear itself with a New Deal, new jobs and a new sense of common purpose. Yes we can.

When the bombs fell on our harbor and tyranny threatened the world, she was there to witness a generation rise to greatness and a democracy was saved. Yes we can.

She was there for the buses in Montgomery, the hoses in Birmingham, a bridge in Selma, and a preacher from Atlanta who told a people that "We Shall Overcome." Yes we can.

A man touched down on the moon, a wall came down in Berlin, a world was connected by our own science and imagination. And this year, in this election, she touched her finger to a screen, and cast her vote, because after 106 years in America, through the best of times and the darkest of hours, she knows how America can change. Yes we can.

Most of us would have been satisfied to close with this new, rounder version of one of our earliest political rallying cries, in the same way that lots of journalists end a story by recapping or extending the story's beginning in some way. But Obama has another move in him, one that works rhetorically and substantively. He turns from Cooper and our past to his daughters and the future:

America, we have come so far. We have seen so much. But there is so much more to do. So tonight, let us ask ourselves -- if our children should live to see the next century; if my daughters should be so lucky to live as long as Ann Nixon Cooper, what change will they see? What progress will we have made?

This is our chance to answer that call. This is our moment. This is our time...

Of pens and patients

Harold J. Wilson would make fun of my banality, but I'm continually amazed by how impersonal medicine is. And it's not like I'm expecting a B&B with chintz and ricotta pancakes. Josh (get well and get that sunscreen, buddy) offers a good rundown of the procedure experience here:

Another waiting room. 

Another long wait.
Another day fasting.
Another nurse with another medical history survey and a list of the same questions as I lay on a pre-op bed.
Another chance to teach a medical intern our history.
Another poke with a needle for another blood draw and IV.
Another time saying goodbye to Kim before going into another cold operating room.
Another set of vitals appearing on a monitor then shifting from one bed to the operating table, more faceless people behind surgical masks and doctors I don’t meet.

...

The patient's experience immediately before a procedure is an odd combination of being the center of attention and yet feeling almost completely irrelevant. (Is this how John McCain feels when he appears at a rally with Sarah Palin?) There are folks milling around chatting with each other and setting up the equipment, but usually only one of them is, at any given time, actually paying attention to you. As Josh points out, you sometimes find out who some of these people are only when you get the explanation of benefits from the insurance company. Weird stuff. Even weirder: Before one little ditty at Sloan-Kettering, my doctor was holed up in a corner feverishly checking his e-mail until about a millisecond before the anesthesiologist knocked me out.

For some reason, thinking about the ways that medicine can feel crude and inhuman made me think of pens -- specifically, ball point pens and Sharpies. It's often good practice for a doctor to write on a patient's body -- "amputate here," "x marks the spot," whatever -- and to do so, they typically use a regular pen. I would have thought there would be some special super-duper medical marking pen (and, in fact, there are), but the only thing anyone has ever written on me with was a Sharpie. 

Except once. 

When I was getting a lymph node biopsy, the guy doing the procedure (an inexperienced specialist your hospital gives gravitas to with the title "fellow") was having a lot of trouble finding the nodes with his ultrasound, so the big dog doc ambled in to set him straight. When he homed in, he reached into his pocket and pulled out a ball-point pen to mark their location and the needle insertion angle at one of the tenderest points of my inner thighs. Two observations: 1) A ball point pen doesn't write very well on flesh. Takes a lot of pressure; 2) The distinguishing feature of such a pen, as denoted by its name, is point.  As little T. would say, "Owwie."

I thought of this after reading this story investigating the possibility of germ transmission by hospital Sharpie pens. It turns out that they do not hold bacteria while the fancy, medical-specific pens do (both are supposed to be discarded after one use anyway). Score one for crudity, I guess. Maybe even score two: One sad aspect of the biopsy story just occurred to me. Even though I resented the oblivious scratchings of the ball-point-toting big doc, after 45 or more stressful minutes on the table while the young dude futzed around, I was pathetically grateful for his decisiveness.

Morning, noon, night

Morbid brother that I am, this TNR book review caught my eye. 

'To philosophize is to learn to die": seven words, and an epoch in Western thought. According to Plato in the Phaedo, one of the inextinguishable monuments that he erected to his martyred teacher, Socrates believed that philosophy was a way of "practicing dying." Cicero, who set himself the task of making philosophy speak Latin, translated "practice" not with meditatio but commentatio--meaning "careful preparation," from which we get our own "commentary" or "study." Study, he implies, takes us outside ourselves, beyond our bodily needs, and thus helps us to transcend our physical finitude.

Yet there is also, in Cicero's momentous linguistic decision, the implication that what one studies, as well as that one studies, prepares us while alive to meet our eventual fate. Philosophy can teach endurance, forbearance, and perspective amid both joy and catastrophe. Those who live in fear of death also live in fear of pain, in fear of danger, in fear of the new; but those who accept the reality of death are freed from all these fetters.

I can't comment on the substance and conclusions of the piece -- I'm only about a third of the way in, though I'm enjoying it so far -- but I did want to say something about a comment appended to it that I've been chuckling about for the last hour or so. In the finest Internet tradition, a Smart Guy Explains It All To Us:

Does not Professor Miller [author of the review] understand the basic truth that living and dying are part of each other? The banality of his conclusion amazes me. To live well must include dying; to die well includes the appropriate conclusion to a meaningful life. What is mysterious about that?

Thank you, Harold J. Wilson, sage of the age. Now, this piece may well ultimately come to a banal conclusion -- and Wilson's comment, clearly, is more right than wrong in its substance. But sweet Jesus, what that "basic truth" of the unity of death and life elides. At risk of making another banal conclusion, let me quote the old saw that there's knowing, and there's knowing. How to make leap between the two -- with faith, with reason, with any means available to you -- now that's a freakin' mystery.

I'm with Reagan

It's frivolous, but I can't resist linking to this first-person piece about mixing politics with medicine. Although I've occasionally enjoyed joking with nurses about things like the Fox News howling in the background in the hellish radiology waiting room, I'd just as soon not know how most of these folks feel about the issues of the day (except, possibly, in terms of health care). 

An excerpt:

Remember when Ronald Reagan was shot in 1981? He quipped to the doctor who was going to operate on him, "I hope you're a Republican." The doctor replied, "Today, Mr. President, we're all Republicans." That would have been less convincing from someone wearing a Carter-Mondale pin.

Reading

There isn't a lot of actionable information, but the Los Angeles Times Health Section is currently offering a large package of cancer-related articles. Two that were particularly interesting to me were For Cancer Patients, Personalized Treatment Offers A New Range Of Options -- and Hope and The Quest for Cancer-Preventing Drugs.

What's going on?

Perhaps a side effect of deforolimus (or placebo) is some sort of inhibitory effect on blogging?

Sorry for the radio silence here, but shortly after starting the trial I got hellaciously sick. At first I hoped the fevers were something akin to the mysterious fevers that struck me 48-72 hours after receiving Gemzar, but it turns out they were probably just an infection. Anyway, I seem to have finally shaken it off, so I'll try to start posting more frequently here.

I haven't noticed anything that feels like a new side effect of the drug, alas. I'll see the doctor and have more bloodwork done in about a week, which might offer a clue as to what's going on. I'm also right in the midst of the expected wheelhouse for developing the mouth sores. If I find any, I'll surely post -- because what more fascinating topic of conversation is there than mouth sores? 

Viva Placebo!

via Ezra Klein, I thought these charts on the efficacy of placebo treatments for three diverse disorders were interesting....

In search of side effects

I'm currently in the odd position of ardently hoping for chemo-related side-effects. 

I want to know whether I'm taking deforolimus or the placebo, and the way I'm going to find out (*) is by monitoring my blood work and symptoms closely. But through some weird sort of medical certainty principle (Schrödoctor's?), obsessively monitoring one's body for symptoms... ensures that you'll experience symptoms. In the kind of sterling move that probably would have been smart before I started this trial, I searched for deforolimus side effects and found this article from a patient advocacy organization recounting a presentation by Camille Bedosian, Ariad's chief medical officer. This was a year or so ago, but the non-legally-vetted talk is more illuminating than Ariad's official publications.

Some excerpts:

Why would someone who has had a favorable response to chemo want to take deforolimus? 

People who have gotten remission are unlikely to stay on chemo, but they may want to take deforolimus in hopes of staving off a recurrence. Also, it is common for people on chemo to take a break from time to time to let their body recover a bit. Those who have had shrinkage or stability may want to take deforolimus while on a break from chemo. Others may have reached their limit of a certain kind of chemo or be waiting to figure out what to do next.

...  
Even so, why test the drug against a placebo?

"How are we going to know if it works?" Dr. Bedrosian said. Dr. Sant Chawla of Los Angeles added, "Someone has to prove this to the nonbelievers. Otherwise, we’ll be talking about this for 10 years."

If people get new tumors or their existing tumors grow, they have to leave the trial. Those who were on the placebo can't get the drug, Dr. Bedrosian said, because that would affect the trial results. People who complete the trial will be told whether they got the drug or the placebo. If they got the placebo, they will not be allowed to get the drug.

If people get side effects, won't they know they are getting the drug, not the placebo? For example, she said, about 70 percent of the people who took deforolimus before have gotten mouth sores.

But some of these sores were minor – similar to what people get in the general population, she said. People who have had chemo recently may have a hard time distinguishing chemo side effects from the side effects of deforolimus.

Bedosian also mentioned that they felt like deforolimus worked best against faster-growing sarcomas and that about one-third of heavily pre-treated patients in phase II trials had a positive response to the drug. I summarized some information about the study design and side effects here. 

According to my doctor, the mouth sores (a 70 percent side effect, according to Bedosian) can often be resolved by temporarily altering the dosing scheme; they won't necessarily last the entire course of treatment. 

And so here I find myself, searching for mouth sores, and wondering if the stomach ache I had last night is related to my flu shot, the pepperoni pizza I ate, the chemotherapy, or the anxiety of living with still more uncertainty. 

---

* Ariad is willing to "break the code" if necessary once you leave the study and tell you whether you received the drug or the placebo. I would like to know sooner, however.

And so it begins

The weirdness struck me an hour or so into the appointment, when I was told, "We've called Ariad. They are randomizing you right now." I considered praying, but it felt false. I hoped instead. A number was generated, and the hospital staff pulled the appropriate package from the pharmacy. One contained medicine, the other sugar. We wrestled the tiny pills out of their foil, I took four, and we waited an hour while I was kept under observation. Then it was home. I sat on the sofa, exhausted and a bit bewildered by what had just occurred.

37!

The sad truth is that I probably would have felt bad about turning 37 a few years ago. It would have sounded old to me; a nose too close to 40. I would have felt bad about the books I haven't written, the careers I haven't pursued, the wide recognition I haven't gotten.

Now, of course, 37 seems heartbreakingly young, and my birthday is, once again, a source of joy rather than melancholy. I spent both 35 and 36 in the hospital -- with last year's jaunt to the ICU being particularly horrible -- so I was so grateful to have cake at home with my family. It was a quiet night, but 40 -- 40's gonna be a party. Save the date.

God and whiskey

I pretty much hated this piece, but I have to admit that the lede got my attention:

I looked death in the face. All right, I didn't. I glimpsed him in a crowd. I've been diagnosed with cancer, of a very treatable kind. I'm told I have a 95% chance of survival. Come to think of it -- as a drinking, smoking, saturated-fat hound -- my chance of survival has been improved by cancer

.

The son

One of the second-grade girls got a little frisky with B. yesterday, kissing and hugging him to his professed consternation. 

It brought back memories of the time in kindergarten when Big Tina chased me down like a lion pursuing a sick wildebeest, planting a couple of smackers on my cheeks while I secretly wished that little Tina, the redhead, had done the chasing and the kissing.

We discussed ways to dissuade this behavior. B.'s first instinct was that his fists might be helpful, but I pushed for a softer-line solution. "She's your friend, B.," I said, "and she's hugging you because she likes you. You don't want to hurt or scare one of your friends. It's OK to say that you don't want her to touch you, but if you freak out she'll just want to do it more."

He considered this, and replied. "The school regulations" -- love that word choice, "regulations" -- "say that kissing is never OK, and that hugging is only OK if the person asks first. I didn't ask first!"

Later, at soccer practice, the little girl chanted "B.'s here! B.'s here!" when we showed up and, in fact, snuck in a little kiss in line. B. didn't look too upset.

*

On the way home, we talked about the cancer a little bit.

"Dad, I'm sort of glad that you're sick because we get to spend more time together. I mean, I'm not glad, but..." We went on from there, him breaking my heart with every word. On the one hand, he loves computer games and war books and thinks it might be a good idea to whack a cute little girl for hugging him. On the other, his empathy and sympathy for other people is widening and deepening almost every month. It's such a pleasure to watch his moral acuity grow. 

He then told me that he hoped that I could just stay the same, so that we could stay together with the family. But then he paused, and reconsidered. "But I don't want you to hurt too much." I'm not hurting too much, I told him. I also want me to just stay the same if I can't get better. It occurred to me later that I could have said something about the deforolimus -- that I was, in fact, going to try to start taking a drug that was intended to help me "stay the same." But the placebo muddies those waters, and I'm always cautious -- perhaps overcautious -- about offering false hope. 

I approve this message

Got a call for Dr. S last night -- Ariad's doctors agree, my scans are stable enough to enroll in the deforolimus trial. She also mentioned that she had been e-mailing with my NY doctor, and he was also on-board with the decision to take a shot at the trial. So I'm going to go for it sometime next week after I finish a course of antibiotics I'm taking. 

I'll have much, much, much more about the drug and trial in upcoming weeks. Probably not so much the substance of it, but the psychology. In the meantime, here's an abstract (emphasis added) of an encouraging deforolimus sarcoma trial published in January:

Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies.

Mita MM, Mita AC, Chu QS, Rowinsky EK, Fetterly GJ, Goldston M, Patnaik A, Mathews L, Ricart AD, Mays T, Knowles H, Rivera VM, Kreisberg J, Bedrosian CL, Tolcher AW.
Cancer Therapy and Research Center, Institute for Drug Development, The University of Texas Health Science Center, San Antonio, TX, USA.
PURPOSE: This phase I trial was conducted to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of deforolimus (previously known as AP23573; MK-8669), a nonprodrug rapamycin analog, in patients with advanced solid malignancies. 

PATIENTS AND METHODS: Patients were treated using an accelerated titration design with sequential escalating flat doses of deforolimus administered as a 30-minute intravenous infusion once daily for 5 consecutive days every 2 weeks (QDx5) in a 28-day cycle. Safety, pharmacokinetic, pharmacodynamic, and tumor response assessments were performed. 

RESULTS: Thirty-two patients received at least one dose of deforolimus (3 to 28 mg/d). Three dose-limiting toxicity events of grade 3 mouth sores were reported. The maximum-tolerated dose (MTD) was 18.75 mg/d. Common treatment-related adverse events included reversible mouth sores and rash. Whole-blood clearance increased with dose. Pharmacodynamic analyses demonstrated mammalian target of rapamycin inhibition at all dose levels. Four patients (one each with non-small-cell lung cancer, mixed müllerian tumor [carcinosarcoma], renal cell carcinoma, and Ewing sarcoma) experienced confirmed partial responses, and three additional patients had minor tumor regressions. 

CONCLUSION: The MTD of this phase I trial using an accelerated titration design was determined to be 18.75 mg/d. Deforolimus was well tolerated and showed encouraging antitumor activity across a broad range of malignancies when administered intravenously on the QDx5 schedule. On the basis of these overall results, a dose of 12.5 mg/d is being evaluated in phase II trials.

Patient power

I've been thinking a lot about clinical trials lately, as you'd imagine, and one of the things I've been wondering what percentage of drugs at a given stage of trial eventually make it to market. 

I tend to think about it in sports terms -- that for every 20,000 high school basketball players, maybe 10 will play in division 1, and for every 100 D1 players, maybe five or ten make the league. But this is obviously vague, plus it leads to inappropriate analogies: Is this upcoming cancer drug a seven-foot-gazelle, or a 5' 11" point guard who shoots too much? So I was interested to see this passage in a Forbes article about the perils and possibilities of patient-directed medical research:

The patient groups are filling a void in drug research created by the industry's legitimate fear of failure. Biotech executives dread what they call "the valley of death," the period of time between a drug's conception in a lab and its first clinical trial. For every 10,000 would-be medicines chemists create, only one makes it to market. But if a drug has already been through enough tests in cell cultures and lab animals to justify starting clinical trials, the odds of success have risen to one in nine. Put the substance through early clinical trials with a few dozen patients, and the odds jump to one in six. At some point a drug for even the most uncommon disease becomes every bit as appealing to drug companies as an untested potential heart treatment or impotence pill.

I'm not sure I completely believe this -- one in nine drugs in phase-1 trials eventually make it to market? -- but it's encouraging. The rest of the article is interesting as well, and even features a quote from sarcoma celebrity and all-around oncological badass Dr. George Demetri. It's clear that there are highly-motivated and talented individuals (many with business expertise) who can make good things happen faster than they would otherwise, especially for rare conditions that may not have the "market share" to immediately attract pharma dollars. But the emotions involved are intense. Forbes describes prostate-cancer advocates running amok against doctors skeptical about the evidence backing an investigational drug. I get both the advocacy side -- just try to keep me away from something that may work -- and also why some kinds of advocacy absolutely are not helpful to researchers trying to practice good science and good medicine and minimize unintended consequences.

Sarcoma, incidentally, has at least one collaborative group pushing to link researchers at different institutions and secure funding for trials. Though the Sarcoma Alliance for Research through Collaboration was founded by academic researchers, there's at least one seat for a patient-advocacy organization on its board, and they sponsor an array of collaborations, studies and trials.

Banned

The Berkeley Bowl is the greatest supermarket on earth. It's where I learned that cheddar doesn't have to be bright orange and that you could purchase random spiny little chunks of fish to make a delicious broth, steps in a 20-year-plus journey of becoming ever-more engaged by food and cooking. But it's a weird place, as the Los Angeles Times explains:

The produce emporium -- one of the nation's most renowned retailers of exotic fruits and vegetables -- creates its own bad behavior. Kamikaze shoppers crash down crowded aisles without eye contact or apology for fender-benders. So many customers weren't waiting to pay before digging in that management imposed the ultimate deterrent: Those caught sampling without buying will be banned for life -- no reprieves, no excuses. (Not even "I forgot to take my medication.")

Raphael Breines, who was ejected last year for eating on the premises, said he couldn't decide between two types of apricots, so he sampled both. Security stopped him in the parking lot.

"They treated me like a thief," said the 37-year-old park planner, who was photographed and required to sign a no-trespass agreement. "Technically I was stealing, but I wasn't trying to hide anything. I was just deciding which type of apricot to buy."

Breines, a longtime customer, sent an apology letter, asking to be reinstated. His request was denied.

The really great part of this -- and why I go off-topic to link to the piece -- is the fate of John Glionna, the reporter. He has been, you guessed it, banned from the Berkeley Bowl for life.

'Heal me, my darling'

Just because: Ben Harper, covering "Sexual Healing." (Also solo.)

And to make your day: Stevie Wonder doing "Superstition" live on Sesame Street in 1973. (The little kid dancing at the top of the stairs is my hero.)

And hey, to make my day: My little tune-fest this morning (which I've spared you most of), made me think of my rinse-cycled iPod so, with some trepidation, I plugged it in.

It worked!

It will be interesting to see if it holds up -- often, exposure to water leads to corrosion that destroys electronics over time -- but things are looking good for the moment. I didn't do anything much for it except leave alone for a few days and run it briefly through the dryer.

Update: Unsurprisingly but disappointingly, it didn't hold up.

Next time, bring up the weather

Doctors fall short in comforting cancer patients:

Researchers taped 20 exchanges between cancer patients and their oncologists and surgeons at a VA hospital. They found that the docs did provide a bit of empathy, but ignored most instances where patients expressed worry about treatment, sickness and death.

Because, you know, why would a patient want reassurance about treatment, sickness or death?

¡Viva México!

Here's a happy thing from my life: Tuesday was Mexican Independence Day, when our neighbors to the south threw off the shackles of the Latin American rogue state Spain (or so John McCain would call it -- sorry, sorry, couldn't resist). Señor E., L. and myself celebrated with chiles en nogada; poblanos stuffed with picadillo, then topped with a creamy walnut sauce studded with bits of pomegranate. The pepper, sauce and pomegranate deliciously form the red, green and white of the Mexican flag. Although I was feeling quite sick for most that day, I Tylenoled up and felt well enough to gorge myself on the chiles, saffron rice and brownies topped with cajeta, an ultra-rich goat's milk caramel.

Embracing uncertainty

I had a scan yesterday, and the news was good -- mostly. (It would be really nice to have unambiguously positive results from a study, but it's just not in the cards.) My lymph nodes are all the same size, there are no new mets, my disease is technically stable. The pictures and a whole lot of my blood is now being shipped to Ariad, where they will review the information and determine if I am eligible to participate in the deforolimus study. If I get the OK, I'll probably start on the drug or placebo in late September or early October, just after my birthday.

So why don't I feel exultant? Well, I've been wiped out with another mysterious fever for the last couple of days, and in the interlude yesterday between the scan and the doctor's visit, I managed to put my iPod through the wash. (It looks great, but no longer works.) Also, the collapsed lung that had completely healed last month is back in a big way, and it may require intervention at some point. Fortunately, my nightmarish pleurodesis is still somewhat in effect, adhering the lung to the pleura at a couple points, so hopefully the lung won't completely fall down and require immediate action. The scan also revealed several small, hollow cysts on the surface of the lung, which my doctor and the pulmonologist she consulted believe are the source of my collapsed lungs. What's the source of the cysts? We don't know, but some sort of respiratory infection is a possibility. The tiny nodule they found in my last study, incidentally, occupies a piece of real estate that once contained one of these cysts, so they are now more confident that the nodule is not a malignancy. 

As I'm reading this, it's sounding pretty good, so let me try to explain why I'm so anxious. Part of the anxiety is just a learned response; I've gotten a lot of bad news over the last two years. Part of it is the fear of any cancer patient that something is lurking invisibly deep within the body, biding its time, lurking and waiting to rear up and do harm. Part of it is that I know of several epithelioid sarcoma patients who are dealing with pneumothoraces, some with visible lung mets, some without. (Have you had your lungs collapse four or five times in six months? No? Then you can see why I'm not convinced this has nothing to do with the cancer.) 

It comes down to the uncertainty, I guess. One of my mantras throughout this illness has been that we need to learn how to embrace uncertainty, or at least live with it, because the only certainties we're going to get are going to be bad. That's true, but it's a hard way to live. I'm trying, though.

David Foster Wallace

I found out that David Foster Wallace killed himself last night, and the news made me sick. My relatively brief and shallow acquaintance with his writing changed permanently how I see John McCain, right-wing talk radio, the nervous system of a lobster, professional tennis, television commercials, cruise ships, irony, grammar and literary fads. (I wonder what the hell might happen if I ever read his fiction seriously.) Years ago, driving the car, I chanced upon an interview that Wallace did with Michael Silverblatt, and I had to pull over. His erudition, passion and richly timbered voice captivated me. Here's a little bit of Wallace from another interview:

I had a teacher I liked who used to say good fiction’s job was to comfort the disturbed and disturb the comfortable. I guess a big part of serious fiction’s purpose is to give the reader, who like all of us is sort of marooned in her own skull, to give her imaginative access to other selves. Since an ineluctable part of being a human self is suffering, part of what we humans come to art for is an experience of suffering, necessarily a vicarious experience, more like a sort of “generalization” of suffering. Does this make sense? We all suffer alone in the real world; true empathy’s impossible. But if a piece of fiction can allow us imaginatively to identify with a character’s pain, we might then also more easily conceive of others identifying with our own. This is nourishing, redemptive; we become less alone inside. It might just be that simple.

I was also moved by his commencement address at Kenyon College (I'm a fan of the genre), some of which I'll quote below:

And I submit that this is what the real, no bullshit value of your liberal arts education is supposed to be about: how to keep from going through your comfortable, prosperous, respectable adult life dead, unconscious, a slave to your head and to your natural default setting of being uniquely, completely, imperially alone day in and day out. ...

If I weren't so tired and depressed by the whole thing, I'd go on and on. Maybe I will later. In the meantime, you can find links to some of Wallace's journalism here. 

'Survivors' by Errol Morris

Worth watching:

Donne and death

A nurse unexpectedly loses a patient:

What can one do? Go home, love your children, try not to bicker, eat well, walk in the rain, feel the sun on your face and laugh loud and often, as much as possible, and especially at yourself. Because the only antidote to death is not poetry, or drama, or miracle drugs, or a roomful of technical expertise and good intentions. The antidote to death is life.

Shaggy dog story

The dog cancer took from me is shaggy, lovable and weighs 130 pounds. L. will kill me for saying it, but she was a lousy dog by any conventional definition -- but lousy in grand and amusing ways, the kind of bad dog that someone might write a best-selling memoir about.

Her behavior was bad, but her heart was good. She would follow us around the house, lying down with a sigh and a thud when we settled. Her head was heavy and noble, and she would lay it on my feet when I sat on the couch. When she desired petting, she would sidle up in front of someone and present her mighty expanse for a rub, leaning into her human by ever greater degrees, until they staggered back or braced themselves against something solid enough to take the weight, something like an anvil. She was a fierce, if overzealous, protector of her home and family; woe to the UPS man approaching the door or the house cantering down the road. Abby was always ready defend our home against shipments of Amazon books or potentially rabid equines.

Her appetite was ravenous, even if dog food was often too pedestrian for her tastes. Her great size and athletic ability meant that nothing on the counters was safe from her predation; she mastered the trick of setting her feet, rising slowly and silently like some great crane or drawbridge, and snatching a peanut butter jar, baguette or small child from the countertop. With her prize tucked within her capacious jaws, she would drop to the floor with a snap, then stealthily but quickly run to her dog bed, or “office” as I called it, which would at times be littered with plastic wrap, ceramic bowls, even the occasional pilfered chef’s knife. To this day, almost two years since she’s been gone, I still find myself setting my cooking mise en place on top of the refrigerator -- but not on the edge, because Abby could occasionally manage to snare things from the fridgetop. This was a big dog.

It was the refrigerator, ultimately, that proved her undoing in our home. Before I was diagnosed with epithelioid sarcoma, I spent about seven months undergoing a succession of exploratory surgeries and the like while my tumors grew ever-more symptomatic. By the time I was diagnosed with the cancer and began chemotherapy, I had already been staggered by the illness for some time. With my health troubles, and with two kids four and under in the house, Abby wasn’t getting walked and her behavior began to decline precipitously. She finally learned how to open the refrigerator -- a jab of her long nose into the seals. We made a few feeble attempts to stack furniture in front of the door (she moved it out of the way easily), but it was clear that we needed to focus on our kids and my treatment, not on cleaning up the carnage that results when a dog learns to open the door to culinary paradise at will. In one of the most loving things anyone has done for us, a friend drove her nearly 300 miles to a Newfoundland rescue group, which exercised and rehabilitated her and found her a great adoptive home.

Now I find myself increasingly longing for another dog, and resenting the uncertainty that shrouds my present and future. I could walk and groom a dog now -- but what about six months from now? (Hell, two months from now?) What if I get sicker? I can’t summon any logic to support the proposition that getting a dog now makes sense. But I want one anyway.

Cocktail hour

Greg's comment below reminded me of this Wall Street Journal article from last year. It emphasizes childhood tumors, but also features some adult cancer patients who are pursuing a "cocktail" approach to chemotherapy.

Neil Hutchison, 45, isn't a doctor. A defense-contractor recruiter, he's part of a growing underground pushing the edge of medicine to find combinations of anticancer agents to save themselves or loved ones. Many of the medicines Sam takes haven't been tested in clinical trials for his disease. Some are meant for other illnesses; others are still in animal testing for safety and efficacy. But the fact is that Sam, who suffers a rare and often-deadly cancer of the nerves, is otherwise almost certain to die. Hence Mr. Hutchinson's decision, as he puts it, to play "lab rat" with his son.

...

But Mr. Hutchison is pursuing what many researchers believe is the most promising approach for curing or curbing cancer, which killed about 565,000 people in the U.S. last year. Because cancer seems to eventually overcome most individual therapies, researchers for a decade have advocated using combinations of new, targeted therapies on the theory that the best hope lies in cutting off all known avenues for the cancer to grow.

Trials of such methods have been slow to gain traction. "Everyone knows the future of cancer treatment lies in cancer cocktails," says David Kessler, dean of the school of medicine at the University of California, San Francisco. Dr. Kessler says the Food and Drug Administration needs to undertake an effort similar to one it did when he was commissioner in the 1990s, when it amended the drug-approval process to speed approval of AIDS-drug combinations. "What's missing today is leadership."

You gotta fight

Sick Guy, Sr. passed on this Steve Lopez column about the importance of second opinions. 

Lopez's sister's oncologist recommended whole-brain radiation after ovarian cancer metastasized, a treatment that has immediate and often severe side-effects. But after the writer described the case to first one, then several, experts no one thought whole-brain radiation was indicated. Lopez's sister got a workup and formal second opinion at a top facility, which recommended more targeted "gamma knife" radiation. Whole-brain radiation was barely considered. Whether out of misplaced personal pride, the limitations of your health plan, or the limitations of in-network facilities (which in this case did not include a gamma knife facility), docs don't always make the right call.

Of course, this story suffers from the Teddy Kennedy problem -- how am I going to get several experts on the phone if I'm not a senator or Pulitzer Prize-winner? You probably aren't. But supportive communities like the Sarcoma Alliance bulletin board offer access to quite a bit of knowledge, and most insurance companies and doctors will support at least one formal second opinion.

Rethinking the war on cancer

One of the many disconcerting things about getting cancer -- or having a friend or loved one get it -- is the sudden undermining of your sense of progress. (Literally: I tend to think of "progress" as a good thing, and during one of my early doctor's visit I was pleased when the fellow said something about progress after a CT scan. She meant, of course, that my disease was advancing.) For all the new understanding of the genome, the new smart drugs, the new collaborative research centers and the advances in basic biology made every day, the outlook for many people with metastatic cancer isn't appreciably better than it was 30 years ago. 

In an excellent, if depressing article, Newsweek tries to offer a bracing corrective to the usual puff coverage of new advances, drugs and, er, progress. The idea isn't so much to knock down hope as it it is to suggest that we need a change in how cancer research is approached and funded. The article is here.

A corrective:

She has seen real progress in her 19 years in practice, but the upbeat focus on cancer survivors, cancer breakthroughs and miracle drugs bothers her. "The metaphor of fighting cancer implies the possibility of winning," she said after seeing the last of that day's patients one afternoon. "But some people are just not going to be cured. We've made tremendous strides against some cancers, but on others we're stuck, and even our successes buy some people only a little more time before they die of cancer anyway." She pauses, musing on how the uplifting stories and statistics—death rates from female breast cancer have fallen steadily since 1990; fecal occult blood testing and colonoscopy have helped avert some 80,000 deaths from colorectal cancer since 1990—can send the wrong message.

And some precedent for possible new approaches...

At the same time that molecular biologists were taking the glamorous, "look for the cool molecular pathway," cojones-fueled approach to seeking a cure, pediatric oncologists took a different path. Pediatric cancer had long been a death sentence: in Farber's day, children with leukemia rarely survived more than three months. (President Bush's sister Robin died of the disease in 1953; she was 3.) Fast-forward to 2008: 80 percent of children with cancer survive well into adulthood.

To achieve that success, pediatric oncologists collaborated to such a degree that at times 80 percent of the children with a particular cancer were enrolled in a clinical trial testing a new therapy. In adults, it has long been less than 1 percent. The researchers focused hardly at all on discovering new molecular pathways and new drugs. Instead, they threw everything into the existing medicine chest at the problem, tinkering with drug doses and combinations and sequencing and timing. "We were learning how to better use the drugs we had," says pediatric oncologist Lisa Diller of Dana-Farber Cancer Institute and Children's Hospital Boston. By 1994, combinations of four drugs kept 75 percent of childhood leukemia patients—and 95 percent of those enrolled in a study—cancer-free. Childhood brain cancer has been harder to tame, but while 10 percent of kids survived it in the 1970s, today 45 percent do—a greater improvement than in most adult cancers. (To be sure, some scientists who work on adult cancers are sick of hearing about the noble cooperation of their pediatric colleagues. Childhood cancers, especially leukemias, are simpler cancers, they say, often characterized by a single mutation, and that's why the cure rate has soared. Neutral observers say it's a little of both: pediatric-cancer scientists really did approach the problem in a novel, practical way, but their enemy is less wily than most adult cancers.)

ES Facebook group launched

I mention this mainly for completeness, since I'm not myself a Facebook member, but someone has launched a "causes" page for epitheloid sarcoma on the social-networking site. The gateway is here. It seems like a worthy venture, but one line from the page gave me pause. Caroline, the page owner, writes, "It is proven that it does not respond to chemotherapy." 

This is verifiably false; this paper doesn't quite get to core of the issue, since it's in vitro, but it shows that ES cells are killed by paclitaxel, aka Taxol (the standard second-line treatment for ES, and many other sarcomas, is now a combination of gemcitabine and docetaxel, another taxane). It is true that ES is highly chemo resistant, and it may be true that chemotherapy does not have a proven overall survival benefit for ES. The jury is still out, unfortunately. But based on my response to chemo and the anecdotal accounts of others, I'm convinced that at the very least chemo can increase progression free survival. I'm puzzled as to why more than a few people dealing with ES want to say that chemo is useless. The situation is bad enough -- let's not make it any worse with overly sweeping statements about the disease's drug resistance.

Studying loss

An arresting (but difficult to read) article from the Los Angeles Times about a college course in which students visit autopsy rooms, hospices and convicted murders to learn about death and loss. College students study death to learn the meaning of life:

For the last decade, Bowe has led her classes of 30 students into the refrigerated tombs of bodies stacked bunk-bed-style in the morgue and into hospice bedrooms, glowing from television screens, occupied by the sickly and soon-to-die. She guides them through the barbed-wire fences of Northern New Jersey State Penitentiary, past the outdoor recreation kennels where gang members sweat and swear, to a law library where they sit down with murderers.

Her students are from suburban small towns and inner cities. They enroll in Bowe's class because they are curious about her unusual field trips. But something more powerful also draws them here: a need to know how we die, and why. What happens to our bodies, and is there such a thing as the soul?

Scaring the kids (or, still more matters culinary)

Another thing that a doctor said to me just after I got cancer that seemed a little obvious at the time, but took on more meaning later was: "You know, you didn't do anything to get this." 

I thought of that yesterday when I heard about a new TV commercial from Physicians Committee for Responsible Medicine attacking hot dogs. The lede of the AP story explains: 

A new TV commercial shows kids eating hot dogs in a school cafeteria and one little boy’s haunting lament: “I was dumbfounded when the doctor told me I have late-stage colon cancer.”

Nice! 

The little boy, as well as two others making testimonials in the ad, do not have cancer. (The use of "dumbfounded" by a child was a clue as to the scripted nature of the thing.) I had initially thought the ad was from some kind of vegan group -- the PETA milk-causes-acne crowd -- but I guess that isn't the case. Still, I'm haunted by the thought: What if the vegans are right, and the rest of us will fade away, leaving the world to slender, tight-lipped folks publishing abrasive web sites and walking around in soy shoes... 

Weird

I'm writing this with my ear half-cocked for the school bus. B. is riding home on the bus for only the second time ever, and I am sitting here waiting to usher him inside after the first day of second grade. I am armed with cookies and cold milk. It's a little surreal, but very sweet. At least I'm getting something out of sarcoma...

Teddy

When I became depressed last summer after finishing my initial blitzkrieg of chemotherapy and radiation, I went to see a psychiatrist who spends a lot of time working with cancer patients. 

He said something to me that seemed obvious then, but has grown more meaningful with time. I can't do it justice, but the pep talk went something like this: "Cancer isn't all you're about. It needs to be attended to, but it can't become everything you are. You are still the person you were before you got sick, and you need to honor that person by making room for your old passions and pleasures -- and finding new ones."

(Obviously, I've been crackerjack on that advice -- writing a cancer blog under the pseudonym Sick Guy. But no, no -- I am honoring who I was, who I am. I've always had a dark sense of humor.)

I was reminded of the doctor's words when I saw Teddy Kennedy speak at the Democratic convention. I was moved more by his presence than what he said. The contingency of it -- no announcement beforehand lest something go wrong and lead to a cancellation -- echoed the uncertainty of my own cancer experience. More echoes: That hair, thinned but still unmistakable, the stool behind the podium, the physical support of his wife, his energetic defiance. 

Kennedy didn't go to the convention because he wanted to hear a house go wild one last time, though I'm sure that was nice. He went because he is passionate about his party's candidate, and because he wants to do one more big thing before he dies. He's doing what all of us dealing with this illness are trying to do, put one foot in front of the other, however laboriously, for the people and causes we love. Even if, especially if, it costs us. My great work is with my family. His is... broader. 

The political blogger Ezra Klein elaborates:

In the last few weeks, I've spoken to a couple Kennedy aides who all told me the same thing: Health care. Kennedy has told them that this is his final crusade. Aides who work in other legislative areas have been told that their issue areas are going to almost dissolve, and they'll become something like support staff for the health team. Kennedy means to pass a bill. He means to muster the full force of his legislative talents, his sprawling staff, his longstanding relationships, and even the poignancy of his condition. It will be his legacy. It is his dream.

Times to me: 'Get off the couch!'

I wasn't going to comment on the New York Times cancer and exercise story (I don't want to be a NYT clipping service), but I kept thinking about the article hours after reading it, specifically this part:

Other studies indicate that moderate exercise has additional benefits like strengthened immune function and lower rates of recurrence. Studies at Dana-Farber found that nonmetastatic colon cancer patients who routinely exercised had a 50 percent lower mortality rate during the study period than their inactive peers, regardless of how active they were before the diagnoses.

I wondered how they figured that out, so I read a little more about the 2006 study. It made sense to me that having a more serious presentation of colon cancer would make you more likely to be sedentary after treatment and also more likely to die from a recurrence or other cause. I wanted to see how they adjusted for that. The study's authors say they can't completely eliminate that possibility, but they picked patients at the same stage of the disease who had similar surgery and chemotherapy, adjusted the data for other risk factors of death, and eliminated from the study population people who died within six months of having their physical activity assessed. That said, the study doesn't have much to say about causation or the mechanism by which exercise might lower recurrence risk. 

Nonetheless, an editorial published along with the study used these results and others relating to breast cancer to tell patients that it's "time to get moving." If you're tempted, exercise seems to provide measurable benefits at about 9 MET hours  a week (don't ask; it's the equivalent of four or five 30-minute brisk walks) after breast cancer and 18 weekly MET hours (four or five 30-minute jogs) after colon cancer. Shockingly, there's no epithelioid sarcoma data. I don't know if working out that much is possible for me, but I'm at least going to take a walk this afternoon...