Taxol Dosing – new study

Wikimedia Commons image

Paclitaxel was originally isolated from the bark of the Pacific yew tree, where it is synthesized by endophytic fungi.

“The addition of new chemotherapy drugs has not improved outcomes. Thus, we need to give the active drugs in the best way,” says G. Thomas Budd MD of the Cleveland Clinic. Dr. Budd reported a very interesting study comparing two dosing regimens of Taxol (paclitaxel) at ASCO 2013, this year’s annual meeting of the American Society of Clinical Oncology, which took place from May 31st to June 4th.

I was particularly drawn to this abstract because Taxol caused what was probably the most unpleasant experience I have had to date on chemotherapy. Oh, I lost four kilos a treatment on the AC schedule, but vomiting could be controlled. But Taxol… Taxol quite literally took my breath away. My chest hurt and I was coughing and gasping for air. The friend who had accompanied me to that first dose, a nurse herself, started me on oxygen and went for the chemo nurse. They put me on steroids and something else that made me sleep. From then and for the rest of the series of Taxol treatments, I received a bag of IV steroids before the treatment, then something that made me sleep, then finally the Taxol. It was not fun.

So it was interesting to read this abstract. I won’t go into the details of the protocol, but you can read about it at the links I’ve provided below. The part that concerns us was the comparison of two dosing regimens for Taxol: the traditional “dose-dense approach” given every two weeks that was developed at Sloan-Kettering, and a lower dose given weekly.

Discussing the conclusions of the survey, Dr. Budd said: “Either regimen can be selected on the basis of efficacy. So in practice, treatment can be selected based on other considerations, such as toxicity.”

Toxicity of cancer drugs is graded on a scale called the Common Terminology Criteria for Adverse Events (see National Cancer Institute Wiki FAQ on the CTCAE) that ranges from  0 (no adverse effect to 4 (life-threatening adverse effect). (Grade 5, death, does exist on the scale, but was not a factor in this study). The study found that both regimens had grade 3/4 toxicity, but that the “toxicity profile” differed between the two. The dose-dense protocol led to more allergic-type reactions, whereas the lower weekly dose showed more hematological toxicity.

The study concluded that 12 weeks of low-dose Taxol produces less overall toxicity than  six cycles of dose-dense treatment (one cycle every two weeks).

What are the implications for me? If my oncologist should suggest putting me back on Taxol (it has been shown to have some efficacy in stage IV breast cancer), I would definitely ask about the weekly schedule. (It may not be possible in my case due to chronic neutropenia, but it’s worth investigating.)

Notes:

It should be remembered that these findings were presented orally at ASCO and have not yet been published in a peer-reviewed journal.

The study was funded by the (American) National Institute of Health and Amgen.

The abstract, which was presented orally, can be read online here and there is a discussion of it by Medpage Today staff writer Charles Bankhead here.

Pain is in the brain

This image shows regions of the "neurologic pain signature," a standard map that can be applied to individuals who may be feeling pain. The map was developed based on heat pain applied to participants' forearms. Activity in yellow areas is predictive of higher levels of pain, and activity in blue areas is predictive of lower levels. (Photo: Tor Wager, University of Colorado, Boulder, via AP)

Pain is much on my mind lately. As recently as last November I wrote a post (Pain) in which I talked about my reluctance to use narcotic pain relief. Recent readers of Telling Knots will know that I have since agreed to take the stuff in spite of my objections. I still hate it and I still take as little as possible as infrequently as possible.

I wish there was a non-narcotic medicine for moderate to severe pain, and every now and then I spend some time on PubMed looking for answers. I stumbled across some fascinating findings today.

The image above and its caption are from USA Today online article from April 10, 2013. (Please hover over the image with your mouse to read the explanation and photo credit.) This very exciting research used functional Magnetic  Resonance Imaging (fMRI) to develop a “neurological signature” of physical pain.

A free preview of the original article in the New England Journal of Medicine can be see online here.

It is very, very early days and this research consists of four studies with a total of only 114 healthy subjects in the laboratory. Even so, the possibilities are tantalizing. The USA Today article quotes lead author Tor Wager: “”Many people suffer from chronic pain, and they’re not always believed. We see this as a way to confirm or corroborate pain if there is a doubt.”

The novelty of this study is not simply producing an image of what happens in the brain when pain is perceived, but in producing a combined signature that can actually measure pain. Furthermore, the researchers were able to distinguish physical pain from social or emotional pain.

As I said at the beginning of this post,I wish there was a non-narcotic medicine for moderate to severe pain, and obviously, I am not the only person interested in this: the study was partially funded by the (United States) National Institute on Drug Abuse, for example.

Aside from this being very cool research that may have many fascinating applications in the not-too-distant future, there is one aspect of it that I immediately hooked into. As Dr. Allan Ropper told USA Today, “This is beginning to open a new wedge into brain science,” Ropper said. “There may be completely novel ways of treating pain by focusing on these areas of the brain rather than on conventional medications which block pain impulses from getting into the spinal cord and brain.”

And that made me do a happy dance. Can you imagine how wonderful it would be to be able to treat pain (the whole pain, and nothing but the pain) without the side effects of narcotics? I know this is far in the future and I may not live to see it, but just the fact neuroscientists are working on it makes me very, very happy.

Seriously, MD Anderson Cancer Center?

Dr. Ronald A. DePinho, President of MD Anderson Cancer Center

Today it is my great pleasure to reblog this post from the American neurologist who blogs at Doctor Grumpy in the House. (It is a great blog with humor, honesty, humanity and all kinds of good stuff that does not necessarily begin with H. You should read it.)

This post, originally titled “Things that make me grumpy” is about the money troubles of the iconic MD Anderson Cancer Center. Due to these misfortunes, the Center’s president, Dr. Ronald DePinho, has instituted “austerity measures” because, he says, “For most of fiscal year 2013 our operating expense has exceeded our operating revenue – meaning that we’ve spent more than we’ve made from providing patient care services.”

Read Dr. Grumpy’s post to find out where one and a half million dollars of that revenue went.

Thank you, Dr. Grumpy, for permission to reblog your post.

Times are tough for doctors these days. No one gives a shit, so I’m not elaborating further.

But even big institutions are affected. Take, for example, the venerable MD Anderson Cancer Center in Texas. This giant of oncology has recently been having financial issues, so much so that its president, Ronald DePinho, sent out this e-mail to employees 2 weeks ago:

“For most of fiscal year 2013 our operating expense has exceeded our operating revenue – meaning that we’ve spent more than we’ve made from providing patient care services.”

He went on to say that because of this shortfall MD Anderson is suspending merit raises and slowing its hiring rate. This is what they call “austerity measures.”

Now, every concerned CEO in America has been saying stuff like this, so why am I singling out Mr. DePinho?

Because.

At the same time Mr. DePinho is preaching financial restraint for his cash-strapped institution, he’s used $1.5 million of its capital funds (which come from investment income, donations, and patient revenue) to build a 25,000 square-foot (2,322 square meter) office suite for Dr. Lynda Chin at the institution.

Who just happens to be his wife.

Really. I am not making this up.

Dr. Chin is the scientific director of MD Anderson’s Institute for Applied Cancer Science. How this justifies her having an office suite that is 10 x larger than the average American home is beyond me. According to the institute it’s to “provide an appropriate meeting space with high-level industry decision makers and support a new suite in computational biology.” Translation: By using a lot of syllables we’re hoping you’ll ignore what’s really going on here.

And no, I have no idea what “computational biology” is. Maybe that’s why my entire office is 1,250 square feet, including the john.

According to an itemized expense report (obtained by The Cancer Letter under the Texas Public Information Act) this ginormous office has $28,000 worth of chairs, sofas, and tables. They also spent $210,000 on fancy translucent glass walls, which required them to get a special permit from the University of Texas. By comparison, the Grumpy Neurological Emporium has used furniture (valued at $948 total), and plain old painted drywall.

So, if you donated money in a loved one’s memory to MD Anderson hoping they’ll find a cure for whatever cancer killed grandma, there’s a reasonable chance your hard-earned dollars went to pay for… upscale furniture and fancy glass walls in an office bigger than your house.

I’m going to close with another quote from Mr. DePinho, found in the same e-mail I quoted earlier about the austerity measures MD Anderson will have to take to survive:

“If we don’t make changes now, we potentially will find ourselves in a crisis that will force us to take drastic measures that could hurt our ability to meet our mission… [all will] have to share sacrifices.”

Well, almost all.

Thank you, SMOD!

Breast Surgery News

Aside

With thanks to Dr. Deanna Attai, a California breast surgeon and the new  Secretary-Treasurer and member of the Executive Committee of The American Society of Breast Surgeons, who posted this on her Facebook page, I’d like to draw your attention to this article in the Seattle Times, by Marilynn Marchione, AP Chief Medical Writer:

Women have new options for breast cancer surgery

Treating breast cancer almost always involves surgery, and for years the choice was just having the lump or the whole breast removed. Now, new approaches are dramatically changing the way these operations are done, giving women more options, faster treatment, smaller scars, fewer long-term side effects and better cosmetic results.

Please read the rest of the article here.

The Komen Organization in Numbers and Words

komen total exp

Figure 1. Total expenses of the Komen organization for the year ending 31 March 2012.

I love the Internet! With thanks to my friend GG, a stellar webcomber, I have been spending the last couple of days studying the most recent independent audit of the Susan G. Komen Breast Cancer Foundation, Inc. The audit is available to all as a PDF at that link.

First, the numbers

The Komen financial year runs from the first of April through March thirty-first. The most recent independently audited annual financial statement dates from March 31, 2012, and this post is based on those numbers.(*)

komen totals

Figure 2. Gross breakdown of Total Expenses from Figure 1.

The good news first. Komen spends a relatively small portion of income on support services–about 19% of total expenses(the blue slice of the pie at the left). These support services expenses consist of fund-raising costs ($52,118,804 or 69%) and general/administrative costs ($23,064,504 or 31%).

The largest portion of Komen income, about 81%, is very appropriately spent on program expenses (the green slice). I am particularly interested in taking a closer look at how that $318,281,722 is spent.

Komen program

Figure 3. Breakdown of program expenses.

There are four categories of program expenses: Research (21% of total program expenses), Public Health Education (44%), Screening (16%) and Treatment Services (8%). The pie chart at the right shows the breakdown.

The lion’s share, of course, is spent on “public health education”. I assume this means awareness campaigns. About a fifth of program expenses are invested in research, approximately the same amount in health screen and treatment services.

Now the words

The  Komen organization was founded in 1982. At that time it made enormous sense to make massive investment in public education and awareness, to dispel the fear that surrounded the word “cancer”. Young people today would have trouble understanding how terrifying the illness was; the word was rarely even pronounced aloud. People were too frightened to examine themselves and sometimes even to go to a doctor if they suspected something. After all, the reasoning went. It’s a death sentence whether I get treated or not.

So much has changed in the more than thirty years since that time. Cancer is now seen as a serious and treatable illness, rather than a death knell, and even metastatic cancer is approached as a chronic disease. Most women in the West have been taught about breast self-examination and breast exams are a regular part of the preventative medicine protocols of hospitals, clinics and insurers.

Moreover, today’s medical thinking and standard of practice is rethinking its approach to mammography, moving toward starting later and repeating less frequently in most cases. The American Cancer Society’s recommendations now call for:

  • Yearly mammograms are recommended starting at age 40 and continuing for as long as a woman is in good health
  • Clinical breast exam (CBE) about every 3 years for women in their 20s and 30s and every year for women 40 and over
  • Women should know how their breasts normally look and feel and report any breast change promptly to their health care provider. Breast self-exam (BSE) is an option for women starting in their 20s.

Is the Komen mission still relevant in 2013?

I’d prefer to answer a slightly different question. Do we still need a large, well-known breast cancer charity in 2013?

Yes, of course. But as the world has changed since 1982, I suggest that the Komen organization’s mission should change. In a country where fewer and fewer people have access and the means to pay for medical care, I suggest that Komen is well placed to increase the proportion of income spent on treatment services. Perhaps individual treatment grants or matching funds or helping to pay for the operation of breast clinics could be considered.

I suggest that more of the organization’s income should be invested in research, both clinical research and basic research. The more we know about cancer, the better equipped we will be to treat it, perhaps even prevent it. I don’t have a personal stake in this; today’s research is not going to benefit me. But think of the generations it could help!

My proposal, then, would be more of a three-piece pie: a third of program expenses to public health education, a third to research and a third to treatment services. What do you think?

=====

(*)The pie charts were made with the free Create-A-Graph tool available in the Kids’ Zone of the American National Center for Education Statistics.

Discrepancies in totals are due to rounding off or to my own arithmetic incompetence. The original figures are can be seen at the link to the independent audit in the first paragraph of this post. I welcome comment and correction.

“Metastatic work is a waste of time.”

bullying1With thanks to Nancy Stordahl of Nancy’s Point for posting it on Facebook, I’d like to draw everyone’s attention to a spot-on article on Salon: The ultimate cancer taboo: Sometimes it kills you by Mary Elizabeth Williams.

If anyone wonders why people with metastatic cancer sometimes (often) feel like the red-headed stepchildren of the cancer world (no offense intended to redheads or stepchildren), this article will make it clear.

Contemporary cancer gets couched in the language of cheerleaders. Even a generation ago, the mere word “cancer” seemed a certain death sentence; today, in contrast, it’s an opportunity to talk about battles and fights and hope. It’s something to be bravely dealt with – having cancer automatically designates a person a “warrior.” The disease is then referred to only at occasional “awareness” opportunities, preferably with a tasteful ribbon.

But people with metastatic cancer don’t follow the tidy, cheerful narrative. They don’t necessarily fit the inspirational survivor mold. And so they’re ignored.

So begins the article. She continues with some eye-opening figures and quotes Danny Welch, chairman of the University of Kansas Cancer Center, who told Peggy Orenstein: “A lot of people are under the notion that metastatic work is a waste of time.”

Let me tell you how I heard that.

Premise: Research into the causes and potential treatment of metastatic disease could lead to people like me living longer.

Premise: Such research, a lot of people think, is a waste of time.

Conclusion: A longer life for people like me is a waste of time.

Yes, I do take it personally. Wouldn’t you?

Williams goes on to talk about her own experience with Stage IV melanoma and that of Lisa Bonchek Adams, a well-known breast cancer blogger, and offers this very important suggestion:

So if you’ve ever considered whipping out the talk about miracles or just keeping a positive attitude or some other unhelpful tack in a transparent attempt to keep your own terror of death at bay, that’s actually a pretty crappy thing to lay on a person with a serious disease. Please don’t do that.

This is not a long article, and it is well worth reading. I’ve only skimmed a few of the high points. Please do click on the link (here it is again) and read it.

I’ll end by making my own the words with which Williams closes her article: “Yes… I’m still right here.”

Long-term Role of SERMs in Preventing Recurrence of Breast Cancer

Estradiol molecule

Estradiol molecule

A meta-analysis published in The Lancet looked at the role of SERMs (Selective Estrogen Receptor Modulators) and found that they do indeed play a role in reducing incidence of breast cancer recurrence for as many as ten years after initial diagnosis and treatment, with the greatest benefit in the first five years.

SERMs are drugs like tamoxifen that act on estrogen receptors. Estrogen receptors are proteins inside cells that are activated by estrogen and can then move to the cell nucleus and bind to the DNA. This can cause creation of tumors. I do not have the figures at hand, but I believe that around two-thirds of breast cancers are estrogen positive; that is, associated with over-expression of estrogen.

Different SERMs affect estrogen receptors in different ways, but essentially they either cause or block cell activity in different kinds of tissue (that’s the “selective” bit). The following table is from Wikipedia, where interested people can find relatively non-technical articles about some of these subjects. (Just please remember that I did say “relatively”.)

Name Uses Effects/location
clomifene used in anovulation antagonist at hypothalamus
femarelle managing menopause symptoms, osteoporosis agonist at brain and bone
ormeloxifene contraception agonist at bone; antagonist at breast and uterus
raloxifene osteoporosisbreast cancer agonist at bone; antagonist at breast and uterus
tamoxifen breast cancer agonist at bone and uterus, antagonist at breast
toremifene breast cancer
lasofoxifene osteoporosisbreast cancer, vaginal atrophy agonist at the bone, antagonist at breast and uterus

The article, “Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data” by Cuzick et al., is available at The Lancet as an early online publication dated today, 30 April 2013. (Free registration is required to view the article in full; a summary can be seen without registration.) It looked at four SERMs:  tamoxifen, raloxifene, arzoxifene, and lasofoxifene in various studies.

A less technical description of the study is available online at MedPageToday in “SERMs Still Have Value for Breast Ca Prevention” by Charles Bankhead, who writes:

In spite of the demonstrated efficacy, SERMS continue to be ignored by patients and primary care physicians alike, “mainly because of concern about toxic effects and perceived unfavorable balance between benefits and harms,” the authors noted.

“Unfortunately, at the present time, none of these drugs are being actively marketed for breast cancer prevention,” they said. “Our longer-term assessment shows that the benefit-harm balance is now more favorable than that calculated for short-term follow-up, and, in view of this new evidence, assessment of these drugs, especially lasofoxifene, should be continued.”

As with any medical treatment–and perhaps even more so with cancer treatments–possible adverse effects must be weighed against potential benefits. I am a relatively savvy patient, but like everyone else I am dependent on my oncologist to interpret these and other findings in terms of my own history and current state of disease. Nevertheless, the results seem encouraging–if only as research that can help lead to treatment that will reduce the incidence of breast cancer recurrence.