Saturday, August 30, 2014

Curcumin and Cancer

Interesting article on Curcumin and cancer fro MedicalXpress. It's not about lymphoma, but it got me thinking.

The article is called "Curcumin Blocks the Metastasis of Colon Cancer by a Novel Mechanism." Curcumin is an ingredient in the spice Turmeric, which is often used in Indian cuisine because of its flavor and bright yellow color. (And it makes an acceptable substitute for saffron in Risotto Milanese, but don't tell anyone in my family I said that.) It has long been thought that Curcumin has an effect on cancer, perhaps in blocking metastasis and spreading of colon cancer. (I say "thought to" and "possibly" because I can't find anything that doesn't use that kind of fuzzy language.) No one is rejecting the idea that Curcumin might be helpful, but it isn't being used as a common treatment for cancer, either. It isn't absorbed easily by the body, and that's one of the problems.

The study described in this article might move us away from the fuzzy language. Some researchers have found the mechanism that makes Curcumin block metastasis. It activates an enzyme that blocks a protein called cortactin in colon cancer. Cortactin is necessary for cells to move. Therefore, blocking it will keep cells (including cancer cells) from moving from one part of the body to another. It won't necessarily kill the cancer cells, but it will keep them in one place. That's a big issue for certain cancers.

Reading this reminded me of a lot the advice I got when I was first diagnosed. Someone did recommend I eat a lot of turmeric. Someone else suggested I buy some kind of juice that would cost about $15 a day. Someone else sent me a link to a special trampoline that would keep my lymphatic fluid moving and not turn to sludge (which was, they said, probably what caused my lymphoma). Someone else said I should cut out sugar.

They were all well-meaning, and I never got mad at anyone for offering me advice. They were all very sincere -- every one of them had "read it somewhere."

But, despite seeing something online or in print, none of it was ever subjected to any kind of rigorous study to see if it actually worked. Some of them might have been studied "in vitro," in a laboratory, but not "in vivo," in an actual patient. That matters. As we see more and more, it's not just the cancer cells that matter, but all of the stuff happening around the cells, all of the processes that occur to keep a cancer alive, that matter. So dropping some South American juice on a cancer cell in a petri dish and watching it die really doesn't tell you much about how that juice -- after it has been consumed and processed by the body and then sent to the cell -- will behave.

So even though that Curcumin study is important for colon cancer patients, I think it's important for us Follicular Lymphoma patients, too, but for a different reason. We all want quick fixes -- we all want a juice to drink or a food to avoid to help us. But cancer isn't that easy to deal with, as much as we'd like there to be. And Follicular Lymphoma is even harder than other cancers, given its nature. We might decide that eating Massaman Curry every day for lunch is what has made our lymph nodes shrink, when really, it has been the waxing-and-waning that sometimes occurs no matter what we do. There's no real way to tell, without the kind of rigorous study that comes from a formal clinical trial.

(And I would absolutely volunteer for a clinical trial that involved eating Massaman Curry every day, especially if it was also testing whether Pad Thai helped with Curcumin absorption.)

I'm all for doing things that help us feel good, whether it's eating curry or jumping on a trampoline. But when it comes to really attacking our lymphoma, I think science has to win out.

And if there's one important thing that I got from this article, it is this:

When my wife and I go out for our weekly lunch together, it's going to be at our favorite Indian restaurant. Because now I am have a really bad craving for some curry.

Thursday, August 28, 2014

Rituxan Maintenance for Follicular Lymphoma

The newest issue of the Journal of Clinical Oncology has a report from the RESORT trial (the name stands for Rituximab Extended Schedule or Re-Treatment. Basically, the trial wanted to see which was more effective: Rituxan Maintenance (their "Extended Schedule") or just waiting until treatment is needed again, and then giving more Rituxan ("Re-Treatment").

In a nutshell, they believe that Re-Treatment when needed is the choice over Rituxan Maintenance for Follicular Lymphoma patients with low tumor burden.

Let me repeat the important part of that: with low tumor burden. The trial focused on patients with this characteristic, and the article is clear about what this means. Basically, low tumor burden has to do with size (less than 7 cm), location (not pressing on any organs), and grade (no B symptoms). What they say about Rituxan Maintenance doesn't apply to patients with more aggressive forms of Follicular Lymphoma. That's important to remember.

It's also important to remember that the RESORT trial is focused on patients whose initial treatment was straight Rituxan. It doesn't necessarily tell us anything about patients who had Rituxan Maintenance after chemo.

So this is fairly limited bunch of folks we're dealing with here.

As for the specifics of the trial: 289 FL patients were given four doses of Rituxan as a first treatment. They were then split randomly into two groups. The first group received Rituxan Maintenance -- one dose every three months. The other group was only given Rituxan when it was necessary, that is, when their lymphoma progressed enough to need it. For both groups, this went on until the Rituxan stopped working ("treatment failure").

For the patients receiving Maintenance, the median time to treatment failure was 4.3 years. For those in the Re-Treatment group, it was 3.9 years. Statistically, there really isn't any difference between them. But over that time, the Maintenance group received a median of 18 doses of Rituxan, while the Re-Treatment group received just 4.

That seems to be the kicker for the researchers -- a few extra months before treatment failure requires an additional 14 doses of Rituxan. And with those doses comes the costs in time and money and whatever emotional costs come with going for treatment. So their conclusion is: for Follicular Lymphoma patients with low tumor burden who received Rituxan as an initial treatment, Rituxan Maintenance really isn't worth it.

Interestingly, the researchers point out that they would love to see a similar trial involving patients whose initial treatment was chemo + Rituxan, comparing those who get Maintenance with those who are Re-Treated with Rituxan as needed. Maintenance is a common practice, but maybe there's reason to ask whether or not there's a better way?

The JCO article was accompanied by an editorial called "End of Rituxan Maintenance for Low Tumor Burden Follicular Lymphoma." It's a title that pretty much sums up the author's position -- he thinks the RESORT trial results tell us everything we need to know. The author doesn't only refer to the RESORT article, but also to an article from March in The Lancet that showed that Rituxan Maintenance in a similar group of patients (low tumor burden Follicular Lymphoma) resulted in a better chance of holding off the lymphoma from returning, compared to those who watched and waited. HOWEVER, the Overall Survival of the two groups was virtually the same, and there was no difference between the two groups in terms of transformation. So while the article from The Lancet might seem like a win for Rituxan Maintenance (and that's certainly the way I wrote about it, as you can see from the link), looking at different outcomes might paint a different picture of that data.

(And, to be fair, The Lancet article and the RESORT article compared two different groups. One said Maintenance was better than watching and waiting, while the other said it was not as good as treating as needed.)

My conclusion?

As with many things related to Follicular Lymphoma, we still have no real, solid evidence that one strategy is definitely better than another. Despite the confidence of that title, I don't think we've seen the "End of Rituxan Maintenance" for FL patients with low tumor burden. It might provide a push for a patient or oncologist who is sitting on the fence, but I'm sure there are plenty of folks who will continue the practice. The RESORT results didn't say Maintenance was bad or harmful, only that there might be a better way.

I can remember talking to Dr. R about Maintenance after my six rounds of Rituxan. He talked me out of it, saying there was better evidence that Maintenance worked after chemo than after straight Rituxan, and that his philosophy was to treat when necessary (very much in line with the Re-Treatment approach from RESORT). Dr. R certainly seems wise, four and a half years later, when I still haven't needed Re-Treatment of any kind.

Of course, one patient does not make a trial, so my isolated experience doesn't mean much. The lesson, instead, from my experience is that an open, two-way conversation with your oncologust is necessary when it comes time for treatment.

Tuesday, August 26, 2014

Visit to the Oncologist

I had an oncologist appointment this morning. Everything looks fine.

To be honest, this appointment snuck up on me -- I forgot to put it on the calendar, and I only remembered because it they gave me a reminder call yesterday. This was about 3 months since my last visit; I think I made it a month shorter than usual because I knew once school started up for everybody that things would get their usual crazy, so I'd do it before then.

I think that's a good thing that I had forgotten about it. Forgetting = not worrying = not having any problems to worry about. It was kind of the theme for this visit.

For whatever reason, Dr. R didn't have me do blood work first, like he usually does. Maybe I came in late? I still get confused about my appointment time. Because the practice is now officially a branch of the cancer hospital, I have two separate appointments -- one for a blood draw and one for the onc visit. So when they say the appointment is at 11:15, I don't know if that's for the onc or the blood. So maybe I was supposed to be there for blood work at 11:00, so he took me in at 11:15 so I would stay on schedule for him? I don't know. Still not crazy about this new set up.

Anyway, the physical exam was fine. He didn't find anything popping up that shouldn't be popping up anywhere. And then he gave me his serious face and said, "I know we've been kind of going back and forth about this, but we should probably think about a scan soon...."

"Wait," I interrupted. "I had a scan in June."


My wife backed me up on this.

He looked at my online records and saw that I had indeed gotten a scan in June. We talked about the results, even though we had talked about them back then. He was pleased with the results, as he should have been. And then I gave him crap for the rest of the visit.

"Jeez, doctor. I've been coming here for six and half years. I thought I was more memorable than that."

He smiled. "I think it's better for you to not be memorable."

And he's right. If I was a patient who was in the middle of treatment, or if I was a particularly tough Follicular Lymphoma case that kept recurring, or if the scan was really troubling, then maybe I would have been on his mind. But I'm just a slow-growing, waxing-and-waning, see-you-every-four-months-for-a-few-minutes kind of patient. And I can't complain about that. I'll take forgettable if those are my choices.

Plus, it's just so much fun to give him a hard time about something.

It turned out that, because I went to a new place for the scan, he was looking in the wrong place in my file for the information. An honest enough mistake, I guess.

He ordered blood work after that, and gave me a thumbs-up 5 minutes later when everything there appeared normal.

So overall, it was a good visit. An unexpected one, but a good one. I go back in late December -- I hope to have no health news for you until then.

Saturday, August 23, 2014

How Stem Cell Transplants Work

I haven't listened to Yale Cancer Center Answers recently, so when I visited their web page this week, I saw that one of their shows in June was on Stem Cell Transplants. It's a pretty good introduction to the topic.

(The link above will take you to a pdf of the show's transcript. If you'd like to listen to the show, click here and scroll down to the June 15, 2014 link.)

Yale Cancer Center Answers is a weekly radio show put together by the Smilow Cancer Center at Yale, focusing each week on a different cancer-related topic. There are three hosts, and they interview a cancer specialist from Smilow each week -- usually a researcher, though sometimes a nurse or social worker if the topic calls for it.

For the Stem Cell show, the guest was Dr. Stuart Seropian, a blood cancer specialist; he is interviewed by Dr. Steven Gore, who is Director of Hematological Malignancies at Yale.

As I said, I think the interview does a nice job of laying out the basics of how a Stem Cell Transplant works, the difference between Auto and Allo transplants, as well as some of the issues related to transplants, like Host vs. Graft Disease, and how to become a donor.

While the interview does a great job of laying out the basics of a Stem Cell Transplant, it doesn't get too deep into things like more recent research, I recommend a trip to's STC page. Great information, easy to find.

It's interesting to think about the role an STC might play for some of us in the future. It will probably be an option for us for a very long time, though given that it is essentially a chemotherapy procedure, I don't know if some of the procedures being developed -- targeted inhibitors, for example -- will ultimately replace chemotherapy. That will mean a big debate about the goal of Follicular Lymphoam treatment -- to cure? or to control?

Of course, that debate is already happening.

In the meantime, it's good to know all we can about the options available to us.

Wednesday, August 20, 2014

Men, Women, and Cancer

U.S. News and World Report has an interesting article online called "Cancer: Men Are From Mars, Women Are From Venus." It gets into the differences between men and women when it comes to cancer  -- not so much the physical differences, but the emotional and mental ones that come from a cancer diagnosis and everything that follows.

Women tend to be better communicators when they are faced with a diagnosis. Men tend to retreat to their cave.

Women tend to see things as a process, and look at the big picture. Men just want to get back to their old normal activities.

Women look online for support. Men just want to fix things.

The article struck me because I saw some of myself in it. As I've said here before, after the initial shock of my diagnosis wore off, I went into a pretty heavy depression, thinking about  my family, especially how they would be provided for. (I remember being thrilled when I realized my kids could collect social security until they were 18.) I came out of it because my wife pulled me out of it. I went into the cave; she made me come out and talk. We were kind of a textbook case.

Of course, the article also points out that these trends are sometimes stereotypes, too -- we don't automatically behave certain ways just because we are men or women. Apparently, in a surprise finding to a study, women spend more time online researching their own or a loved one's cancer. Goodness knows I've spent a little time online....

I think it's good to read about things like this, because maybe they give us a chance to stop and think about ourselves. Sometimes we get so caught up in thinking about our cancer that we don't think about ourselves, if that makes sense. We don't think about how we're handling it, if what we are doing is the best thing to be doing, if circumstances have changed -- if our loved ones are handling things OK.

So I like articles like this, that get me to think about myself. Might even end up starting a little discussion.

Even though I'm a guy, I think that might be a good thing.

Saturday, August 16, 2014

EZH2 Inhibitor for Follicular Lymphoma?

ASH, the American Society for Hematology, has a summer conference on Lymphoma Biology. It ended a couple of days ago. It's much smaller and more focused than the main ASH conference. They also don't make the abstracts and materials public like they do for the main conference. And it doesn't look like there was much about Follicular Lymphoma discussed there.

But I did find this -- a press release from Epizyme, the company that is partnering in creating and testing EPZ-6438, an EZH2 Inhibitor. The presentation focuses on pre-trial and phase 1 trial results. In other words, it's all very early, and very limited -- they only discuss one Follicular Lymphoma patient -- but I think it's worth looking at, since this class of inhibitors seems like it will be a big part of our futures as Follicular Lymphoma patients.

First off, the whole EZH2 Inhibitor thing. EZH2 is the name of a gene that encodes an enzyme, also called EZH2. When there is too much EZH2, a chain reaction is set off. Too much EZH2 enyzme results in the creation of too much histone methylation, a process that leads to bad things happening to some other genes that suppress tumors. [I just erased a paragraph of science-y stuff that I was having trouble following myself. Let's just say this: EZH2 needs to be controlled, because if it isn't, it will allow cells to live for as long as they want to. Next step = cancer.]

EZH2 seems to play a role in a bunch of cancers, both solid and liquid, including some types of Follicular Lymphoma. (Remember -- there isn't just one type of FL. About 22% of Follicular Lymphoma patients have the mutation that is related to EZH2.)

So the EPZ-6438 that is being developed and tested is an EZH2 inhibitor -- it's job is to stop EZH2 from allowing cancer cells to grow willy-nilly.

The presentation at ASH focused on pre-clinical results (stuff they found out in the laboratory) and some phase 1 trial results. As I said, the information about Follicular Lymphoma is pretty limited -- they only report results for one patient, who had stable disease as a result of the treatment. Not an overwhelming endorsement, but enough to move forward.

The pre-clinical results were kind of interesting, too. They combined cells with the inhibitor and CHOP, with good results. Then they tried the individual components of CHOP, and found that just Prednisone helped even more, as did Dexamethasone, another steroid. They also found some activity with BCL2 inhibitors.

It's important to remember that the pre-clinical stuff doesn't involve actual patients; it's just an attempt to narrow down possible options for combinations in later trials.

So what do we have here? A whole bunch of possibilities, and not much else.

Which isn't to say possibilities are bad. It's just really early in the process for this particular treatment.

I'm confident, though, that we'll find something, at some point, that works on EZH2. This particular inhibitor isn't the only one being developed that targets EZH2; the results of research on another possibility were discussed about a year and a half ago in the journal Nature.

I'm also confident that all of this research adds to a bigger picture. Even though EZH2 only effects 22% of us FL patients, our broader understanding of the pathways that lead to cancer can only help researchers as they figure out ways to attack other pathways, as they become known.

So for this research -- right now? Meh. In the future? Lots to hopeful about.

Tuesday, August 12, 2014

Advice for Living with Cancer

I saw an article last week called "Got Cancer? Now What?" written by Lisa Marie Wilson, a cancer survivor, who was also a caretaker for a mother and grandmother who had cancer. It's pretty good advice, especially for someone newly diagnosed.

It's been six and a half years as a cancer patient for me, and reading this brought back some memories.

I like Wilson's advice to be organized early on -- get and save copies of paperwork from each doctor, understand what you'll need to bring to appointments, and make friends with someone from the insurance company. It's been a long time since those hazy first days of diagnosis for me, but I'd also add, bring a friend along who can assist you with all of those things. Another pair of eyes and ears is a big help when your own head is filled with visions of dancing cancer cells. Clarity comes later, when the fog lifts.

She also has some good advice on attitude -- "take the diagnosis as a warning, not a fact." I like the way she put this. Obviously, you need to be realistic, and accept that you have cancer, but you don't need to believe the statistics you read online and take those as a reflection of what your own cancer journey will be. In fact, I'd add something to this list about staying offline for a while, or maybe having that clear-eyed friend read along with you when you go online to make sure you aren't reading the worst.

A couple of other bits of advice on staying positive are helpful, but with some cautions. I absolutely believe in the power of humor, and if you've read some of the very early stuff on this blog from my first year, you know that I'm a great collector of cancer humor. [Which reminds me -- I may need to write a cancer humor post sometime soon. It's been, literally, years since I've done one....] For me, laughing at cancer was a way of facing cancer head-on. And I think it's great advice for people who are equipped for it. For me, I've always been an easy laugh, especially at my own jokes. My wife says I'll always have an audience because I think of myself as so darn funny. But for some people, who may be a little more serious, laughter is going to be forced. And that might just take more energy than you have to spare.

I'm also wary of the "stay positive" advice. Again, I'm a fairly positive person. And I tell my kids, when things are going bad, that the only problem that gets solved by staying in bed is a lack of sleep. Facing the day is the best way to solve a problem. But being positive all the time can be exhausting. There are a few versions out there of responses to the "tyranny of the positive attitude" (I like this one -- less academic). Basically, we're always told that we have to stay positive in the face of something like cancer. And we probably should -- most of the time. But dang it, sometimes we need to just have a crappy day. A day of staying in bed and eating ice cream for lunch and watching Dirty Dancing. And promising ourselves that we'll try to be more positive tomorrow. I think that's a healthy thing to do. We're cancer patients, for crying out loud. We're entitled to a day of cookie dough and Patrick Swayze.

So, overall, I think the article has some very good advice. But, like all advice, I think we need to adapt it in ways that make sense to us. We all deal with cancer differently -- those of us who have it, those of us who care for those who have it, and those of us who aren't sure what to do for someone who has it. The most important things, in my experience, are to communicate with people who can help you, whether they are doctors or caregivers, and to learn as much as you can about your disease, but not so much that you drive yourself crazy.