End of Summer Blog-Break

Dear Readers,
ML will take a blogging break through Labor Day. I hope the storm doesn’t cause too much damage.

Stay safe, wherever you are, and enjoy these end-of-summer days!

– ES

waves (stock photo)


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Considering Steve Jobs, Medical Diagnoses and Privacy

Yesterday morning I wrote a short post on CelebrityDiagnosis.com. By evening, news broke that Apple founder and CEO Steve Jobs resigned from his position, presumably for reasons of his health.

What’s public, by Jobs’ decision, is that he had a relatively good, typically slow-growing kind of malignancy in the pancreas, a neuroendocrine islet cell tumor. He informed Apple employees by email about his diagnosis in 2004, when he was 49 years old. Since then he’s had a liver transplant. Possible complications of that surgery, or the tumor itself, have led to considerable speculation. But little is known about the details of why he took medical leave in January and is stepping down now.

In a published letter to the Apple Board and Community, he wrote yesterday: “I have always said if there ever came a day when I could no longer meet my duties and expectations as Apple’s C.E.O., I would be the first to let you know. Unfortunately, that day has come.”

The letter was “short and classy,” in David Pogue’s words, and I agree. I respect Jobs’ decision to keep the details of his medical condition private. That’s the thing – and where this is post is heading.

When public figures are open about their illnesses, it can be helpful, instructive and even necessary. For example, if a political figure, say Fidel Castro or Hugo Chavez or Dick Cheney, with considerable power develops a cancer or has a stroke or a heart attack or some other serious medical problem, the citizens have the right to know that the condition of the person they rely on has changed.

Sometimes it’s instructive to learn about famous people’s medical stories, as is illustrated in Barron Lerner’s book, When Illness Goes Public: Celebrity Patients and How We Look at Medicine. Openness about breast cancer by women like Happy Rockefeller, Rose Kushner and more recently Elizabeth Edwards (to name a few among many) have helped women move forward, from being ashamed of having BC to understanding about what it’s like to live with the disease. They helped other women to understand this disease, through their generosity of personal stories and experience.

The problem is that in our culture there’s so much openness about medical conditions, individuals may feel compelled to tell what’s happening if they have cancer or a recurrence or some other unfortunate medical event. But not everyone wants to do so, nor should they feel obliged.

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FDA Approves Adcetris for Refractory Hodgkin’s Disease and a Rare T-Cell Lymphoma

Late Friday afternoon, the FDA announced its approval, upon accelerated review, of a new drug, Adcetris (brentuximab) for patients with Hodgkin’s lymphoma that has relapsed after bone marrow transplant and for some patients with T-cell anaplastic large cell lymphoma (ALCL).Hodgkin's Disease pathology image shows classic "Reed-Sternberg" cell in center, W-C image

This interests me for a lot of reasons, among them that I used to work in the field of lymphoma immunology and spent some time in my life studying molecules like CD30, the protein to which the new antibody binds.

First, a mini-primer on the disease and numbers of patients involved:

Lymphomas are almost always tumors of lymphocytes, usually of T or B-cell type. In adults, around 80% of cases derive from malignant B lymphocytes; T-cell lymphomas form a varied minority. Approximately 66,000 people receive a diagnosis of non-Hodgkin’s lymphoma (NHL) every year in the U.S.; if a third of the 13,000 or so T-cell tumors are ALCL, there would be just over 4,000 cases of T-ALCL per year, of which only a fraction would require aggressive treatment (see below).

There are nearly 9,000 cases of Hodgkin’s lymphoma (a related condition, usually of B cells) each year in the U.S. Only a small fraction of the Hodgkin’s cases undergo bone marrow transplant and, of those, a smaller percent would relapse and need further treatment.

T-cell ALCL is a rare lymphoma subtype in which malignant T-lymphocytes express proteins including CD30, a complex signaling molecule of the TNF receptor protein family. Clinicians generally classify the disease based on whether it predominantly affects the skin, in which case it tends to be indolent, or if it affects internal organs like the bone marrow, liver and brain, in which case it tends to be aggressive and be unresponsive to standard chemo regimens like CHOP. The T-cell form of ALCL is unlikely to respond to Rituxan, a monoclonal antibody that binds to CD20 on B-cells.

Pathologists classify ALCL based on whether or not the malignant cells have a chromosomal translocation or subtler mutation involving the ALK (anaplastic lymphoma tyrosine kinase) gene. Presumably ALK (anaplastic lymphoma kinase inhibitors) are and will be tested in ALCL tumors with ALK mutations. Meanwhile, patients with ALK+ or ALK- variants seek better treatment options.

The new drug is a specially-designed monoclonal antibody that’s conjugated to a toxin. It binds a receptor, CD30, that’s found at the surface of activated T cells, normal and malignant, and on the most definitive Hodgkin’s lymphoma cells, aka Reed Sternberg cells.

As is the case for many cancer drugs, how Adcetris works is not perfectly clear. Prescribing information from the drug’s manufacturer, Seattle Genetics, says the antibody would be given every 3 weeks by intravenous infusion “until a maximum of 16 cycles, disease progression or unacceptable toxicity.”

The drug was developed by Seattle Genetics (Seagen.com) in collaboration with Millennium Pharmaceuticals, a pharma giant subsumed by Japan’s Takeda company. There’s a lot of money at stake.

Today Ed Silverman at Pharmalot reports on the price of the new drug:

…Seattle Genetics disclosed that the annual cost for Adcetris, which the FDA approved late last week to combat Hodgkin’s disease and another rare lymphoma, will cost $13,500 per dose. In clinical trials, patients received an average of eight infusions, which works out to $108,000 a year, which Xconomy reports was in line with several Wall Street estimates.

He wonders about the cost, and whether it’s justified. My view is that the drug’s use in T-cell ALCL seems reasonable because those patients have so few options. As for using it as a “salvage” drug in Hodgkin’s patients who’ve already undergone bone marrow transplant, a costly and toxic procedure, I’m less confident.

“Early clinical data suggest that patients who received Adcetris for Hodgkin lymphoma and systemic anaplastic lymphoma experienced a significant response to the therapy,” said Richard Pazdur, M.D., in the late-Friday press release. Dr. Padzur heads the FDA’s Office of Oncology Drug Products.

According to the press release, Adcetris was tried in a single-arm (non-randomized) trial of 58 patients with systemic ALCL. The tumors shrank partially or completely in 86 percent of patients. Their responses lasted 12.6 months on average. So far there’s been no demonstrated benefit in survival.

The data to support the drug’s use in Hodgkin’s patients after transplant come from a single-arm study of 102 patients who relapsed after autologous bone marrow transplantation. According to the FDA,  73 percent had a complete or partial response that lasted 6.7 months, on average, upon receiving the experimental drug. Again, there’s no demonstrated survival benefit, just a response rate reported by the agency.

There are over a dozen trials listed with ClinicalTrials.gov for Brentuximab Vedotoxin (SGN-35).

Meanwhile, we await FDA Commissioner Dr. Hamburg’s decision for Avastin in women with metastatic breast cancer.

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Mars Chocolate Company Advertises With Broccoli

MARS chocolate ad

The other day, over lunch, I was reading the Sept 2011 issue of the Atlantic and came upon this image on p. 37. According to the not-so-fine print, this full-page broccoli fix is sponsored by MARS chocolate, North America, website listed:


So we can find out about nutrition from the company that manufactures M&M’s, Snickers, Twix, MilkyWay and 3Musketeers.

Part of a trend –

The New Yorker recently ran a profile of PepsiCo CEO Indra Nooyi that almost persuaded me the super-sized soda-based conglomerate does the right thing in the healthy living department.

Kinda like Shell, Exxon and BP doing good work for the environment.

Got it?

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Reducing Costs by Better Integration of Palliative Care in Cancer Treatment

We’re up to point 9 on the list – and nearing the end – on Bending the Cost Curve in Cancer Care from the May 26 NEJM. The suggestion from Drs. Smith and Hillner is that doctors better integrate palliative care into usual oncology care.

The authors start this important section well:

We can reduce patients’ fears of abandonment by means of better-integrated palliative care. This topic is fraught with misunderstanding given the references to “death panels” during the recent debate concerning health care legislation…

Here they’re on target: Some patients think, mistakenly, that inclusion of palliative care in their treatment means their doctors are throwing in the towel. I’ve known some oncologists who think the same, who perceive palliative care as a last resort.

The truth is that palliative care, which aims to relieve symptoms, can be implemented at any point in the treatment of disease.

The authors go on to provide data that cancer patients who receive palliative care live just as long, or longer, than those who don’t, and that their medical bills are lower. The issue I have here is their choice of emphasis on a published study of the Aetna Compassionate Care Program in which nurses identified patients for palliative care by administrative claims, “thus bypassing the oncologist.” Evidently this strategy led to a doubling of hospice referrals and other possibly good effects.

Besides that the cited study was authored by employees of an insurance company, which I find unpalatable, the concept of having nurses do the referrals deflects the issue: that oncologists talk about palliative care with their patients, directly. Relying on nurses to carry out these conversations would, understandably, contribute to a sense of abandonment, even if the nurses do the job perfectly. A critical role oncologists is to communicate about treatment care options, part of the cognitive work considered in point 8 of this discussion.

But the main idea, that doctors should integrate palliative care into their cancer patients’ treatment planning, earlier, and as a supplement – and not a replacement – for potentially curative or tumor-shrinking strategies, is right on.

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Big Melanoma News: FDA approves Vemurafenib (Zelboraf)

Vemurafenib (PLX4032) structure, NCBI image

This morning the FDA announced approval of Zelboraf (vemurafenib) for treatment of some patients advanced melanoma. This is the second drug the agency has approved for this disease in recent months, after nearly two decades of a lack of new or effective therapies for melanoma.

Zelboraf is a pill. This small-molecule drug is thought to work by inhibiting an enzyme in malignant melanoma cells that have a specific BRAF mutation. A few months ago I wrote on this promising new drug, which goes by other names including PLX-0432.

The FDA also approved a companion test, cobas 4800 BRAF V600 Mutation Test, to check for the relevant mutation in patients’ tumors. Both the drug and the test are manufactured by Roche.

The other recently-approved melanoma drug, Yervoy (ipilimumab) is an antibody that’s given by intravenous infusion. This immune modulator, manufactured by Bristol-Meyers Squibb, works by a completely different mechanism: it blocks an immune system inhibitor, CTLA-4, and so “revs up” the body’s healthy immune cells in their capacity to destroy malignant melanoma cells.

Both new drugs are costly. A clinical trial, to test how the two drugs might work together in patients with the relevant BRAF mutation, should open for enrollment in September.

H/T to Sally Church @maverickny‘s early post on Pharma Strategy Blog.

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Notes on Kris Carr and Crazy Sexy Cancer

I’m half-tempted to put down yesterday’s new NYT Magazine feature on crazy sexy cancer goddess Kris Carr. Her blog was one of the first I found when I started ML, and it was the most popular link on my fledgling site until I pulled it, fearful of somehow sponsoring a too-alternative oncology perspective.

But I give Carr credit, sincerely: Crazy Sexy Cancer is a lot more appealing a title than, say, Medical Lessons. I’d read CSC, for sure, if I had a new diagnosis or, maybe, if I were alone and bored or suffering from a condition like chronic fatigue syndrome or insomnia and hadn’t gone to med school. Even for people who really have cancer, letting loose and being attractive sounds, well, like a lot of fun.

Kris Carr has played her C-card like a Queen of Diamonds. You go, girl!

So this morning I pulled a hard-cover edition of Cancer: Principles and Practice of Oncology, 7th Edition (2005; Lippincott, Williams & Wilkins; edited by DeVita, Hellman and Rosenberg) off my shelf and looked up Carr’s stated disease, epithelioid hemangioendothelioma. Being the old-fashioned woman that I am, I read about EH* in print. Only then did I discover a handy, unopened CD housed inside the cover of the “oncology bible,” as we used to call this text.

the editors, 'Cancer: Principles and Practice of Oncology,' Lippincott

DeVita and his colleagues classified this condition as a vascular tumor in a chapter on sarcomas, in a section on tumors that develop in smooth muscle. Now, at risk of boring my readers with the medical “scoop” on this strange and sometimes benign-behaving sarcoma variant:

As its name implies, epithelioid hemangioendothelioma is an angiocentric vascular tumor with metastatic potential…These lesions may appear as a solitary, slightly painful mass in either superficial or deep soft tissue. Metastases to lung, regional lymph nodes, liver, and bone are reported. Another pattern is that of a diffuse bronchoalveolar infiltrate or multiple small pulmonary nodules. This entity has also been called IBVAT…can also arise in the liver, often presenting as an incidental finding or as part of a workup for mild elevation of liver enzymes or vague abdominal pain. Multiple liver nodules are the rule. Although these lesions can metastasize, they usually run an indolent course. Liver transplantation has been performed…

This sounds scary, sure, but the bottom line is that this tumor falls into unchartered oncology territory because they’re so rare. As reported in the Times piece there are only 40-80 cases per year in the U.S. A reference in the textbook, above, leads to a 1989 report in the American Journal of Surgical Pathology. In that study of 10 cases, the authors describe an unpredictable course for the disease.

As told by Mireille Silcoff in the magazine, EHE comes roughly in two forms: one’s aggressive and one’s not. So what the oncologist at Dana Farber suggested – that she go about her life, and “let the cancer make the first move” – was a reasonable strategy, one that allowed them (patient and doctor) to find out, over time, what would be the nature of her particular EHE.

Carr lucked out: She has the “good EH” as Larry David might say. So far, at least, she’s enjoyed a  productive, enterprising  life with cancer. From the Times:

She was given the diagnosis in 2003 and rose to prominence with a 2007 documentary called “Crazy Sexy Cancer.” She subsequently wrote two successful books— “Crazy Sexy Cancer Tips” and “Crazy Sexy Cancer Survivor” — about her peppy, pop-spiritual approach to her disease, and she soon became what she sometimes describes as a “cancerlebrity” or, at other times, a “cancer cowgirl.”

Now she has a blossoming business. At the cafe, she laid it all out while sipping a coconut-vanilla chai with soy. Her blog postings are being syndicated, she has pending sponsorship contracts, her weekend workshops are thriving and she has provided one-on-one coaching sessions on Skype ($250 for 90 minutes). She also just bought a farm — 16 acres complete with two houses, a barn, a meadow and a forest…

Am I jealous? Sure, maybe, some…But I’d be hopeless on a farm.

Besides, she hasn’t received chemo, had limb-removing cancer surgery, undergone early menopause…She looks fabulous! And with that kind of cancer, maybe so would you.

The issue is that Karr runs a well-connected wellness enterprise. She sells a way of life, David Servan-Schreiber style, with the message that you can beat cancer and be well if you nourish your body and mind with the likes of 21-day cleansing diets, juiced Whole Foods and meditation-enhancing mala bead jewelry.

The danger is that readers and customers/followers may believe that her current well-being is due to her lifestyle choices. And that some people with the malignant form of EHE, whose emails she may not read, struggle with feelings of inadequacy and defeat.

So I’ve learned from Kris Carr: For one thing, I don’t think I ever saw a case of EH and she, through her story, persuaded me to look it up. Second, she’s a smart business woman, who’s turned her life around upon a cancer diagnosis. Third, (am undecided, ideas?)

And I’m taking careful notes. Let’s leave it with that, for now.

*This author prefers to call epithelioid hemangioendothelioma EH, but most sources use EHE, so I’ll abbreviate as do the sources or use my own style, accordingly.

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News on an Unusual Cancer Treatment by Heat in Surgery (Hipec)

There’s so much weird and exciting cancer news this week, it’s hard to keep up!

Double-kudos to Andrew Pollack on his front-page and careful coverage in the New York Times of the hyperthermic intraperitoneal chemotherapy (Hipec) technique that’s being used at some name-brand health care facilities to treat colon cancer.

First, he spares no detail in the Times describing the seemingly primitive, crude method:

….For hours on a recent morning at the University of California, San Diego, Dr. Andrew Lowy painstakingly performed the therapy on a patient.

After slicing the man’s belly wide open, he thrust his gloved hands deep inside, and examined various organs, looking for tumors. He then lifted the small intestine out of the body to sift it through his fingers…

….After about two hours of poking and cutting, Dr. Lowy began the so-called shake and bake. The machine pumped heated chemotherapy directly into the abdominal cavity for 90 minutes while nurses gently jiggled the man’s bloated belly to disperse the drug to every nook and cranny.

As a patient, I have to wonder, who’d sign up for this? And yet it seems they can’t complete a good randomized trial, for patients fear they’ll get the regular treatments only, without the Hipec. As an oncologist, I have to think, how can they possibly do a randomized clinical trial for this sort of method; the results would vary, enormously, from surgeon to surgeon, and from patient to patient – depending on the tumor load and responsiveness to heat, besides all the other tumor variables, even if the Hipec did help a patient or a few.

Pollack supplements the lead story with a shorter piece on hipectreatment.com, a website that obviously promotes the treatment but doesn’t reveal industry ties. According to his article, a competing site, HipecDoctor.com, lists doctors who do it (Hipec), but only includes those who use the site’s sponsoring company’s equipment.

At times like this, Nixon’s “war on cancer” takes on new meaning.

The business of oncology gets messy, on-line and in real patients’ guts. If you ask me, the Hipec approach might be labeled “alternative.” It’s certainly unconventional.

FDA, how do you classify this stuff?

HIPEC Surgery Featured on Grey’s Anatomy (KXLY news clip)

Hard not to contrast the Hipec news with the neatly-designed, high-tech and scientifically-detailed approach published yesterday in the NEJM for treatment of patients with chronic lymphocytic leukemia. That limited but fascinating report, of intense interest to cancer immunologists and gene therapists, serves mainly as proof of principle.

To find out more on Hipec, I intend to watch the segment of Grey’s Anatomy (see one of many related news clip here, scroll down) which may have popularized – and increased demand – for this procedure among desperate patients.

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Reducing Cancer Care Costs: The Value of Physicians’ Cognitive Work

We’ve reached what may be my favorite of the proposed ways to reduce cancer care costs, published in the NEJM by Drs. Smith and Hillner. Idea Number 8 is to realign compensation to value cognitive services, rather than chemotherapy, more highly.

What the authors are saying is that we’d save money if oncologists were paid more for thinking and communicating, relative to their compensation for giving chemotherapy. They write:

Medicare data have clearly shown that some oncologists choose chemotherapy in order to maximize income for their practice.<46,47> A system in which over half the profits in oncology are from drug sales is unsustainable.

They suggest that physicians’ compensation should go up, relatively, for time spent

  • referring patients for participation in clinical trials;
  • discussing orders for life-sustaining treatments;
  • considering advance medical directives;
  • talking about prognosis in family conferences.

I couldn’t agree more.

Take the clinical trials example. In my experience enrolling patients in clinical trials, it was a lot of work if you (the oncologist) wanted to do it properly: You’d have to read through the entire protocol; identify any potential conflicts of interest, look up any other protocols for which the patient might be eligible and (ideally) offer that as well, take the time to explain that it’s fine for the patient to not enroll – that there’s “no pressure” (subject of a future post: when patients feel that they should enroll in their doctor’s trial), answer all of the patient’s and a family member or friend’s questions about it, process the paperwork carefully…

And I’d add to the authors’ suggestions for compensation-worthy time spent:

  • going over pathology results, carefully and with an appropriate expert (a pathologist), and discussing the findings with the patient or designated proxy;
  • reviewing radiology images with appropriate specialists (x-rays, CTs, MRIs… comparing each with the previous studies) and sharing the results, as above;
  • checking blood work; abnormalities can be subtle; trends not obvious if results aren’t charted over time;
  • discussing the patient’s condition, periodically, with other doctors such as the internist (or pediatrician), cardiologist, pulmonologist, surgeon, etc.
  • researching relevant published studies and case reports for puzzling clinical situations (using Google, Medline, a real library, maybe calling an expert at another medical center…)
  • communicating with patient about the condition, more generally (not only about end-of-life issues) – such as explaining  a tumor’s known or unknown causes, treatment options, genetic and other implications of a cancer diagnosis.

Bottom line:

When oncologists earn more money by prescribing treatments like chemotherapy, there’s a conflict of interest and a tendency to give more treatment. If oncologists’ salaries were set based on a case load, or time spent taking care of patients that includes cognitive services – thinking and communicating – patients would get better care and less unwanted treatment.

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Breast Cancer Avastin Update

This afternoon Ed Silverman of Pharmalot reports that Roche has proposed a compromise to the FDA over Avastin’s use in women with metastatic breast cancer. The drug would be approved for use only in combination with paclitaxel (Taxol), for which the data are strongest, and with special warnings.

He writes:

The deal includes revised labeling in which Avastin would be recommended only for patients displaying “aggressive disease” and who have the fewest treatment options. Roche also suggests a Risk Evaluation and Mitigation Strategy, or REMS, as well as a Medication Guide.

This sounds like a reasonable solution. As I have considered elsewhere, the FDA commissioner’s decision is pending.


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