August 27, 2010: Cancer-Fighting's New Cocktail Party

An article in Business Week, "Cocktails Are Next For Cancer-Drug Makers," highlights what its author calls a new development in cancer treatment. Comparing newly-developed cancer drug combinations to the drug cocktails that have been successful in treating HIV/AIDS, the author says:

"For more than a decade, cancer researchers have been crafting drugs to disrupt the precise cellular processes that fuel cancer, creating a $51 billion market in 2009. So far, the survival benefits have been measured in months, not years. That's because cancer, like the virus that causes AIDS, evolves rapidly to evade a single treatment. Rather than mixing and matching approved drugs, researchers are developing new, targeted combinations that work in tandem to block cancer.

'We're looking to see a radical change in terms of stopping the disease in its tracks,' says Tal Zaks, head of global oncology drug development at Sanofi in Paris. 'The return on investment here is not going to be just evolutionary; it has the potential to be revolutionary.'"

I don't get it. What's so new about chemo cocktails? I got R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) five years ago. Isn't that a targeted drug cocktail?

R-CHOP is concocted of three chemo agents and a steroid, linked up with Rituximab, a monoclonal antibody that does the targeting.

How is this different from what the Business Week article is talking about? Can anyone enlighten me?

July 13, 2010 – Bendamustine Rising

Thanks to Betsy DeParry of the Patients- Against-Lymphoma group on Facebook, for posting excerpts from an article about Bendamustine in the treatment of indolent NHL.

Bendamustine (trade names Treanda, Ribomustin) is a chemotherapy agent that’s been around for decades. It was developed in East Germany during the Cold War, which is perhaps why it was slow to catch on in the U.S. and Western Europe. It’s receiving a lot of attention these days as a treatment option for NHL, either in conjunction with Rituxan or on its own.

The full article is found in the issue of the American Journal of Health-System Pharmacy (2010; 67: 713-723). Authors are Anjana Elefante, Pharm.D., B.Sc.Phm., Clinical Pharmacist, Department of Pharmacy; and Myron S. Czuczman, M.D., Chief, Lymphoma/Myeloma Service, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.

Here are some excerpts from Betsy’s excerpts:

“Bendamustine is an alkylating agent that has a unique, multifaceted mechanism of action. Compared with other alkylators, bendamustine produces more-extensive and long-lasting DNA damage. Bendamustine also inhibits cell-cycle checkpoints, leading to mitotic catastrophe and apoptosis.”

Sounds pretty dire, eh? Well, the “DNA damage... mitotic catastrophe and apoptosis” is actually referring to cancer cells, so that’s not such a bad thing.

“Bendamustine is approved for the treatment of CLL and for indolent B-cell NHL that has progressed during or within 6 months of treatment with rituximab or a rituximab-based regimen. In Phase II and III trials in patients with indolent NHL and CLL, bendamustine has demonstrated response rates of 67–84% as a single agent and median durations of response of 7–21 months. Additional clinical trials are examining bendamustine as a single agent and in combination therapy for the treatment of hematologic malignancies and solid tumors. Adverse events associated with bendamustine are typically mild to moderate and can usually be managed with supportive care.”

Sounds pretty encouraging.

“NHL is the most common hematologic cancer and the sixth most common cancer in the United States, with an estimated 65,980 new cases and 19,500 deaths occurring in 2009. The histological subtypes of NHL fall into two major classes: indolent (slow growing) and aggressive (fast growing). Lymphomas with indolent histologies include B-cell follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and cutaneous T-cell lymphoma. Lymphomas with aggressive histologies include diffuse large B-cell lymphoma, lymphoblastic lymphoma, and Burkitt lymphoma. Mantle cell lymphoma is classified as an aggressive lymphoma but possesses characteristics of both indolent and aggressive disease.

Treatment of indolent NHL depends on the histology and stage of the disease. Because indolent NHL is often asymptomatic in early stages, it is generally advanced (stage III or IV) at the time of detection. Treatment for indolent NHL typically involves a combination of chemotherapy and immunotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab. Alternatively, other chemotherapy regimens may be used in combination with rituximab, including cyclophosphamide, vincristine, and prednisone and fludarabine-based regimens. Radiation and bone marrow or stem cell transplantation are treatment options in selected patients.

Indolent NHL is generally incurable. Patients typically follow a course of remission and relapse requiring multiple rounds of therapy with rituximab, chemotherapy, or both. Eventually, most patients become refractory to chemotherapeutic agents, rituximab, or both.[20] Therefore, new treatments are needed to prolong the duration of remission and overall survival for patients with relapsed and refractory indolent NHL.

Bendamustine is useful in that it shows little cross-reactivity with common first-line indolent NHL therapies. It is effective in patients refractory to rituximab, chemotherapy, or both...”

What about side effects?

“Bendamustine is generally well tolerated. The most common serious (grade 3 or 4) adverse events are hematologic in nature. Gastrointestinal events are also commonly observed but are usually mild to moderate in severity. Adverse events can often be managed with supportive therapies or dosage modifications.”

Translation: like other chemotherapy agents, it can throw your blood counts out of whack and it can make you vomit. Yet, they say these side effects can be pretty much kept under control with other drugs.

In the oncologist’s lexicon, “well tolerated” doesn’t mean you feel good. It means the doctors don’t usually have to cancel the chemotherapy because it’s making you so sick you can’t stand it.

In any event, this is another bit of encouraging news for me, for whenever it should happen that “watch and wait” ends and “go and do something” begins.

It’s good to have more than one arrow in the quiver, to be sure.

March 8, 2010 - Hope on the Horizon

The big medical conference each year in the field of lymphoma treatment is ASH – the American Society of Hematology. This year’s conference, I understand, contained good news for people like me with indolent lymphomas – particularly follicular lymphoma. Check out this video interview with Dr. Dr. Ephraim Hochberg, Director of Clinical Lymphoma Research at Dana-Farber/Massachusetts General Hospital:

An Expert's Perspective on the Latest in NHL from Patient Powerr on Vimeo.

It’s encouraging to hear this lymphoma researcher speak of turning the corner and heading into the home stretch on some long-term research efforts. The longer my lymphoma remains sluggish, the longer my watch-and-wait treatment approach continues, the more likely it becomes that some new medicine will be available when I need it.

September 25, 2009 - A Survivor's Testimony: Never Give Up

Here’s a video containing the testimony of Dr. Samuel Gruber, a longtime lymphoma survivor:

The Survivors Club - Doc Gruber - Lymphoma Survivor

There’s a lesson for us here about the importance of being our own advocate: of keeping up with the medical literature (as best we can, anyway), and talking with our doctors about the things we read.

There’s also a comforting truth in what Dr. Gruber says about the rapid pace of research in lymphoma treatments. The longer we hang on, the more new treatments will become available.

Reason for hope!

September 15, 2009 - Natural Born Killers

They’re calling it a “master switch” that can turn on the immune system’s ability to fight cancer.

Maybe that description’s overblown, or maybe it’s not, but British scientists have surely made a breakthrough by identifying a gene that stimulates the body’s production of NK, or “natural killer” cells, a type of white blood cell.

From an article describing the new development:

“Infusions of natural killer cells donated from volunteers are already given to some cancer patients. However, because they come from another person, they are not a complete match and so do not work as well.

The discovery of the 'master-switch' – a gene called E4bp4 that causes ‘blank’ stem cells to turn into natural killer cells – paves the way for a drug to boost the patient’s own stock of the cells.

(Natural killer cells, highlighted in red, in the spleen of a virus-infected mouse. To find where this picture came from, click here.)

Researcher Hugh Brady, of Imperial College London, said: ‘The natural killer cell was like the Cinderella of the white blood cells, we didn’t know very much about them.

We knew a little bit about how they work but we didn’t know where they came from.

We stumbled on this when researching childhood leukaemia. We thought the gene was involved in that. It turns it probably isn’t but it has a very important role in the immune system.

With a bit of serendipity we have found the key to the pathway that gives rise to natural killer cells.’”

A lot more research is needed, says Dr. Brady, before any medication that stimulates natural-killer cell growth is ready for prime time. Scientists aren’t even 100% sure that NK cells always have a beneficial function:

“Now finally, we will be able to find out if the progression of these diseases is impeded or aided by the removal of natural killer cells from the equation.

This will solve the often-debated question of whether NK cells are always the ‘good guys’, or if in certain circumstances they cause more harm than good.’”

Good guys? Bad guys? It’s a cell-eat-cell world out there in the microscopic regions of the human body, it would seem.

Let’s just hope the scientists are onto a whole lot of new good guys with this one.

August 11, 2009 - Bring On Those Nanobees

There’s a widespread news story in the past couple days about “nanobees” – a technique of cancer treatment involving nanoparticles that head right for tumor cells. Researchers at Washington University in St. Louis have armed these tiny particles with melittin, a protein that’s the active ingredient in bee venom.

It’s a colorful image: swarms of nanoparticles racing through the body, locating cancer cells and stinging them to death. The fact that these particles are armed with a chemical found in actual bee venom verges on the poetic.

Here’s Paul Schlesinger, one of the researchers, commenting on why melittin shows such promise as an anti-cancer agent:

“Melittin has been of interest to researchers because in high enough concentration it can destroy any cell it comes into contact with, making it an effective antibacterial and antifungal agent and potentially an anticancer agent. Cancer cells can adapt and develop resistance to many anticancer agents that alter gene function or target a cell’s DNA, but it’s hard for cells to find a way around the mechanism that melittin uses to kill.”

So far, the researchers have had success in killing human tumor cells that have been implanted in mice. The nanobees have done their job on the tumors, delivering the melittin without causing ill effects in the mice.

This is important because, if melittin were injected directly into the bloodstream, it would attack hemoglobin cells. Somehow, when this protein hitches a ride on a nanoparticle, it holds off on its venomous attack until the nanoparticle delivers it to a cancer cell.

Yes, there’s a lot of lab work involved in developing a treatment like this. I find it interesting, though, that the new therapy’s essential ingredient is something found in nature – in the humble honeybee.

Whatever actual treatments may emerge from this new approach, it’s comforting to think that the answer was out there in nature, all along.

July 22, 2009 - Dulanermin

Paging through an old copy of Cure magazine (a publication for cancer survivors), I notice a headline in a full-page ad: “Have you been diagnosed with Follicular Non-Hodgkin’s Lymphoma (NHL) following previous rituximab therapy?”

“That’s me,” says I to myself.

Reading on, I discover it’s an ad for a clinical trial being conducted by Genentech – the drug company that brought us rituximab (Rituxan). They’re also the people who flew Claire and me to Las Vegas a few years ago, to give a little motivational talk to their sales force.

Down at the bottom is a serial number I can use at the clinicaltrials.gov website, to find out more about this study.

I visit that site, key in the number, and come up with a page describing a study of a new investigational drug called Apo2L/TRAIL – trade name, Dulanermin.

It’s a Phase II clinical trial – which means it’s still in the early stages of investigation. As of now, the trial is also fully subscribed: which may be just as well, since I’m not sure I’d want to risk the side effects of a Phase II trial when I’m still in a watch-and-wait mode and feeling good.

It’s interesting to read about this new drug, all the same, because it could be in my future.

Here’s the scoop, from an Amgen press release of a couple months ago (the Amgen pharmaceutical company is conducting this research in partnership with Genentech). Dulanermin is one of a family of “highly selective therapies to induce cancer cell death.” Well, who can argue with that?

“In cancer,” the article continues, “the dysregulation of apoptosis is critical in the development and survival of tumors.” I know, from previous reading, that apoptosis is cell death – the normal tendency of cells to die according to a genetically-preset timetable, only to be replaced by new cells. In cancer cells, the apoptosis switch is turned off, allowing them to continue to grow and wreak havoc in the body. “The dysregulation of apoptosis” is inscrutable medical jargon for “throwing a wrench into the genetic machinery that would otherwise cause cells to die when they reach the end of their natural lifespan.”

Dulanermin – if it fulfills the hopes of the pharmaceutical researchers – would yank that monkey-wrench back out of the machinery, so cells would continue to die according to their normal timetable and would never morph into cancer cells.

The article defines dulanermin as “a recombinant human protein that targets death receptors 4 and 5.” Sounds like something out of Star Wars: “Luke, your mission is to fly your X-fighter along the surface of the Death Star and take out death receptors 4 and 5. May the Force be with you.”

Go for it, Luke.

Is this the next Rituxan? Impossible to say. Clinical trials like this are being conducted all the time, mostly below the radar of non-medical types like me. Every once in a while, a full-page ad jumps out at us, a reminder that this valuable work is going on.

Kudos to the researchers for keeping up with this sort of thing.

Who knows? If this one ever makes it to a Phase III trial, maybe they can sign me up.

June 14, 2009 - New Lymphoma Vaccine

I’m feeling hopeful, today, after reading some articles about a new vaccine for follicular lymphoma, recently announced by Dr. Stephen Schuster, of the University of Pennsylvania’s Abramson Cancer Center, at the American Society of Clinical Oncology’s annual meeting in Orlando. One article is a University of Pennsylvania press release, the other an ABC News story.

Dr. Schuster’s study involves a personalized cancer vaccine, fabricated out of the patient’s own malignant cells. Other cancer vaccines are created to go after some factor that influences the survival of cancer cells. This one is different, Dr. Schuster says, because it goes after the cancer itself. The vaccine – or, rather, the process of producing it, since every patient’s version is different – is called BiovaxID.

I suppose it’s kind of like giving a bloodhound an article of clothing belonging to the fugitive being tracked. Having memorized the criminal’s distinctive scent, the hound is able to sniff out the quarry. The cancer vaccine, equipped with chemical markers from the patient’s malignant cells, does much the same thing.

The vaccines, which take 3 months to produce, are given in 5 injections spaced over 6 months.

The vaccine was given to follicular lymphoma patients who had received the standard CHOP chemotherapy treatment (the same one I had, minus the Rituxan), and who had gone into a remission lasting longer than 6 months (mine lasted 8 months). Those patients in the trial who received BiovaxID did significantly better than those in the control group: 44.2 months without a relapse, on the average, for those in the vaccine group, as compared with 30.6 months for those in the control group.

Dr. Schuster is calling for a new clinical trial, to see how the results will come out for those treated with R-CHOP (CHOP + Rituxan), as I was.

I wonder how long it will be before the vaccine is available, outside of clinical trials. I wonder, also, to which patients it would be given: whether only to people like those in the clinical trial, who are still in remission after treatment, or to people like me as well, who are out of remission. (Then again, maybe it could help me after my watching and waiting time is over, and some other treatment puts me back into remission.)

Complicated questions, to be sure. Regardless, news like this is always a source of hope.

May 7, 2009 - Microscope-Ready

Good news, today, in the form of a news article about government allocations for medical research. The article in Bloomberg News reports on what one researcher calls “a stunningly large number” of dollars – $10.4 billion of ‘em, to be exact – that will be devoted to curing what ails us. “Breakthrough findings on obesity, AIDS, Alzheimer’s, Parkinson’s and cancer” are on the way, the article predicts.

President Obama has included this amount as part of his $787 billion shot in the arm for the economy. There’s been lots of talk about rebuilding the nation’s crumbling infrastructure through “shovel-ready” projects like bridges and highways. It’s nice to know there are some microscope-ready projects, as well, to benefit those of us with chronic illnesses.

There are some who say that, once you have cancer, never a day goes by that you don’t think about the disease, at least once. I’m pretty sure that’s continued to be true for me, during this extended period of watch-and-wait. Some days I think about it a lot, other days it’s no more than a fleeting thought. Yet the though is always there, if only lurking below the surface.

I would a great thing, indeed, if I didn’t have to think about it anymore.

It would be a great thing, as well, if some additional billions would be used to buy health insurance for those without it – although I suppose that’s coming down the pike soon enough, along with the rest of the President’s healthcare-funding proposal.

Why is this important? Check out this 7-minute video that tells what an impossible fix a hard-working American family can get into when cancer comes knocking at the door:



Quite apart from the humanitarian factor, cleaning up our nation’s broken healthcare-funding system – that leaks dollars like a sieve – will actually strengthen the economy.

Now, that’s the sort of win-win scenario that even a fiscal conservative ought to be able to appreciate.

April 25, 2009 - Take a Little Wine

“No longer drink only water, but take a little wine for the sake of your stomach and your frequent ailments.” So says 1 Timothy 5:23 – a little practical advice, in the midst of some miscellaneous exhortations at the end of this New Testament letter.

Who woulda thunk it? Who could imagine this homey, first-century medical advice would surface at a 21st Century cancer research conference?

It has, though – at least, according to a recently-released research study. From a news article describing it:

“Pre-diagnostic wine consumption may reduce the risk of death and relapse among non-Hodgkin's lymphoma patients, according to an epidemiology study presented at the American Association for Cancer Research 100th Annual Meeting 2009.... [The researchers] analyzed data about 546 women with non-Hodgkin's lymphoma. They found that those who drank wine had a 76 percent five-year survival compared with 68 percent for non-wine drinkers. Further research found five-year, disease-free survival was 70 percent among those who drank wine compared with 65 percent among non-wine drinkers.” (“Drinking Wine May Increase Survival Among Non-Hodgkin's Lymphoma Patients,” ScienceDaily, April 24, 2009.)

Admittedly, those numbers aren’t all that startling. The wine-bibbers get a mild statistical bump, that’s all. Draining Bacchus’ cup is clearly no panacea, but it does seem that “a little wine,” as the author of 1 Timothy advises, can be good for what ails ya.

Not every tippler will be happy with the study’s results, though: “Beer and/or liquor consumption did not show a benefit,” the report soberly concludes.

It’s just the vino, folks.

According to the article, wine has certain anti-oxidants that tend to retard tumor growth. This is consistent with some earlier studies that show wine (especially red wine) has a mild positive effect on heart health. An occasional glass of Chianti or Lambrusco is part of the highly-touted “Mediterranean diet.” Now, it appears the fruit of the vine does a little something for lymphoma prevention as well.

The oncologists aren’t exactly advocating pub crawls. Far from it: “This conclusion is controversial, because excessive drinking has a negative social and health impact, and it is difficult to define what is moderate and what is excessive,” says one of the lead researchers, by way of a disclaimer.

(Nota bene: 1 Timothy does specify “a little wine.” All things in moderation.)

I’ve always thought an occasional glass of red wine to be one of life’s little pleasures. It’s nice when something that tastes so good turns out to be good for you, as well.

Wine has even found its way into religious poetry on occasion. I close with these lines from the medieval Persian poet, Rumi:

“The grapes of my body can only become wine
After the winemaker tramples me.
I surrender my spirit like grapes to his trampling
So my inmost heart can blaze and dance with joy.
Although the grapes go on weeping blood and sobbing
‘I cannot bear any more anguish, any more cruelty’
The trampler stuffs cotton in his ears: ‘I am not working in ignorance
You can deny me if you want, you have every excuse,
But it is I who am the Master of this Work.
And when through my Passion you reach Perfection,
You will never be done praising my name.’”

– Mevlana Jelaluddin Rumi (1207 - 1273)

Salut!

March 21, 2009 - Let's Hear It for L19!

Here’s a very encouraging article about an exciting new approach in B-cell non-Hodgkin lymphoma treatment. Thanks to Dr. Wendy Harpham for sending me the link.

Swiss researchers have found a way to use a human antibody called L19 to recognize and target newly-formed blood vessels that occur in tumor tissue.

The team of researchers, led by Dr. Dario Neri, used rituximab (the same monoclonal antibody I received along with my CHOP chemotherapy) in conjunction with L19. From the article:

“The success of the Neri team’s new therapeutic approach relies on the ability of the immunocytokine L19-IL2 to attract and activate certain white blood cells, including the so-called natural killer cells, towards the tumor, thus potentiating the therapeutic activity of rituximab.”

Early trials using the new approach with mice were encouraging, then the scientists were able to replicate those results in humans. In the before-and-after PET scan images below, all the black spots, indicating active lymphoma, disappeared following treatment (the remaining dark areas in the right-hand photos are the brain, heart and bladder that always show up dark in PET scans):

Now, the researchers are moving on to develop the treatment for more widespread use. New medications using L19 are in phase I and II clinical trials, according to the article.

Yes, indeed - there are good things coming down the research pipeline!

March 9, 2009 - More Questions About Maintenance Rituxan

Steve, a reader of this blog, reminded me of a 2006 European study that found “dramatic” results in follicular NHL patients who were receiving maintenance Rituxan treatments. Unlike the one I cited yesterday, this study includes patients who have received R-CHOP.

Those patients in the study who received R-CHOP, and who subsequently received maintenance Rituxan, experienced an average of 52 months without their disease progressing – as opposed to 23 months in the control group. That’s more than double the time.

That raises a lot of questions for me. My disease has already returned, but it’s not doing much of anything. Every time I go for a scan, the verdict is, “Still there, but no bigger.” Dr. Lerner has me on “watch and wait,” the reasons being that (1) my slightly enlarged, malignant lymph nodes are doing no immediate harm, and (2) when they get large enough to treat, there’s a high likelihood that a second round of chemo will put me back into remission (and, if I receive a stem-cell transplant instead, there’s even the possibility of a cure).

I don’t know whether starting on Rituxan-only treatments is still an option for me, at this stage – everyone in the research studies presumably began receiving them right after their chemo. Even if maintenance Rituxan is still available to me (and if we could convince the insurance company to fund it), I’m still not sure it’s the best idea. Dr. Lerner’s cool-under-fire strategy of waiting till we see the whites of their eyes before we start blasting away appeals to me.

Questions, questions. What if? When? Why? Why not? You never get away from the questions, when you’re a cancer survivor.

“Wait for the Lord;
be strong, and let your heart take courage;
wait for the Lord!”

– Psalm 27:14

March 8, 2009 - The Treatment I Didn't Get

Today I run across a Reuters news article about rituximab (trade name, Rituxan), the monoclonal antibody drug I received along with my chemotherapy. It seems a research study has just demonstrated good results for “maintenance therapy” with Rituxan – in other words, continuing treatment with the drug over time, even after the cancer has gone into remission:

“An improved disease response was seen in 22% of rituximab-treated patients versus just 7% of control subjects....

Three-year progression-free survival was also higher in the rituximab group: 68% vs. 33% in controls. In the subgroup of 282 patients with follicular lymphoma, the corresponding rates were 64% and 33%. Higher overall survival rates were seen in the rituximab group as well, although the differences fell short of statistical significance....

‘Observations from this study inform the design of future studies and add to a substantial body of evidence that the combination of rituximab with chemotherapy is a new standard for patients with indolent lymphoma who require treatment,’ the authors conclude.”

At the time my R-CHOP chemotherapy ended (the “R” in R-CHOP stands for Rituxan), I was aware that some patients were continuing to receive monthly treatments with Rituxan for a year or more, as a preventative measure. This was, and continues to be, somewhat controversial. At several NHL patients’ conferences I attended, the medical experts making the speeches said the jury was still out on whether or not maintenance Rituxan does any good. With the tremendously high cost of this medication, many medical insurers had labeled it “experimental,” and were not funding its use in maintenance treatment. (I never took the matter up with my insurance people, because Dr. Lerner didn’t recommend maintenance Rituxan in my case.)

Well, now the jury has filed back into the courtroom and delivered their verdict: maintenance Rituxan does work – at least for indolent NHL patients who have had the CVP chemo regimen (cyclophosphamide, vincristine and prednisone). The researchers didn’t focus on patients who’ve had the CHOP chemo cocktail, rather than CVP – although, since vincristine and prednisone are two out of the four drugs in CHOP, I would think there’s a pretty good chance maintenance Rituxan would have improved my long-term prognosis, as well.

This raises a lot of unanswered – and probably unanswerable – questions for me. Chief among them is, if I had received maintenance Rituxan, would my remission have lasted longer than it did?

Hindsight, as they say, is 20/20. I’m not going to run off and ask Dr. Lerner about maintenance Rituxan now, but it does give me something to think about. Maybe I'll ask him what he thinks of this article, next time I see him...

March 7, 2009 - A Cure for Cancer? Not.

“We’ve launched a new effort to find a cure for cancer in our time.” Those were President Obama’s words at Thursday’s Healthcare Summit in Washington.

A few days earlier, he said much the same thing in his address to Congress.

This sort of promise by a politician is not new. Richard Nixon proclaimed as much, back in 1971. It’s stirring rhetoric, and I certainly applaud the intentions behind it, but the promise is very likely impossible to fulfill.

The reason? Cancer isn’t just one disease. All the experts are saying there’s no magic bullet, no wonder drug like the Salk polio vaccine, that will suddenly send the nation’s oncologists scrambling to find a new medical specialty.

Cancer is dozens of diseases, maybe even hundreds. Yes, it’s characterized by the tendency of certain cells to grow uncontrollably, rather than shuffling off to die (as their genetic programming would ordinarily direct them to do). Yet, the causes of this cellular misbehavior are legion. It’s highly unlikely that a single, miracle cure is out there, waiting for some enterprising researcher to uncover it. Why, it’s even unlikely there could be a single cure for non-Hodgkin lymphoma – which, by all accounts, is a family of dozens of different diseases.

That’s no reason to stop trying, of course. Surely, there are cancer cures waiting to be discovered, through even modest increases in research funding. If the political slogan, “finding a cure for cancer,” is what it takes to build support for this cause, I’m surely not going to stand in the way.

So, Mr. President: when it comes to rallying Americans to support the cause of healthcare reform, particularly increased funding for cancer research, I say, “Go for it!” Yet, when you hold out the dazzling prospect of a single cure for cancer, I’ll consider that more of a rhetorical flourish than a statement firmly grounded in medical fact.

January 2, 2009 - Hope Begins in the Dark

It’s a new year. Most of us are very glad to leave 2008 behind, with all the economic turmoil of recent months. May we have much better news in 2009!

There’s some encouraging news already on the cancer research front. A researcher at Cornell University named Michael King has developed something he calls a “lint brush” for the blood – “a tiny, implantable device that captures and kills cancer cells in the bloodstream before they spread through the body.”

This tiny, tubelike device contains a special protein called “selectin” on its inside surface. As blood cells flow through the tube, free-floating cancer cells bond to the selectin and are held there, so they can do no harm. Early test results indicate that about 30% of cancer molecules stick to the selectin on each pass. Since our blood circulates through the body constantly, this means that just one of these devices can eventually filter the body’s entire blood supply. Each repeated pass results in more cancer cells being corralled on the surface of the tube. Then, a second protein is released, causing the cancer cells to die.

I wonder if this device could work in the vessels of the lymphatic system, just as they do in the bloodstream?

Another article tells how scientists are scanning the ocean floor to discover new compounds that can be developed into anti-cancer drugs. The University of California at Santa Cruz has a set-up whereby sea-floor sediment is piped into special, chemical-scanning robots, that analyze them for compounds that could be useful to the pharmaceutical industry.

From the article:

“In its first year of operation, the lab has already had two interesting hits. One, the as-yet-unnamed product of a rod-shaped marine bacterium, is 98 percent efficient at killing the parasite that causes African sleeping sickness, a fatal disease common in sub-Saharan Africa. The other, dubbed ‘tamoxilog,’ is biologically similar to tamoxifen, a drug commonly used to treat breast cancer, though preliminary tests suggest tamoxilog is twice as powerful.”



Maybe the next big lymphoma drug is at the bottom of the sea, waiting to be discovered. Stranger things have happened.

Christian essayist Anne Lamott has written: “Hope begins in the dark, the stubborn hope that if you just show up and try to do the right thing, the dawn will come. You wait and watch and work: you don’t give up.”

I doubt if Anne was thinking about the inky darkness of the ocean floor when she wrote that. Her words are oddly appropriate, though: for this is surely a story of hope that begins in the dark.

November 7, 2008 - Sequencing the Cancer Genome

All but buried by the profusion of political articles in yesterday’s newspaper was an article about a remarkable break- through in cancer research.


Working with the genes of a woman in her 50s who died of leukemia (AML), scientists at Washington University in St. Louis have sequenced the entire genome of cancer cells taken from her bone marrow, and have compared it to the genome of her healthy skin cells. This was the first time this has ever been done as a method of cancer research.

The comparative study revealed 10 separate genetic mutations present in the woman’s cancer cells, that likely had some impact on her disease: either causing her cancer or affecting her response to treatment. In an elaborate number-crunching exercise, the scientists picked these mutations out from among the 20,000 or so genes that make up the human genome. (By contrast, previous studies have searched for mutations only among 100 or so genes scientists have suspected could be involved.)

As the New York Times reports, it was a technically daunting task:

“The new research, by looking at the entire genome – all the DNA – and aiming to find all the mutations involved in a particular cancer, differs markedly from earlier studies, which have searched fewer genes for individual mutations. The project, which took months and cost $1 million, was made possible by recent advances in technology that have made it easier and cheaper to analyze 100 million DNA snippets than it used to be to analyze 100.”

This is gee-whiz technical wizardry, but – more importantly – it holds out real hope for cancer research in general. With these powerful new tools at their disposal, researchers will be able to isolate and focus in on genetic mutations that are of interest. They can then identify hitherto-unknown causes of that particular type or cancer, or create therapies to successfully defeat it.

As this technique is used to study more cancer patients, comparisons will be made between one person and another. This is expected to reveal a number of mutations that are unique to each individual, some of which could be used to create “designer drugs” to help them recover. Eventually, though – and far more exciting – a few mutations will likely turn up that are common to all patients with that type of cancer.

That is the holy grail of cancer research: a single mutation that’s responsible for causing that type of cancer. In the words of Washington University researcher Richard K. Wilson:

“Ultimately, one signal tells the cell to grow, grow, grow. There has to be something in common. It’s that commonality we’ll find that will tell us what treatment will be the most powerful.”

Exciting stuff, indeed. A reason for hope!

October 8, 2008 - Better Living Through Web Crawling

There have been lots of technological developments in recent years that have revolutionized cancer treatment. One of the most revolutionary of all, though, is a change whose impact is indirect, even as it is massive.

You’re participating in it right now, as you read these words. It’s the Internet.

A September 29th article in the New York Times highlights the many different ways patients deal with this vast ocean of medical information at their fingertips:

“Information gives some people a sense of control. For others, it’s overwhelming. An acquaintance of this reporter, a New York father coping with his infant son’s heart problem, knew he would be paralyzed with indecision if his research led to too many choices. So he focused on finding the area’s best pediatric cardiologist and left the decisions to the experts.

Others, like Amy Haberland, 50, a breast cancer patient in Arlington, Mass., pore through medical journals, looking not just for answers but also for better questions to ask their doctors.

‘Knowledge is power,’ Ms. Haberland said. ‘I think knowing the reality of the risks of my cancer makes me more comfortable undergoing my treatment.’” (Tara Parker-Pope, “You’re Sick. Now What? Knowledge Is Power,” New York Times, September 29, 2008)

My personality type is obviously closer to the second of these two patients than to the first. One of the first things I did, even before my diagnosis was definite, was to high-tail it to library. What I couldn’t find on the library shelves, I began searching for – voraciously – on the internet. Before long, I had a basic knowledge of lymphoma and the underlying biological systems that are affected by it. My doctors know vastly more than I, of course – I never pretend otherwise – but at least we’re able to converse together with some degree of mutual understanding.

Not everyone’s like this. I know some fellow patients who put themselves, wholly and completely into their doctor’s hands, saying, “Please don’t overwhelm me with details, Doc. I trust you, and I trust you to tell me what I need to know about my condition.”

There’s no right or wrong here. It’s a matter of style.

Vive la difference.

September 9, 2008 - Cancer Misinformation

OK, here’s a curious news item. Someone’s done a study of misinformation about cancer, and how spurious beliefs vary according to whether a person lives in the industrialized or the developing world:

“Researchers interviewed 29,925 people in 29 countries last year to compare data on perceptions about cancer risk factors among high-, middle-, and low-income countries.

Among their findings was the fact that people in high-income countries were least likely to believe that drinking alcohol increases the risk of cancer, when, in fact, cancer risk rises as alcohol intake increases. Specifically, 42 percent of the people in the high-income countries said alcohol does not increase the risk, compared with 26 percent of those in middle-income countries and 15 percent of those in low-income countries.”

So, first-world people insist on believing, despite the evidence, that they can tipple risk-free. They also choose to believe – again, contrary to evidence – that eating a diet high in fruits and vegetables will do more to lower their cancer risk than abstaining from alcohol. It won’t. Alcohol is a far bigger risk.

First-world people also believe exposure to air pollution is more carcinogenic than drinking. It’s not.

People in middle- and low-income countries tend to take a Que Sera, Sera attitude towards cancer, believing not much can be done to treat it. Folks in wealthier countries – evidently more used to seeing baldheaded cancer survivors walking around – believe that aggressive therapy can make a difference.

Generally speaking, “people in all countries were more ready to accept that things they could not control (e.g., air pollution) were risk factors than things they could control (e.g., overweight, which is an established cancer risk factor).”

I’m still processing these observations. I don’t quite know what to make of them. Of course, it’s humbling to be reminded, once again, of how cancer treatment is pretty much the preserve of the wealthy (with “wealthy” defined according to a global standard, to include pretty much everyone in Europe and North America). In many parts of the two-thirds world, a cancer diagnosis is still pretty much a death sentence.

Yet, from Basel to Bangladesh, there’s still a lot of unreasoning fear out there when it comes to cancer. It’s a better fit for our frame of reference, somehow, to see cancer as an unstoppable force that descends with devastating randomness (caused by something like air pollution that few of us can do anything to prevent), rather than as something that can be a consequence of our own lifestyle choices.

Cancer is a great drive-in movie screen, on which we tend to project our desires as well as our fears. No wonder it can be such a hard subject to talk about.

September 3, 2008 - Another New Cocktail

No, I’m not talking about some concoction served in an umbrella glass, under a buzzing neon light. I’m talking about a new combination of anti-cancer drugs that may help certain lymphoma patients.

“Novel Clinical Study For Lymphoma Patients Beginning,” reads the headline of yesterday’s internet news article. It heralds a clinical study, investigating whether patients receiving a new combination of two chemotherapy drugs will do better than those receiving more conventional treatments. The drugs are for patients with diffuse large B-cell or mantle-cell lymphoma. Diffuse large B-cell was the aggressive type of cancer I had, which has (fortunately) not come back since my R-CHOP chemo treatments in the spring of 2006. If it ever comes back, I could potentially benefit from tossing back a few of these new cocktails (well, not literally tossing them back; they’d be delivered through IV tubes).

The drugs being studied are bortezomib, marketed as Velcade, and vorinostat, marketed as Zolinza. (Where DO they come up with these crazy names?) Bortezomib – a comparative old-timer in the world of cancer drugs – has been around since 1995, and vorinostat is a newer drug, approved by the FDA for treatment of another type of lymphoma (cutaneous T-cell) less than two years ago.

These types of clinical trials go on all the time. This one’s a phase II trial, one of the riskier varieties. As I understand it, phase I trials are truly experimental – only the sickest patients get these drugs, the unfortunate souls for whom nothing else is working. Based on experiments with laboratory animals (the proverbial “guinea pigs,” whether or not they actually belong to that species), the scientists are reasonably sure the drug will help humans, but they can’t be absolutely sure. So, they pick a few people who have no other choices, give them the new drug, then sit back and watch what happens.

If the experimental subjects do better than expected, the scientists move on to phase II. They’re still working with a relatively small group of desperately ill patients, but this time they’re trying to figure out the dosage. In this stage, patients sometimes experience severe side effects, as the experts try to get the dosage right. Neither phase I nor phase II trials are a walk in the park for the volunteers who participate in them – although they’re usually willing enough to take the risk, because they have few other alternatives.

If the signs continue to be good, the researchers move on to a stage III trial. By now, they know the drug works, but they need hard data comparing it to other drugs. This is the sort of trial that involves thousands of patients all over the country (or even the world). It includes randomization – there is a randomly-selected control group of patients, who are given some other, more established drug instead of the one being studied. (In cancer trials, placebos are rarely given to the control group, for ethical reasons.)

If the new drug makes it through this third gate, it will probably receive FDA approval. The company then dispatches its eager sales force out to doctors’ offices, with their free pens and sandwich trays for the office staff. After the drug is out there for a little while, stage IV trials follow, as the benefits and side-effects of the treatment protocols are studied further, over time.

Speaking as a cancer survivor, it’s encouraging to read of new developments like these. I’m glad the pharmaceutical researchers are out there, dripping fluids from eyedroppers into petri dishes, or whatever they do. It’s a long road, from the genesis of an idea in a laboratory to a chemo nurse hanging a bag of the stuff on an IV pole. Drug companies have to put up millions of bucks before they see a penny of profits, and for every drug that makes it into production, many more die on the vine, never making it out of stages I or II.

Will I ever receive this yet-unnamed drug combo? Who’s to say? It just goes to show how dynamic and uncertain the field of cancer treatment continues to be. I’m in a slow, watch-and-wait mode right now. It’s remarkable – and scary – to think that the drug that could help me one day may still be in the early theoretical stages, years away from production.

We live with that uncertainty, and with that hope.

July 21, 2008 - Triple-Barreled Shotgun

A news release from the Leukemia and Lymphoma Society directed me to an article in The Oncologist, which includes this conclusion:

“Treatment options for patients with follicular lymphoma have significantly expanded. They include ‘wait and watch,’ radiotherapy alone for stage 1 or 2, rituximab alone, RIT alone, single- or multiple-agent chemotherapy combined with rituximab, and participation in many ongoing studies with a variety of different treatment combinations and intensity levels. Therapy might thus ultimately be adapted to the patient’s individual situation, depending on the aggressiveness of the particular patient’s disease while still relying on a continuously growing repertoire of salvage therapies.

Multiple studies in NHL indicate that chemotherapy combined with rituximab or RIT yields superior results compared with chemotherapy alone. We argue that chemotherapy combined with both RIT and full-dose biological treatment has an even higher efficacy potential. The tripletherapy approach employing upfront chemotherapy combined with optimized RIT and extended biologic treatment with antibodies may represent the best chance for prolonged disease-free survival, and potential cure, keeping in reserve the possibility of intensification with ASCT or allografting for relapsed patients.”

(Franz Buchegger, Oliver W. Press, Angelika Bischof Delaloye and Nicolas Ketterer, “Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma,” The Oncologist, 2008;13:657–667.)

I plowed through the whole article, dense medical jargon and all, because it could very well describe the course of my next treatment.

Of the various treatment options described in the second sentence, I’ve already had “multiple-agent chemotherapy combined with rituximab” (the R-CHOP chemo cocktail I received in January-May, 2006). Ever since my relapse last spring or summer, my current “treatment” (if it can be called that) has been “wait and watch.”

I’ve known for some time about three other treatment options: autologous stem-cell transplant (ASCT), “extended” or maintenance treatment with rituximab, and radioimmunotherapy (RIT). RIT refers to one of two drugs, Bexxar and Zevalin, each of which attaches a radioactive tag to rituximab molecules, allowing tiny particles of radioactive material to piggyback on rituximab’s unerring ability to find and travel to lymphoma cells.

RIT is the treatment that came close to disappearing at the end of last year, when revised Medicare reimbursement guidelines threatened to price it out of existence (see my November 14 and November 30, 2007 blog entries). After a deluge of letters from cancer patients and their friends, Congress swooped in at the last minute and granted a temporary extension of the old reimbursement guidelines. Recently, the same thing nearly happened again. The President vetoed the latest Medicare bill that included sufficient funding to keep RIT alive, but Congress overrode his veto.

What’s new about this article is that it’s recommending that a triple combination of therapies – chemo, maintenance rituximab treatment and RIT – be undertaken before a relapsed NHL patient goes for a stem-cell transplant. Because of the dangers associated with stem-cell transplants, this new thinking pushes that option a little lower down the priority list.

My former treatment was like a double-barreled shotgun: go after the cancer with both barrels at once. Reserved for the future were two other promising possibilities: RIT (with or without a follow-up program of maintenance rituximab) and stem-cell transplant. There was also, of course, the possibility of simply reloading the shotgun and firing the same two barrels again (rituximab combined with a different chemo cocktail – since CHOP cannot be repeated). Now, the authors of this article are recommending that a third barrel be added to the shotgun, blasting the cancer with all three at once: chemo, RIT and maintenance rituximab.

I wonder if this will become the new standard for treating relapsed follicular lymphoma? Or, if it will simply be one strategy out there, that continues to be debated?

I wonder, also, what the insurance companies will think of the new triple-barreled combination? It will surely be more expensive (although probably still not as pricey as a stem-cell transplant).

Last week I received a phone call from Dr. Lerner, letting me know that my July 1st CT scan indicated only slight growth in my abdominal mass. How slight? Two millimeters is what the doctor said – explaining that the growth is so small, some would consider it to be within the margin of error. Dr. Lerner confirmed that, when I meet with him in early August, continued watch-and-wait will be his recommendation.

I think I’ll ask him what he thinks of the triple-barreled approach – just as a matter of interest. In any event, the slow pace at which my disease is progressing suggests it may be some considerable time before we’ll have to make any treatment decisions.

This is, of course, a good thing. By then, the “continuously growing repertoire of salvage therapies” may well have grown a little more, and that the ongoing debate about treatment options will have advanced that much further.