July 12, 2017 — A Living Drug

A hopeful news bulletin today from the New York Times:

“A Food and Drug Administration panel opened a new era in medicine on Wednesday, unanimously recommending that the agency approve the first treatment that genetically alters a patient’s own cells to fight leukemia, transforming them into what scientists call ‘a living drug’ that powerfully bolsters the immune system to shut down the disease.

If the F.D.A. accepts the recommendation, which is likely, the treatment will be the first gene therapy to reach the market. Others are expected...”

This particular treatment focuses on an uncommon form of childhood leukemia, and is earmarked for the 15% of patients who don’t respond to other treatments. Here’s how it works:

“The treatment requires removing millions of a patient’s T-cells — a type of white blood cell — and genetically engineering them to kill cancer cells. The technique employs a disabled form of H.I.V., the virus that causes AIDS, to carry new genetic material into the T-cells to reprogram them. The process turbocharges the T-cells to attack B-cells, a normal part of the immune system that turn malignant in leukemia. The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells.

The altered T-cells — called chimeric antigen receptor cells — are then dripped back into the patient’s veins, where they multiply and start fighting the cancer. Dr. Carl H. June, a leader of the University of Pennsylvania team that developed the treatment, calls the turbocharged cells ‘serial killers.’ A single one can destroy up to 100,000 cancer cells.”

It's fascinating to me that the new treatment uses a stripped-down form of the HIV virus as a pack-mule to carry the re-engineered genetic material back into the patient's cells. There's a kind of poetic justice in using one killer to fight another.

Although the article refers to this treatment as a “drug,” it stretches the usual definition of the word. It’s part drug, part treatment protocol.

Whatever it is, I’m glad to see it’s ready for prime time. It can’t be long before other, similar treatments for a variety of cancers will follow.

April 19, 2015 — Blood Test for Cancer?

This is huge.

Today’s New York Times tells of some research now under way that could lead to a simple blood test that could be used to diagnose cancer, particularly blood cancers like lymphoma (Gina Kolata, “Blood Test Shows Promise as Alternative to Cancer Biopsy,” New York Times, April 19, 2015)

From the article:

“The hope is that a simple blood draw — far less onerous for patients than a traditional biopsy or a CT scan — will enable oncologists to quickly figure out whether a treatment is working and, if it is, to continue monitoring the treatment in case the cancer develops resistance....

‘This could change forever the way we follow up not only response to treatments but also the emergence of resistance, and down the line could even be used for really early diagnosis,’ said Dr. José Baselga, physician in chief and chief medical officer at Memorial Sloan Kettering Cancer Center....

A National Cancer Institute study published this month in The Lancet Oncology, involving 126 patients with the most common form of lymphoma, found the test predicted recurrences more than three months before they were noticeable on CT scans.”

The new test follows a novel approach: searching for tiny snippets of cancer DNA that the body sheds into the bloodstream. The DNA shards are tiny and short-lived (they last for only a few hours), but extremely sophisticated blood tests are evidently now able to pick out this particular needle-in-a-haystack.

Early signs are that the test may be more useful for follow-up with existing patients who are known to have had tumors than for first-time diagnoses. It doesn’t appear to be the sort of test that could successfully be given as a routine screening for healthy patients:

“Another possible application — early diagnosis of cancer — is trickier. If a blood test showed cancer DNA, what would that mean? Where is the tumor, and would it help to find and treat it early? Some cancers stop growing and even go away on their own. With others, the outcome is just as good if the cancer is found later.”

If this blood test is successfully developed for clinical use, it could greatly reduce the need for CT and PET scans in monitoring patients during and after treatment.

As I’ve said, this is huge (although, admittedly, still just a theory at this point). I’ll be watching for further news on this.

August 9, 2014 - A Promising Discovery

"I have seen the future of cancer treatment, and its name is... Silvestrol?”

I’m not qualified to make such a claim, of course, but maybe some knowledgeable researchers who are would go so far as to say such a thing. There’s a bit of hyperbole in that statement, but it’s an eye-catching way to point out a new discovery that could be a really significant development in the long term, for blood-cancer patients.

According to an article the Leukemia and Lymphoma Society has been sending around, Silvestrol is a compound derived from “a plant called Aglaia foveolata, which is native to Indonesia, Brunei, and Malaysia.”

Rather than attacking a certain well-known cancer-causing gene, this stuff prevents it from being produced at all.

The tree is an endangered species, whose habitat is threatened by development.

An older article, chronicling the substance’s discovery, is here.

This reminds me of a movie that came out a while back, Medicine Man (1992), starring Sean Connery and Lorraine Bracco. Two courageous botanists fight off developers, whose bulldozers are about to ravage a section of Amazonian rain forest where a promising cancer drug has just been discovered. They bicker then fall in love, of course. (Hey, it's Hollywood, what do you expect?)

There’s more on the website of Memorial Sloan-Kettering (which is where Silvestrol’s treatment potential is being investigated)). “Blocking the production of key cancer genes is a completely new way of treating cancer,” says Dr. Hans-Guido Wendel, a Memorial Sloan-Kettering cancer biologist. “That is exciting, and it also means we have a lot to learn about it.”

I will likely be years before any patients can be treated with this new drug, but its discovery is certainly something to celebrate.

April 27, 2013 — A Pretty Good Pipeline

With all the ecological concern these days, pipelines don’t have an especially good name. Surely they’re a mixed blessing. They deliver all sort of things we can use, but they can pose terrible risks to the environment.

Here’s one pipeline whose value everyone can agree on. It’s the pharmaceutical research pipeline. I saw an article today directing me to an online brochure detailing just how many new medicines are in the pipeline for blood cancers.

From the brochure: “Pharmaceutical research companies are developing 241 medicines for blood cancers — leukemia, lymphoma and myeloma. This report lists medicines in human clinical trials or under review by the U.S. Food and Drug Administration (FDA). The medicines in development include 98 for lymphoma, including Hodgkin and non-Hodgkin lymphoma, which affect nearly 80,000 Americans each year.”

The brochure includes this chart (click to enlarge), which details the complex process each of these drugs must go through before they’re ready for prime time:

Most don’t make it: not even to clinical trials. Out of many thousands of promising compounds, only about 250 get real scrutiny as possible clinical-trial material. Of these, only five get tried out on real, live patients.

Four out of these five drugs turn out to be ineffective, or deliver side effects that are just too intolerable. That leaves just one chemical compound out of 5,000 to 10,000 that makes it through clinical trials into production.

This, of course, is why new drugs cost so much. The companies have to set aside enough money to pay for all those failed experiments. Patents allow the companies exclusive manufacturing rights for only a limited number of years. Once that time period has elapsed, the generic manufacturers start selling their own inexpensive knock-offs (and, of course, their research and development cost are negligible). The original manufacturers drop their prices to compete, and begin looking to whatever new formula is next coming down the pipeline.

It’s a complicated system. I wouldn’t want to be the accountant who figures out the financial risk and tells the company executives how much they need to charge. But I am glad to know this process is taking place — and that the outlook for new blood-cancer medications is so promising.

With every new drug that emerges from the pipeline, my prospects for living out a normal lifespan, even with my lymphoma — now quiescent, thank God — look better and better.

April 12, 2013 — In the Gray Area

From time to time, I take advantage of educational conference-call opportunities that are made available by some of the leading cancer research and patient-support organizations. This afternoon, I listened to one that featured Dr. Owen O’Connor of Columbia University and Dr. Bruce Cheson of Georgetown University, both of them lymphoma specialists.

I’ve heard Dr. Cheson numerous times in the past (that's him to the left). Dr. O’Connor was a new name to me (see below for his photo).

The program was sponsored by CancerCare.org.

Often, my chief take-away after listening to such programs is to feel reassured that I’m pretty much on top of the subject of recent advances in lymphoma treatments. That, in itself, is encouraging.

Today, though, I actually heard a few things I hadn’t heard before. Or, if I did hear them before, they didn’t register with me.

The first has to do with the vexed question of what sub-type of NHL I actually have. My initial diagnosis was for small B-cell lymphoma, which is usually understood to be an indolent form of the disease (as is the relatively common follicular lymphoma). My second-opinion from a pathologist at Memorial Sloan-Kettering in New York, however, identified a significant number of large cells (more dangerous, but also more susceptible to curative treatment), which set me out on the chemotherapy journey on which I embarked in early 2006. The new diagnosis at the time was “diffuse mixed large and small B-cell.”

As a result, when I attend lymphoma educational conferences where they ask participants with B-cell NHL to break out into workshop groups, some follicular and others large B-cell, I never quite know where to go.

Today I heard Dr. O’Connor speak of the fact that, when it comes to diagnosis, there is often a significant gray area between high-grade (somewhat more aggressive) follicular lymphoma and diffuse large B-cell. He also said there are well-documented examples of “histologic transformation of follicular lymphoma,” which means that a patient’s disease actually changes fro one form to another.

I’m not saying that happened to me, necessarily. It’s just that it highlights how the pathology reports that doctors often present to patients with such certainty are sometimes as much an art as a science.  Dr. O’Connor pointed out that, in the case of some patients, if you were to present the same pathology report to ten different pathologists, as many as three or four of them may differ from the others with respect to grading of the disease.

That would put me squarely in the gray area, it would seem. It also means I’m likely always to have difficulty deciding which workshop group to join.

Generally, the news continues to be encouraging. Both doctors emphasized that, in the world of B-cell lymphoma, there are a great many treatments to choose from in the event of relapse. Here’s hoping I’ll never need them, but in case I do someday, it’s good to know there’s a choice.

They also made me feel like the R-CHOP treatment — harsh as it was — was, indeed, the most appropriate choice for me at the time. One of the callers in the question-and-answer session was wondering whether it’s best for a newly-diagnosed follicular lymphoma patient to start off with Rituxan only, rather than more traditional chemo agents. Dr. Cheson was quite clear that, the younger the patient is, the more important it is — all things being equal — to start with the harsher treatment first. Not only are the benefits likely to be longer-lasting with traditional chemo, but older patients are more likely to have difficulty tolerating it. So, it’s better to use it while you can, as a primary rather than a refractory treatment, while you’re relatively young.

I’ve often wondered, as well — especially as I speak to other patients whose disease is quiescent and who are pursuing long-term maintenance Rituxan treatments — whether watchful waiting continues to be the best course of action. Dr. Cheson put my mind at ease in that regard, by repeating news of some research studies I’ve already heard about. Specifically, these studies have found that, while maintenance Rituxan treatments may cause longer remissions, when everything is said and done, the overall survival rates of those who have had these monthly IV drips is no better than those who have not.

Anyway, it was a productive and reassuring hour to spend — even considering the ambiguity that goes along with living in the gray area. Thanks to the good folks at CancerCare for putting on such a useful program!

October 21, 2012 – Death of a Cancer Treatment Pioneer

Today, I run across an obituary for a true cancer treatment pioneer, Dr. E. Donnall Thomas, who died at age 92.

I’d never heard of Dr. Thomas till I read his obituary, but I’ve certainly heard of the procedure he perfected: the bone-marrow transplant.  He shared the 1990 Nobel Prize in Medicine for this work.

His obituary in today’s New York Times includes this:

“When Dr. Thomas began his research in the late 1950s, bone marrow transplants were seen as a frightening last resort. Patients suffered dangerous complications from the procedure, and survival rates were grim. The patient’s immune system would either destroy the transplanted marrow as foreign, or the transplanted marrow, which contains immune system cells, would destroy the patient's lungs, kidneys and other organs.

The only successes were in identical twins because their tissue types matched.

Many physicians abandoned the approach, believing that bone marrow transplantation would never be safe enough to be practical. Dr. Thomas persevered, despite numerous failures and the criticism that he was exposing his patients to undue risks....”

Dr. Thomas’ story reminds us of how difficult cutting-edge cancer research can be.  Sometimes – as was his experience – repeated setbacks lead some researchers to give up on a specific strategy. In such an event, only the truly committed remain in the game.

It takes a certain mix of confidence, stubbornness, and gutsy perseverance to continue to tweak the experimental treatment protocols until obstacles are finally overcome and success is achieved.

Before gladiatorial contests in the ancient Roman coliseum, the equivalent of playing the national anthem was for the combatants to stand before the Emperor and say “We who are about to die salute you.”

There are a great many cancer survivors who could very well bid farewell to Dr. Thomas with a slight variation on that theme: “We who are not about to die salute you.”

A big thank-you to all who persist in the field of cancer research, despite setbacks!

June 25, 2012 – Tweaking the Cocktail

If ever there were a good time to be a lymphoma patient (not that I think there ever is), it’s now.  Every annual meeting of ASCO (the American Society of Clinical Oncologists) seems to offer news of some new variation on treatment protocols that promises a heightened survival rate.

The latest one for follicular lymphoma – as I learn today from an e-mail bulletin sent around by the Leukemia and Lymphoma Society – is a new combination of Rituxan (the monoclonal antibody drug I received along with my CHOP chemotherapy) and an old drug that’s been around for a while, Revlimid:

“John Leonard, M.D., of Weill Medical College of Cornell University presented promising results for a Phase III trial of a new Rituxan combination to treat patients with follicular lymphoma (FL). Dr. Leonard reported that using Revlimid plus Rituxan very much increased overall response rates for relapsed FL patients (73% in this trial vs. 50% for Rituxan only in previous trials). A Phase II trial of this combination for newly diagnosed FL patients is already underway.”

Revlimid, its manufacturers admit on their website, is an “analogue” of Thalidomide – one of the scariest names out there in the field of pharmacology. OK, let’s be real: Revlimid is Thalidomide, but with the drug’s notorious history I can understand why they’d rename it.  I still remember, as a kid, paging through an issue of LIFE magazine with its chilling, black-and-white photos of the children born with horrible birth defects as a result of that drug.  From 1957 to 1961, Thalidomide was commonly given to expectant mothers to prevent morning sickness.  No one knew that many of the children born to these unfortunate mothers would have no arms – other than small, vestigial appendages that could in no way substitute for the real thing. Very sad.  (Not to mention, a gold mine for the trial lawyers.)

As a cancer drug, Revlimid is evidently effective: and, as long as the patient isn’t an expectant mother, it’s supposed to be safe (or, at least, as safe as most other cancer drugs, all of which have a certain risk to them).  Lots of chemo drugs come with a warning label saying they’re not for expectant mothers, or may cause sterility.  Doctors have raised that sort of warning with me, at various times as I prepared for treatment, but when I tell them Claire and I are not only done having children, but that I’ve had a vasectomy, it lays those concerns to rest pretty quickly.

It’s not cheap, though: Wikipedia.com reports that Revlimid (medical name, Lenalidomide) costs an average of $163,381 per year.  Ouch.

Dr. Leonard’s work is only a Phase I trial, with Phase II now underway, so this drug cocktail is a long way from being ready for prime time.  I’m glad to know someone’s out there, though, with the medical-research equivalent of a cocktail shaker, trying out new drug combinations.  From early indications, chances are that this one may be in production in several years’ time, so it's one more reason to be hopeful, should the day come when I need treatment again.

June 12, 2012 – Huh?

Every once in a while you run across a news story, and the only possible reaction to it is.... “Huh?”

That’s how I responded when I read a news article just out, that claims there’s conclusive evidence that overweight men have a better chance of surviving diffuse large B-cell lymphoma than those of more normal weight.

Like I said: Huh?

That news runs counter to every bit of medical advice I’ve been hearing for most of my life.

The article is of particular interest to me because (1) I’m a man, (2) I’m considerably overweight, and was so at the time of my lymphoma diagnosis, and (3) I have something very similar to diffuse large B-cell lymphoma.

OK, my grading was actually “B-cell, diffuse mixed large and small cell.”  That means I had some less-dangerous small cells – the kind present in indolent, “follicular” lymphoma – mixed in with the large ones.  It was the presence of the aggressive larger cells, as discovered by the second-opinion pathologists at Memorial Sloan-Kettering as they reviewed my biopsy slides, that put me on the chemotherapy bandwagon straightaway (do not pass GO, do not collect $200).  Otherwise, watchful waiting would have been a viable option.

The only time in my life when I’ve been of statistically normal weight was a period of time in my very late teens and early-to-mid-20s.  Both before and after that time, I’ve struggled constantly with my weight.  My failure to turn around my tendency towards obesity has been one of the greatest sources of guilt and shame in my life.

Ever since cancer has come onto the scene, it’s been even worse.  It’s hard to marshal the emotional energy to change my eating patterns when I’ve been through the sort of struggle I have.  There’s a part of me that says to the rest of me: “Why should you suffer through a diet when you’ve already suffered through so much else?  Live a little!”

Then this article comes along, suggesting that the spare tire I’ve been carrying could very possibly have been my life-preserver.  Go figure.

The article’s appropriately cautious about the study’s results.  The researchers don’t want anyone to go out and start lobbying for hot-fudge sundaes to be included in the treatment protocols.  Quite sensibly, it makes the point that obesity is a proven risk factor for all manner of very bad things that could happen to a person, medically, and that there’s every reason to lose those extra pounds.

But still, it makes you think.

And this one I’ll be thinking about for a very long time.

October 6, 2011 – Designer Drug Is a Little Closer

Back in October, 2007 and again in June, 2009, I reported on the research success of an idiopathic vaccine treatment for indolent NHL called BiovaxID.  I’ve been following the progress of this research with particular interest ever since, because I was briefly considered for a clinical trial of it when I was first diagnosed.  While that clinical trial proved not to be an option for me (after I was diagnosed with an aggressive from of NHL, besides the indolent form the researchers were targeting), it’s one of the newer treatments that continues to hold promise.  By the time my indolent NHL-dragon awakes from slumber and again rears its ugly head, BiovaxID will likely be one of the arrows in the quiver.


A current financial news article reports that BiovaxID is just about ready for prime time.  Biovest, the company that holds the patent, has just formally petitioned the FDA for regulatory approval.

The wheels of government bureaucracy grind exceeding slow, but this is progress, all the same.

It’s a little odd to read about it in an internet investors’ newsletter called Market Watch.  Articles like this one are meant to help aspiring venture capitalists see what's coming from afar, so they can decide whether  shares of Biovest’s stock are an attractive place to park some of their simoleons.

In the world of Big Pharma, though, that’s the way it works.  It’s not just altruism that keeps those researchers peering into their microscopes and hovering their eyedroppers over petri dishes.  If you can “build a better mousetrap” by curing or pushing back some dread disease, the investment world will beat the proverbial path to your door.  That means some big, fat paychecks for the people in the lab coats, and even fatter ones for those risk-taking financiers who advanced them the money to do what they do best.

BiovaxID is the ultimate designer drug, in that it’s custom-manufactured for each patient.  Starting with some biopsied tissue, the drug company goes back to the lab and cultures a special version of the drug that will be most effective for that person’s body chemistry.

This feature of the treatment stretches the meaning of the word “drug.”  You’ll never be able to amble down to your local pharmacy and pick up a childproof bottle of the stuff.  Each person’s formula is one-of-a-kind.

What BiovaxID will eventually cost, I have no idea. It sure won’t be cheap. It is to ordinary drugs as a Saville Row bespoke tailor is to K-Mart.

Whatever it takes to get the researchers as far down the road as they’ve gone on this one, I’m glad they have.

Another reason for hope!

October 1, 2011 – Drug Shortages: I’m Not Alone

According to a recent item in The Atlantic, I’m not alone in experiencing the effects of a drug shortage (the Thyrogen shortage, that’s currently shoved my radioactive-iodine treatment onto a siding).

The FDA has documented no fewer than 178 drug shortages so far this year. From the article: “The number of drug shortages has been steadily rising every year since 2006, when 56 shortages were reported. It increased to 90 in 2007, 110 in 2008, 157 in 2009, and finally to 178 in 2010, more than tripling in four years.”

There are lots of reasons for these shortages, evidently, including: “manufacturing problems, drug purity issues, and discontinuations of some older, less profitable drugs by drug companies.”

The FDA’s trying to get Big Pharma to agree to a regulation that would require them to give 6 months’ notice before discontinuing a drug, to allow the FDA time to seek new avenues of supply for patients who need it. The pharmaceutical companies are resisting this, complaining that it’s often because of oppressive FDA regulations that they can’t make a profit on their drugs in the first place.

What insufferable arrogance! Who’s the regulator here, and who’s the regulated?

Still no word from Memorial Sloan-Kettering on when they may get some Thyrogen and be able to schedule my treatment. Late August has become late September, and still no word. Now we’re into October.

Considering the extremely lucrative nature of the drug-manufacturing business, and the critical importance of some of these medications for patient health, you’d think these companies could take the small steps necessary to at least let patients know a shortage is coming.

But that would be too ethical, it seems.

August 11, 2011 - A “Really Huge” Cancer Research Breakthrough

Anyone with a personal interest in cancer treatment will want to read this Los Angeles Times article, about a very significant research breakthrough by scientists at the University of Pennsylvania.

It seems they’ve found a way to modify a patient’s own T-cells, so that, when injected back into the patient’s bloodstream, they destroy a variety of different types of cancer cells. Each re-engineered T-cell packs a wallop: it can kill over 1,000 cancer cells. In the patients who were treated with this experimental regimen, the T-cells had a life of over 3 months, and the cancer has not recurred a year later.

This is as close as scientists can reasonably expect to get to a “natural” cancer treatment. It’s a way to, essentially, educate a patient’s own immune system to do what it should have been doing with those cancer cells in the first place.

“This is a huge accomplishment - huge,” says the Dean of Harvard Medical School. Considering that Harvard is essentially a competitor of Penn in seeking this sort of research breakthrough, this is high praise.

This is the sort of news that gives hope to those of us living with cancer. This is just early research, of course, and “not ready for prime time” as an off-the-shelf treatment option, but it holds great promise for the future.

Way to go, University of Pennsylvania researchers!

April 21, 2011 – Radiation Pill?

It seems lymphoma treatment isn’t the only cancer-treatment field that’s rapidly changing. Today I come across an article on my other cancer – thyroid cancer – indicating that one treatment that’s been talked about for me is currently being reconsidered by the experts.

I’ve been hearing all along that, once my thyroid is removed surgically, I’ll probably need to follow up with a single radioactive-iodine treatment. This is a dollop of radioactive material encased in a small pill, that I would swallow several weeks after surgery. Because thyroid tissue thirstily slurps up iodine, if it should happen that there’s any thyroid tissue remaining in my body after the surgery, the radioactive iodine would zap it.

Now, it turns out the radioactive iodine is risky in itself, and is possibly the cause of some secondary cancers. Recent studies indicate that a more nuanced treatment decision now needs to be made, weighing the likelihood that there is indeed any remaining malignant thyroid tissue against the slight – but real – risk of the radioactive iodine running amok and causing another cancer elsewhere.

The American Thyroid Association is now saying that radioactive iodine “should be used selectively and [only] in patients with intermediate and high-risk thyroid tumors.”

So, with a nodule presently at 1.5 centimeters, how’s my tumor classified? I didn’t ask Dr. Boyle about precise staging, so I can’t be sure.

That’s one thing I’ll need to remember to ask the doctor about, as the time of surgery draws near.

In the meantime, it’s Holy Week, and I’ve got a whole lot of other things on my mind. Sermons to write!

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.