September 29, 2010 - Watch Those Cancer Cells Get Zapped

Thanks to Betsy de Parry for posting a link on Facebook to an animated slide show about how targeted therapies (like Rituxan, the drug I received) first locate, then take out, cancer cells.

It's on the website of the National Cancer Institute. The presentation is in a lot of different segments. You need to click on the links in the menu to the right to move on to the next one.

It's nice to see those cancer cells getting zapped, even if it's only an animation!

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.

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.

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...

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 10, 2008 - Loss of Control

A friend of ours, Mary Beth, sent me a link to a doctor’s blog, “Musings of a Distractible Mind,” by Dr. Rob, an internal medicine doctor from the Southeastern U.S. It’s an insightful and witty blog – well worth a visit.

I was interested in a post, “Dangerous Information,” from June 25th. In it, Dr. Rob engages in a good-natured rant about patients who habitually question the prescriptions he writes:

“A patient left me a message earlier this week: ‘I was reading the information on the drug that Dr. Rob prescribed, and I am really worried about it.’ He went on to say he was faxing me the prescribing information, just in case I didn’t realize the risk of the medication.

I hate it when people do this. Do they realize that I studied for eight years and have practiced another thirteen? Why would I prescribe something for them that I don’t know about? Why would I put my name behind a ‘dangerous’ prescription? Why would they bother coming to me if they thought I did not know these things?

I don’t really take it as a personal insult, and I do feel that it is fine to question the doctor. I am sure it has happened that I have given prescriptions with interactions and/or side effects that I did not think of, but there are some levels of questioning that cross the line. I am an internal medicine doctor, so medications are my tool. Would you ask a surgeon, ‘Are you sure you should make a midline incision? Do you think that a lateral approach may be better?’ Do you tell a cardiologist, ‘I read on the Internet that the non drug-eluting stents are better than the drug-eluting ones’? Do you ask the radiologist, ‘Don’t you think that density could represent pleural plaque rather than an infiltrate?’ Probably not.”

I posted this comment in Dr. Rob’s blog:

I’m not sure most patients who question doctors’ prescriptions do so because they don’t trust the doctors. I think they do it for the same reason so many people are obsessed finding that miracle food (or avoiding that dangerous food) they imagine will prevent cancer. It has to do with loss of control.

Unlike submitting to a surgeon’s decision on where to place the scalpel, popping a pill into our mouths is something we do have some small measure of control over. And so, some of us hang onto that tiny shred of control, even if it makes our doctors suspect, sometimes, we have no confidence in them.

A great many illnesses happen regardless of how we choose to live our lives: and that truth is a hard one to absorb. We like to imagine the world is a fundamentally safe place for people who work hard and try to do the right thing, when in fact it’s not. Bad things do happen to good people. Most of us would rather cling to the illusion that we are masters of our own destinies.

I've got non-Hodgkin lymphoma, a disease for which there are few known environmental or inherited causes. Some unlucky people just get NHL, and medical science doesn’t know why. A cancer like mesothelioma isn't like that. Most cases of that disease, I've read, result from asbestos exposure. Luck has nothing to do with it (unless you count the decision to take a job in an insulation factory in the 1960s a matter of bad luck). The same goes for people with leukemia who were living downwind from Chernobyl when that nuclear power plant melted down. A person with asbestos-related or radiation-related cancer knows exactly where it came from. And there’s some small - admittedly, VERY small - comfort in that.

So, next time one of your patients brings in some article from a wacky natural-health magazine about the benefits of some cactus extract, or starts questioning whether the prescription you’ve prescribed safely for hundreds of patients could make them sicker, consider this: it may be because your patient is struggling to absorb the harsh truth that some sickness just happens.

Cancer is a scary thing. That’s why the field of cancer treatment is a congenial playground for all manner of charlatans and quacks – and why so many cancer patients are so easily bamboozled by them. Yes, it’s a very good thing for us to educate ourselves, becoming as well-informed as we possibly can. Yet, let us also remember, as we scan the Internet, that doctors who have studied long and hard to learn about our condition are our best, most trustworthy advisors.

Thanks, Mary Beth, for the link to this excellent blog. And thanks, Dr. Rob, for getting me thinking about this.

March 19, 2008 - Zevalin Knocks 'em Down

Here’s an encouraging development from the world of lymphoma research, reported in the British medical journal, The Lancet.

A recent study in Italy has returned very encouraging results for the radioimmunotherapy drug, Zevalin, in treating advanced follicular lymphoma patients. This was a first-line treatment: none of the patients had ever been treated before. Each of these 61 patients first received 6 treatments with a chemo cocktail of fludarabine and mitoxantrone (that’s different from the R-CHOP combination I received), then two infusions of Zevalin.

According to a Reuters news report, after chemo alone, the results were pretty impressive: “The overall response rate after chemotherapy was 98%: 43 had a complete response, 17 had a partial response, and 1 had progressive disease.” But then, when Zevalin was added, the results were even better:

“All but two patients had a complete response after [Zevalin] treatment.

Furthermore, 14 of 18 patients tested achieved molecular complete remission, defined as the absence of BCL-IgH rearrangement in bone marrow and peripheral blood.

‘With a median follow-up of 30 months,’ Dr. Zinzani's team reports, ‘3-year progression-free survival was estimated to be 76% and 3-year overall survival 100%.’”

This is concrete evidence of the truth of the “treatable” adjective, that’s part of the “incurable-but-treatable” label frequently used to describe follicular NHL. The effectiveness of radioimmunotherapy drugs in the treatment of the type of lymphoma I have seems indisputable.

Zevalin, of course, was one of the radioimmunotherapy drugs nearly pulled from the U.S. market at the end of last year, because Medicare reimbursement rates had been set too low to pay for their continued manufacture (the other one was Bexxar). Thankfully, Congress bailed these two drugs out at the eleventh hour.

It’s encouraging to know that, at such time as I will require further treatment in the future, the doctors will have effective medicines like these to pull out of their toolboxes.

February 13, 2008 - Hope Does Not Disappoint

“What price do you put on hope? Is $3,000 a week too much?” So begins a health column from the February 4th Newsweek. Jerry Adler, the columnist, is telling the story of a couple named Said and Mary Nedlouf. She had advanced breast cancer that her oncologist was calling untreatable. Her husband didn’t want her to lose hope. So, they agreed she would go to another doctor and pursue costly homeopathic treatments that weren’t covered by their insurance. The bottom line? $41,000, which the Nedloufs paid out of pocket.

The treatments did Mary little good. She died anyway, pretty much when the traditional-medicine doctors had predicted she would. As for Said, when he recalls the homeopathic doctor’s questionable advice, he’s left feeling angry. He feels the homeopath gave his wife false hope, encouraging her to hold out for a cure – when she would probably have been better advised to “get her affairs in order,” as they say.

This doctor, says the grieving husband, “robbed me of precious time to console her, to come to closure, to prepare for her departure.”

I place pretty near zero confidence in homeopathic treatments, myself. Everything I’ve read about this school of alternative medicine – a pharmacology based on an odd, 19th-century premise that repeatedly diluting medicinal substances with water makes them more (rather than less) effective – sounds like complete hokum to me. Even if homeopathic medicines did have some real medical value at full strength (a premise that’s very much open to question), then by what stretch of the imagination does diluting them make them more effective?

Yes, I know some people claim to have derived benefits from homeopathic treatment – and I would never presume to tell fellow patients not to seek out an otherwise-harmless treatment they think could possibly help. I'm sure, also, that many homeopathic practitioners are fine people, and practice listening skills in ways not so many traditional physicians are willing or able to do. Yet, I also know the placebo effect is a powerful thing. I see little evidence that homeopathy is more effective than a sugar pill, if that sugar pill is prescribed by a doctor the patient trusts.

The Newsweek article raises, for me, the question of hope. What is it? Where do we find it? How do we maintain it, over time? When – if ever – should we stop hoping?

“Hope,” says Paul in Romans 5:5, “does not disappoint us, because God’s love has been poured into our hearts through the Holy Spirit that has been given to us.” This is an image of abundance, abundance in the midst of utter desolation.

Paul can speak of such things because he has already seen, in his own life, the love of God poured out in such abundance that it overflows. Paul doesn’t speak of suffering as one who has never known it. Rather, he speaks as one with scars on his soul – one who has known not only persecutions but also what it feels like to have been a persecutor himself, and to have repented of that evil.

“I know what it is,” he writes soberly to the Philippians, “to have little, and I know what it is to have plenty. In any and all circumstances I have learned the secret of being well-fed and of going hungry, of having plenty and of being in need.” (Philippians 4:12).

Then, and only then, does Paul goes on to add these well-loved words: “I can do all things through him who strengthens me” (v. 13). Paul can make that audacious claim because he has had the experience of casting his body off a spiritual cliff, and finding God’s arms were there to catch him.

In what, indeed, does our hope consist, as cancer patients? Is it in the unique pharmacology of the next new treatment to come down the pike? Or, is hope something else altogether, something we discover deep within us and bring to our work of self-healing?

There’s also a communal aspect to hope. In the words of Chinese author Lin Yutang, “Hope is like a road in the country. There was never a road, but when many people walk on it, the road comes into existence.”

I find something deeply profound, and remarkably true-to-life, about that humble image. Yes, of course it is the imprints of many feet that make a rustic footpath. It’s easy to see the footpath when others have been that way before. Yet, who is it who first grasps the vision that there ought be a pathway here, and begins the work of walking it?

Poet Emily Dickinson calls hope:

“...the thing with feathers
That perches in the soul,
And sings the tune without the words,
And never stops at all...

I’ve heard it in the chillest land,
And on the strangest sea;
Yet, never, in extremity,
It asked a crumb of me.”

No: hope does not disappoint us – we, who live with cancer. True hope, hope that’s founded on something stronger than mere pharmaceutical formulas, can never disappoint.

Another Way for NHL Patients To Fight for RIT Drugs

I'm posting this e-mail message here as a public service to other patients with forms of NHL that are potentially treatable with the radioimmunotherapy (RIT) drugs Bexxar and Zevalin. Betsy de Parry, a lymphoma survivor and activist, is inviting comments on her blog, which lobbyists in Washington can use to tell Congress about real cases like ours. If you have NHL and are concerned about the possible disappearance of RIT drugs like these, please visit Betsy's blog and post a brief comment there, including basic details of your situation.

(Scroll down to my November 14th entry for more on this issue. I'm including another link to the Newsweek article by Jonathan Alter, that explains this complex issue. CLICK HERE for that article.)

Thanks!

***

Hi All,

As you all know by now, Bexxar and Zevalin are seriously threated. I've been talking, almost daily, with lobbyists in Washington who are working to have the ruling overturned, and they are telling me that hearing from patients is helping them to convince the staffers. They suggested posting a blog and asking people to make comments which they could then print and take to their meetings.

Thus - if any of you want to voice your opinion - short and sweet is fine - you can do so on my blog which is at www.lymphomablog.blogspot.com

We have very little time to accomplish this mission - if the ruling is not overturned by 12/31, it takes effect on January 1. So, language has to be written into a bill which then has to pass before 12/31. Let's hope that push/pull/shove politics doesn't stand in our way.

Thanks so much,

Betsy

P.S. Ok, this is a long shot, but several people, including senator's offices, have said that good old-fashioned protests work because the press usually picks up the story - and what could be more heartbreaking than cancer patients pleading for drugs to save their lives? Karl Schwartz is organizing one for next Thursday in front of Senator Specter's office in Pennsylvania. Does anybody want to think about going to Lansing and protesting in front of Stabenow's office? I'll do it if at least 9 or 10 others want to join. Or in any of your own states?

August 7, 2007 - The Whites of Their Eyes

“Don’t fire until you see the whites of their eyes.” The saying is traditionally attributed to American General William Prescott, at the Battle of Bunker Hill in 1775.

Much as I resist military metaphors when it comes to cancer treatment, that phrase seems apt to me today, after this morning’s second-opinion consultation with Dr. Carol Portlock at Memorial Sloan-Kettering Cancer Center in New York City.

Dr. Portlock says the Memorial Sloan-Kettering pathologist who examined my biopsy slides confirmed that what I’m dealing with is indolent lymphoma – small cells, with the CD-10 protein marker on their outer surface (there’s no sign of the large, CD-20 cells I had previously). My swollen lymph nodes are few in number, and they’re quite small. For that reason, Dr. Portlock is going to recommend to Dr. Lerner a strategy of watchful waiting.

What I’ve experienced, she tells me, is something called “retrograde transformation.” While the larger, aggressive cells were indeed there previously – primarily in the large mass in my abdomen – they seem to have disappeared after treatment, leaving me with indolent (follicular) lymphoma.

There’s a part of me that distrusts the watchful waiting strategy – that wants to just get on with it, and push back against the cancer, hard and fast. Yet, just as there was a certain strategic wisdom in the Continental Army marksmen holding their musket fire until they couldn't miss, so there’s wisdom in waiting to recommence treatment of my lymphoma. Not every cancer treatment is repeatable. It’s best to save the ones we have for when they’re truly needed.

With lymphoma, the doctors have a certain number of arrows in their quiver – more than with many cancers – but, that number is still limited. We can’t just fire them off wildly. We’ve got to make them count.

“Is there any downside to watchful waiting?” I ask.

“Well, sometimes the patient disappears,” Dr. Portlock admits. When I ask what she means by that, she explains that some watchful-waiting patients get overconfident, and – in the absence of obvious symptoms – stop going to the doctor. Then, the silently-advancing recurrence sneaks up on them. By the time they do get back to the doctor, it’s advanced far enough to be truly dangerous. The “watchful” adjective is a crucial part of the formula, in other words. Vigilance is the key.

“You won’t have that problem with me,” I assure her. I have every intention of continuing to go back for scans, at whatever intervals Dr. Lerner recommends.

I ask her how long I can reasonably expect it to take, before my cancer has advanced far enough to require treatment.

Maybe a year or two, she replies. Maybe longer. Dr. Portlock makes a circle with her thumb and forefinger, that looks to me to be about the size of a small grape. This is about how big the malignant lymph nodes should be before we start treatment, she says. We should keep monitoring them using CT scans, at whatever interval Dr. Lerner recommends. (CT scans, she explains, are better than PET scans in this instance. We already know what the enlarged lymph nodes are. We’ve just got to keep measuring how big they are. CT scans are better suited to this purpose.)

When the lymph nodes do get large enough to treat, I ask, what treatment is most likely? Dr. Portlock says treatment with Rituxan only (not chemo, this time) is a possibility. This drug is often effective against follicular lymphoma, and has few side effects.

She also talks about an allogeneic stem cell transplant (that’s the variety in which the stem cells are donated by another person, ideally a sibling). Such a treatment is “potentially curative,” she says, but with the swollen lymph nodes still so small, it’s too early to move in that direction.

I leave feeling upbeat. This does seem to be pretty good news (although, as I’ve said, there’s an impatient part of me that just wants to get on with it).

After a quick lunch in the hospital cafeteria, and after calling Claire to fill her in on the news, I decide to take advantage of having a free afternoon in Manhattan. I walk the five or six blocks over to the nearby Frick Collection, and spend a couple of hours looking at Old Masters paintings. I’ve never been to that museum before, and am impressed by it: it’s smaller and more manageable than the Metropolitan Museum, and contains a collection of very famous artworks indeed: displayed in the home of the collector himself, much as he would have wanted them to be viewed.

A subway ride and a train ride later, it’s back home again.

July 20, 2007 - Relapse

This afternoon, as Claire and I sit in one of Dr. William Lerner's examining rooms, he hands me a prescription for another PET/CT scan. At the bottom, he's written: "DX: Lymphoma in relapse for restaging."

Yes, that's right. I've relapsed.

There's some good news, in the midst of the bad. The pathologist's analysis of my core-needle biopsy sample has revealed only small lymphoma cells. The lab-coated geniuses peering through microscopes found no trace of the larger, aggressive cells that were present at the time of my initial diagnosis.

Dr. Lerner says this doesn't surprise him. Other patients he's had in the past, with the same "diffuse mixed large and small cell" grading, have been treated successfully for the aggressive component of their disease. The indolent, small cells, on the other hand, are always much harder to defeat – in fact, indolent lymphoma is considered "incurable, but treatable."

I ask Dr. Lerner if patients like me, with the "diffuse mixed large and small cell" diagnosis, can in fact be considered to have two different types of lymphoma. He agrees that, yes, that's an accurate way to describe it. So far, the R-CHOP chemotherapy regimen seems to have wiped out my large, aggressive lymphoma cells (please emphasize the "so far," because it will still be some time before we can venture to use the word "cure," referring to those aggressive cells). As for the small, indolent cells, they're likely to keep bugging me for some time to come.

Dr. Lerner conducts a physical examination, spending a great deal of time touching and probing my neck and armpits with his fingers (these are parts of the body where lymph nodes are close to the surface). I ask him if he can feel the same swollen nodes under my jaw and at the base of the neck he felt the last time I was in his office. He says he can't – but, this comes as no great surprise to him. Cancerous lymph nodes swell up, but sometimes they also inexplicably diminish in size.

Locating the tiny scar from the biopsy needle at the base of my neck, he probes that area. He says he can't feel the deep-down, swollen node from which the biopsy sample was taken (but then again, neither could the surgeon, Dr. Gornish, as I lay on the operating table several weeks ago).

So, what's ahead? The first order of business is another PET/CT scan. I'm due for one, anyway – more than three months having elapsed since my last one – so there shouldn't be a problem getting the insurance company to fund it. Second, I'll return to his office for another bone marrow biopsy – I'm due for one of those, too. Third, I'll take those scan results, along with the biopsy slides and pathologist's report, up to Dr. Carol Portlock at Memorial Sloan-Kettering Cancer Center in New York. (She's the lymphoma specialist I've been conferring with, for second opinions.)

As for treatment, Dr. Lerner says there are a number of different directions we could go – and, since this is a slow-moving cancer, we can take our time to consult with other specialists and make up our minds. With this kind of cancer, he admits, treatment decisions "are not black and white." Put a hundred lymphoma specialists in a room, he predicts, ask them what they would do, and they'll come up with a range of recommendations. Here are the possibilities:

• (1) Watchful waiting – It's a slow-growing lymphoma, and I have no symptoms right now, so one approach would be to just wait and see what develops (this approach is more commonly used with older patients, rather than younger ones like me, but it could still be appropriate if the next scans continue to reveal only a few problematic lymph nodes, and if I continue to have no symptoms).

• (2) Aggressive chemotherapy – This would be treatment with a second-line chemotherapy regimen, with the usual grisly side effects. It would almost certainly wipe out all discernible traces of lymphoma – although it's debatable whether it would be more effective, in the long run, than the other options.

• (3) Stem-cell transplant – This is a form of second-line chemo, but the drugs are so toxic, they would take down my entire immune system. The doctors would harvest stem cells from blood ahead of time, freeze them, and use them to rebuild my immune system after the treatments are finished. The stem cells would come either from one of my brothers (allogeneic transplant) , or from my own blood (autologous transplant) . Stem cells from a sibling donor are more likely to wipe out the cancer, because there's zero chance any free-floating cancer cells could slip through the sieve – although they offer their own set of challenges.

• (4) Treatment with Rituxan alone – My R-CHOP treatment was a combination of Rituxan and the four-drug CHOP chemo cocktail. The next time around, I could be treated with Rituxan infusions alone. The side effects of Rituxan are pretty much limited to some uncomfortable reactions during the infusion itself – there's no hair loss, no nausea, no mouth sores, none of the other miserable side effects people associate with chemo.

I ask Dr. Lerner about the radioimmunotherapy drugs, Bexxar and Zevalin. He says that, yes, one of those would also be an option:

• (5) Bexxar or Zevalin – Both these drugs are Rituxan with an added kick: a tiny fragment of radioactive material that piggybacks on each molecule of the medication. The Rituxan does its thing, targeting the CD-20 protein on the surface of the lymphoma cells and sending out its microscopic smart bombs to attack those cells: but, then, the little radioactive hitchhikers deliver their own payload as well, making it a one-two punch. Dr. Lerner's office is not set up to administer Bexxar or Zevalin, but he sometimes refers patients to Jersey Shore Medical Center, which is licensed to deliver these treatments. Bexxar and Zevalin are new drugs, he cautions, and it's still not clear what their long-term effects are. There's some chance the radioactivity could cause long-term damage to my bone marrow – and, since, at age 50, I'm looking ahead to many years of living with lymphoma, this is something he advises I weigh carefully.

I mention the recent article in the New York Times, about the relative slowness of the oncology world to adopt Bexxar and Zevalin (see my June 23 and July 14 blog entries). Dr. Lerner says he isn't entirely happy with the article – he suspects the Times editorial staff has it in for the medical profession, and particularly for the pharmaceutical companies – but the facts about the drugs presented in the article are essentially accurate. He says he especially resents the implication that doctors are influenced by financial considerations when it comes to choosing the most effective treatment to recommend. (For the record, Dr. Lerner impresses me as a person of principle, who would not be easily swayed by such inducements.)

I also mention that, the first time I conferred with Dr. Portlock at Memorial Sloan-Kettering, she suggested I consider a clinical trial for a new cancer vaccine protocol. This clinical trial was limited to newly-diagnosed indolent lymphoma patients – so, once the MSKCC pathologist found aggressive as well as indolent cells in my tissue sample, that deal was off. Although vaccine treatments are not yet generally available, should Dr. Portlock be aware of another clinical trial for which I'd qualify, that would give me yet another treatment option:

• (6) Vaccine therapy – Cancer "vaccines" are quite different from any other kind of vaccine. They're not so much a means of preventing disease, as a way of treating it. If I were to qualify for vaccine therapy, a sample of my malignant cells would be harvested through another biopsy, and sent off to a laboratory. In the lab, a custom vaccine would be cultured from the malignant cells, which would then be injected back into my body at regular intervals, over a period of time. (The clinical trial I was briefly looking at made use of monthly injections over a two-year period.) The vaccine would essentially teach my own immune system how to fight off the cancer.

I feel particularly fortunate in having five, and possibly six, treatment options from which to choose. I ask Dr. Lerner if he would care to rank them in some sort of numerical order, but he says he's not able to do so. There are so many factors involved in the decision – and, besides, I ought to wait and see what the next set of scans reveals, and also hear what Dr. Portlock recommends.

He's just laying out all the possible options, at this point. This is an indolent lymphoma, so we have time.

I feel even more confidence in Dr. Lerner than I did before. He takes the time to explain things, and he seems naturally inclined to take a collaborative approach – not only with professional colleagues like Dr. Portlock, but also with his patients. He doesn't seem to let his ego get in the way: when there are multiple options to be weighed, he's not afraid to admit the complexity of the situation.

Stopping at the scheduling desk on the way out, I book a bone-marrow biopsy for Wednesday of next week. Later, after my return home, I get a call from one of Dr. Lerner's staff, saying that Atlantic Medical Imaging can squeeze me in for a PET/CT scan on Monday morning. A subsequent call from Atlantic confirms that my insurance company readily approved it, so we're good to go.

And how am I doing, in the midst of all this? I'm doing OK. From the time those swollen lymph nodes showed up on my last PET/CT scan back in March, the signs have been pointing to a relapse – so, it's no surprise. I've had plenty of time to get used to the possibility, and there's a certain comfort in finally emerging out of the fog of uncertainty. The fact that there are no aggressive cells in the tissue sample is good news, indeed – probably the best news I could have expected.

More and more, the phrase "living with cancer" seems to be my mantra. It's time to embark on the next stage of that journey.

July 10, 2007 - Have BiPAP, Will Travel

Today, Claire and I drive over to Ocean Medical Center, for the needle biopsy of my superclavicular lymph node (medical jargon for "above the collarbone"). I've been through this procedure once before, for the January, 2006 needle biopsy of the bulky tumor in my abdomen, that confirmed the lymphoma diagnosis and helped chart my whole course of treatment. Once again, Dr. David Feng will conduct the procedure.

Dr. Feng is an "interventional radiologist." That, as I understand it, is a relatively new medical specialty. Basically, an interventional radiologist is a doctor who sticks something into your body, while gazing at images on a screen that are provided by some form of radiological scanner (like an ultrasound or CT scanner). Sometimes the procedure is done for diagnostic purposes (as with me, today). Other times, its purpose is to deliver some form of treatment (such as placing a stent, or performing the "radio frequency ablation" treatment that zaps lung or liver cancer, through a needle inserted directly into the tumor).

As we drive over there, I try not to think about the fact that I'm voluntarily walking into a place where somebody is waiting to stick a needle into my neck.

Ocean Medical Center's Interventional Radiology Suite opened a couple of years ago, to great fanfare. It's a specialized operating room, that contains not only an operating table, but also an array of radiological scanning equipment.

Anesthesia is mostly by sedation, rather than general anesthesia. When the nurse in the same-day surgery staging area asks me about prior difficulties with anesthesia, and I relate my tale of waking up on the operating table twice (during my previous needle biopsy, and during the surgery to implant my port), she explains that I won't be dealing with an anesthesiologist today. Dr. Feng, she says, is his own anesthesiologist – and, I won't see him until I actually go into the operating room.

O.K, I think to myself. I'll go with the flow on this one. Today, I've brought not only my BiPAP mask with me, but the whole BiPAP machine. (It's a lesson learned from experience.) When it comes time for them to roll my gurney down to the surgical suite, the shoulder bag with the BiPAP in it is sitting on top of my legs. I have to be vigilant in hanging onto it. At least one nurse mistakes it for my personal belongings, and tries to whisk it away into a storage locker.

When I get to the operating room, two nurses there introduce themselves, and immediately ask about the black shoulder bag sitting on top of my legs. I explain that it contains my BiPAP machine, that I use it every night for obstructive sleep apnea, and that I'd like to use it during the needle biopsy, if that's O.K. with Dr. Feng. Fortunately, they don't seem fazed by this, at all – although they do grumble a bit that no one from same-day surgery warned them I'd be bringing such a machine with me.

It turns out I'm going to undergo this procedure without even shifting onto the operating table. I'll stay right on the gurney. (Sort of like drive-thru surgery, I think to myself.) There's no convenient place to put the BiPAP machine, so I just shift my legs to one side of the gurney, and the nurse places it on the other side. I put the mask on, myself (I'm a lot more familiar with it than she is), and she hooks up the tubing and plugs the electrical cord into an extension cord she pulls down from the ceiling. I explain that, once the mask is on, I won't be able to talk without first taking it off (the positive airflow of the BiPAP into my nose creates a sort of vacuum effect that keeps my mouth closed: which is precisely why the thing is so effective in preventing apnea – the dropping-down of the soft palate and its side-effect, snoring).

So far, all my dealings have been with the two nurses. I haven't seen Dr. Feng at all, and – with me looking straight up at the ceiling with the BiPAP mask on – I realize the chances of my having any meaningful conversation with him, pre-surgery, are not good.

The nurses shave the area at the base of my neck (I've got body hair there), then apply antiseptic solution. They explain that I'll first get some novocaine injections around the target area, and that I'll feel some pain and burning from that. I do, but it's not severe. Around now, I become aware that Dr. Feng is in the room. Because of my flat-on-my-back perspective (and because the nurses have directed me to turn my head to the left, away from the right side where they'll be working), I never do see him. I hear his voice, though – as he squeezes some ultrasound goo on the base of my neck, explaining that he's first going to take a look at the enlarged lymph node.

The next thing I hear is the nurse, explaining that she's going to start the sedation. Patients generally respond one of three ways, she tells me: they sleep, they get "very mellow," or they get very chatty. She doesn't think I'm the sort that would fit into the third category, she says. (Brilliant deduction, Sherlock; I couldn't say anything with the BiPAP mask on, even if I wanted to.)

As it turns out, my response is somewhere between sleeping and "very mellow." I feel no pain throughout the procedure, although I am aware of a repeated clicking sound – which, I realize, at the time, is probably Dr. Feng, doing whatever snipping-out of tissue he does, using the hollow biopsy needle. It seems like no time at all before I hear Dr. Feng's voice saying, "We're all done." One of the nurses explains that a pathologist has been on hand, and has confirmed that the biopsy produced a large-enough sample for analysis.

I have no recollection of the trip back to the same-day surgery staging area – other than deciding to use the BiPAP there for a while as well, to take a little snooze. I awake a while later, with Claire sitting by my side, and it's not long before the someone feeds me some lunch, and the nurse tells me I can get dressed and head home.

I see Dr. Lerner on Friday, and should learn of the results then.

June 23, 2007 - A Smart Bomb That Could Be In My Future

Searching the Net today, I come across an Associated Press article from about two months ago, about two lymphoma drugs I've heard of, but don't know too much about: Zevalin and Bexxar. These are radioimmunotherapy drugs: a hybrid of radioactive material and genetically-engineered medicine. The gist of the article is that, while these treatments are highly effective against lymphoma, for some inscrutable reason they haven't caught on in a big way. Oncologists have been slow to recommend them to patients. The manufacturers of Zevalin, the article goes on to say, are so disappointed with the sluggish sales that they're seeking another pharmaceutical company to buy the patent from them.

Zevalin and Bexxar work much like Rituxan, in that they target a certain protein, called "CD-20," that's found on the surface of certain types of lymphoma cells (the same type I happen to have, fortunately). The difference is that, instead of chemically neutralizing those cells, Zevalin and Bexxar deliver a tiny particle of radioactive material that accomplishes the same thing. Furthermore, they often bring about longer remissions. The protocol is relatively easy on the patient: just two intravenous infusions, one week apart.

Here's an excerpt from the article:

"The issue: Despite research showing they work well, fewer than 10 percent of lymphoma patients who are candidates for Zevalin and Bexxar ever use them, says Dr. Mark Kaminski of the University of Michigan, a hematologist who co-invented Bexxar.

Why? Specialists cite a complex list of reasons, including that most oncologists aren't licensed to administer the radioactive infusion and must send their patients to a nuclear-medicine doctor. There's also confusion about the risks of radiation, which studies suggest are minimal, and when the drugs work best – early, not as a last-ditch therapy.

‘There's lots of reasons to use them, and there seems to be an inertia against them,' says Dr. Mitchell Smith, lymphoma chief at Fox Chase Cancer Center in Philadelphia. ‘I do see it as unfortunate.'....

‘Basically, [the drug companies] hit a home run' scientifically, says Kaminski. ‘The shock wave that goes through here is that if you can't get this to work in the marketplace, what's the sense of developing anything else along this line?'"

Part of the difficulty, evidently, is the hybrid nature of these drugs. Because they contain radioactive material, the Nuclear Regulatory Commission has to be involved in licensing oncologists to use them. Not many have received that permission, to date. The NRC is used to working with nuclear medicine doctors, not oncologists – yet, this material is delivered through a syringe, not through huge radiology machines in a hospital or clinical setting. And, without a lot of oncologists licensed to give the medications, it's hard for patients to gain access to them.

I remember asking Dr. Carol Portlock, of Memorial Sloan-Kettering, about Bexxar when I was consulting with her at the end of my chemo treatments. She didn't seem too much of a cheerleader for it, at least as a first-line treatment. I remember her saying something about the unknown effects of radiation, years down the road – suggesting that I probably wouldn't want to put radioactive material in my body unless I'd first exhausted all other options. (Of course, I already get radioactive material injected into my veins every time I go for a PET scan.)

For me, this raises questions about the marketing of cancer drugs. A big part of oncologists' profits come from the drugs they sell to patients. Unlike most other medical specialties, oncologists – at least those oncologists who own and operate their own infusion suites – are both physicians and pharmacists to their patients. If there's a drug they're not yet licensed to sell, it's understandably not going to be on their radar screens – at least, not the same way the medications sitting on their shelves are.

Anyway, it will be interesting to see how the thinking about drugs like these may change, in the next few years. If it turns out that my upcoming biopsy indicates a relapse, I wonder if I could be using oncological "smart bombs" like these sooner than I think?