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 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.

September 23, 2007 - Hospital Hospitality

It’s not only in Africa that the poor have difficulty obtaining cancer treatment. The same thing is happening, it seems, in the USA. Under newly revised Federal Medicaid guidelines, the government will no longer reimburse hospitals for chemotherapy provided to illegal immigrants (Sarah Kershaw, “U.S. Rule Limits Emergency Care for Immigrants,” New York Times, September 22, 2007).

Some may find it surprising that our government provides any medical reimbursement at all for illegals. Yet, Medicaid guidelines evidently contain a limited provision that underwrites the cost of emergency treatment for non-citizens. What’s happened is that the Federal government’s regulation-writers have now decided that chemotherapy, by its very nature, is never an emergency. Given the high cost of most forms of chemo, I can understand why government bean-counters would be inclined to make such a declaration. But, I still don't like it.

I’m glad our country covers the cost of emergency-room treatment, at least, for indigent people within our borders. It’s the humane thing to do. The word “hospital” has its roots in “hospitality,” after all. If the government didn’t provide any reimbursement at all, then hospitals would undoubtedly extend some level of care to illegal immigrants anyway, then write the expense off as a loss. Eventually – at least in the case of the most financially-stressed urban hospitals – some of that expense would find its way back to the government, in the form of subsidies that keep hospitals from going bankrupt and closing their doors.

I know a minister who works with Hispanic people in our local area. He’s escorted quite a number of them to the hospital, when they needed treatment, serving as interpreter and general go-between. Those who are here illegally often avoid seeking medical care, sometimes endangering their health and even their lives – even though the local hospitals aren’t particularly interested in reporting people to the INS. (I’m not sure they even can, under HIPAA privacy regulations.)

My colleague told one story about a young man who had broken his arm. He surely couldn’t go without treatment for something like that, nor could he travel back home to Mexico in pain. I presume Medicaid picked up most of the cost, although perhaps he paid some of it himself (he is employed, after all, which is why he’s in this country in the first place). I’m glad Medicaid is there to cover cases like his.

In countries with universal health-care coverage, like Britain and Canada, emergency treatment is often provided to visitors free of charge. I found this to be true when I was in Scotland, some years back (it was just treatment for a fever, but I was surprised they wouldn’t let me pay). Another colleague of mine had to have emergency surgery recently, while on vacation in Canada. I’ve heard he was very impressed with the quick and efficient response of the Canadian health-care system (whether the Canadians will subsequently try to collect from his medical-insurance company, I have no idea).

Yet, what about chemotherapy? As the Times article points out, there’s a considerable gray area here. Some doctors evidently consider certain forms of chemotherapy to be an emergency treatment, or a palliative treatment in the case of pain. There are some cases when, if cancer is left untreated, it will soon become a true emergency, anyway.

Illegal immigrants who come down with cancer are in an unenviable position. Depending on what country they come from, treatment may not be available back home at all. Here in this country, they face fears of deportation (however unfounded) if they show their face in an emergency room, and even then, they’ll likely receive only the bare minimum of treatment. From here on in, that treatment will only include chemotherapy if the hospital is willing to eat the cost, or if the State government is willing to go solo and cover the expense, without Federal subsidy.

All this makes me feel fortunate, indeed, to have medical insurance, and – as a citizen – to have the minimal Medicaid safety net underneath me, should I ever lose my coverage and become indigent.

How is that I’m so fortunate as to live here, to be gainfully employed, and to receive some of the best cancer treatment available, while sisters and brothers from other lands must go without? That’s a question for another day. Yet, I’m grateful, all the same.

December 23, 2006 - Back in Control?

I read something interesting the other day – some eloquently-crafted reflections by Elissa Rubin, a television producer and friend of Leroy Sievers, the National Public Radio commentator who’s also keeping a blog about his experiences with cancer. Elissa composed this reflection after visiting a chemo-infusion facility at Johns Hopkins Hospital in Baltimore, while filming a special on cancer for the Discovery Channel. Leroy posted it in the December 20th installment of his blog, My Cancer:

“What struck me almost instantly was that no one really looked sick. People were in street clothes, flannel shirts and blue jeans, carrying purses and computers. There was a woman in a purple cashmere sweater, one man in an elegant business suit. No bathrobes, no hospital gowns. Aside from looking a little tired, no one looked like he belonged in a hospital. Or that their lives now hinge upon what happens in this room, or that each one now exists in a world of prognoses and time limits. None of that was evident. I felt like I was looking around the platform of a metro station, except for the surreal fact that everyone was hooked up to a machine, with chemotherapy running through their veins, killing the cells that are trying to kill them.

Then you look around and think about what it means to come here, every week, sometimes from hundreds of miles away, and sit plugged into a machine for six hours. You see a room of horribly interrupted lives – the job promotion that just couldn't be taken, the missed soccer games, term papers that would have to be turned in next semester, maybe next year. Marriages thrown into shock, children put in the upside-down position of having to worry about their parents. If anything, this should be a place of raw emotion on display – after all, everyone is in the same position and everyone knows what the person next to him is probably thinking and feeling. It should have been a room filled with anger, yelling, objects crashing against the wall – yet no one even looked particularly sad. This was a place of remarkable calm. Maybe because it was a place – the only place right now – that offered anyone any hope. People were here to fight their cancer, to get better, to keep on living. This was the place for the people who have that option – the so-called lucky ones. At least their doctors were able to offer a plan – one that explicitly said, ‘You do have a chance to beat this, to live longer.’ This was a room of science and medicine, bright lights, protocols and doctors. Finally, there was an opportunity to do something to a disease that had stripped you of all control.”

That experience of being stripped of control goes with the territory, for those who have cancer. So many aspects of life are put on hold, when the single most important thing you can do is to sit next to an IV pole and wait for the drip, drip, drip of those toxic compounds. When it’s all over, and that blessed word “remission” resounds through the corridors of the mind, is there a corresponding return of the feeling of being “in control”?

Only some of the time – at least, that’s been my experience. I seem to alternate between taking up the tasks of life with enthusiasm and waiting for the other shoe to drop. I’m living into this experience of survivorship one day at a time.

Being a survivor isn’t as easy as it may seem, to those who haven’t been through a life-threatening experience. One may imagine – from the outside, looking in – that, once the all-clear is sounded, everything simply reverts to the way it was, pre-cancer. Not so. There’s a new appreciation for what’s important in life – and a corresponding impatience with everything that isn’t. It’s hard to make long-range plans. Like nearsighted people who have lost their glasses, we cancer survivors can only see so far. We live in the present, more than we used to. In the back of our minds is a low-level, but persistent anxiety, that bobs up to the surface of our minds, unbidden: What if it comes back?

In such moments, there’s still that worrisome feeling of loss of control. We no longer see ourselves as captains of our own destiny (as though we ever were).

A ministerial colleague shared this prayer, a couple of years back. I believe she said it’s from a book called Prayers in Celebration of the Turning Year, by Edward Tyler:

Since we cannot make the journey backward into innocence,
help us to go forward into wisdom.
Since we cannot begin again from the beginning,
help us to go faithfully on from here.
Since we cannot turn ourselves by our own willing,
will you turn us, Great God, to yourself.

October 11, 2006 - Chemo Brain?

One of the more controversial side-effects of chemotherapy is something called "chemo brain" – experiences of mild confusion, mental fuzziness or loss of memory that occur both during and after chemotherapy. Many doctors deny that chemo brain exists, as a discrete side-effect – seeing it as simply another aspect of the stress, fatigue and general emotional strain that are part of living with cancer. Many chemotherapy veterans, though, aren't so sure.

I can picture several members of the support group at the Cancer Concern Center discussing the subject, at one of the weekly meetings. "Oh, yes," they were saying, nodding their heads vigorously. "Chemo brain is real."

I also have a memory of asking Dr. Lerner about it, as he was briefing me on what side effects to expect, as I began treatment. His reply was that, yes, he'd heard patients use the term, but he hadn't seen anything yet to suggest there's a physical explanation for it. He sounded skeptical, although he didn't categorically rule it out.

Now, there's a new study that suggests that chemo brain is a real phenomenon, that may continue for as long as ten years after treatment. To quote from a Yahoo! News story of October 5, "Chemo Has Long-Term Impact on Brain Function" (based on a Reuters press release):

"The researchers, from the University of California, Los Angeles, found that women who had undergone chemotherapy five to 10 years earlier had lower metabolism in a key region of the frontal cortex.

Women treated with chemotherapy also showed a spike in blood flow to the frontal cortex and cerebellum while performing memory tests, indicating a rapid jump in activity level, the researchers said in a statement about their study.

‘The same area of the frontal lobe that showed lower resting metabolism displayed a substantial leap in activity when the patients were performing the memory exercise,' said Daniel Silverman, the UCLA associate professor who led the study.

‘In effect, these women's brains were working harder than the control subjects' to recall the same information,' he said in a statement."

The study appears to be of a relatively small group, whom researchers asked to perform simple memory tests while undergoing PET scans. Published in the online edition of Breast Cancer Research and Treatment, it focused on just "21 women who had surgery to remove breast tumors, 16 of whom had received chemotherapy and five who had not." The article doesn't mention whether researchers were focusing on certain chemotherapy medicines only, or whether they were generalizing to consider all chemotherapy.

Still, their findings are suggestive – although I imagine that further studies, with much larger numbers of subjects, will be needed to satisfy all skeptics.

For now, the present state of affairs will probably continue, with many doctors expressing doubts, while a significant number of patients provide anecdotal evidence that – from their point of view, anyway – chemo brain is real.

As for me, I can't say for certain that I've experienced it. Sure, in the days following each chemo treatment, I found it hard to read for any length of time, or to concentrate on complicated tasks. But I could simply attribute that to the fact that I was feeling lousy. I could have said much the same thing about times in the pasts when I've had the flu.

As for any long-term effects of chemotherapy on memory, I can't say I've noticed any of those, either. Sure, I find it hard to recall someone's name, on occasion – and there have been times when I've wondered whether that's a result of chemo brain – but I can't say for sure that's the cause. I'm going to turn 50 in a couple of weeks. You can't expect to get that far in life without the mental machinery casting off a few nuts and bolts.

Those of us dealing with cancer need to pay close attention to confirmed medical findings from research studies, but it also pays to listen to the anecdotal experience of others. That two-pronged approach to information-gathering is, I think, the best way.