I am so unsympathetic to malpractice "reform."

and oh yeah, thank you for documenting one more example of the war on women.

That fat women are just supposed to roll over and die, for having the temerity to exist, and inflicting their flubby selves on the rest of us? If you encourage them in expecting sound medical treatment, next they will want to walk outside without being catcalled and insulted, and we can't have that.

as within the past year my son's stepmother died of ovarian cancer.
I'm right up there with "malpractice reform" as a reason to get out the pitchforks and torches.
the system sucks, and it isn't getting any better, and all our pretty words don't help when we're not addressing the real issue.
People need good treatment.

It is really great you wrote this post. You just have to document this trash incident by incident.

This study was on women, but the improper practice of capping dosage is widespread and doesn't depend on the patient's gender; men as well as women over and under "ideal" weight are too often given less than maximally effective doses.

Scarier still, the recommendations now representing "best practice" that adjust dosage for either BSA or body weight are both inaccurate for patients outside the "normal" bounds. What should be done is to dose to blood volume, to ensure the proper concentration of chemo for maximal kill of malignant cells while staying just this side of fatal toxicity. Unfortunately, there are no processes for either ordering or paying for the simple and cheap test needed to establish blood volume.

Epithelial ovarian cancer is a horrible disease with a poor prognosis. As the study you cite shows, the survival and recurrence rates improve with higher more appropriate doses but not by much. We still have along ways to go to understand this disease.

Briefly, on obesity and cancer. The issues aren't really clear at all regarding survival and recurrence or even incidence. A lot of things are going on in people with greater than "average" weight-to-height ratios, and only some of them are drivers of increased morbidity. Certainly, diabetes as either a cause or a consequence of higher weight makes recovery from surgery more difficult, while abdominal weight gain in particular raises the risks of complications from surgery and anesthesia. These aren't opinions but fact, and a caution from a physician about them is only responsible. We all make choices about tradeoffs with risk, as I do when I ride a motorcycle off-road without a helmet, but they should be informed choices. (For myself, I prefer to die from brain injury rather than survive as a quad.) Not that it helps, but people who are significantly underweight are also at higher survival and complications risk.

Caveat: None of what I say should be taken to mean that women's health issues have not been under-represented in either research or treatment; they surely have. The answer, I think, is fairly straightforward; more women physicians are needed, especially more women surgeons - no reason at all why the whole profession shouldn't be 50/50. Medicine is a field that is stuck well back in the Middle Ages when it comes to sexism, and we as a nation suffer greatly as a result.

The whole health care/denial system is far less than optimal, in so many ways, with more people dying prematurely now in this country from improper treatment - mostly medication errors including chemo - than from no treatment at all. We need more and better health care. I am a huge supporter of the move called for by Obama towards modernizing records and improving alerts for treatment errors; it won't do us much overall good to simply bring everyone into a deeply flawed system.

faster and more efficiently than the current system. I know many many doctors and sat in hospital admin meetings. It was never the case where the doctors sat around trying to deliberately kill patients. If you understand clinical trials, you would know that there is rarely a weight subgroup and that subgroup statistics are much less significant. Only recently have differences in ethnicity been discovered to be involved in some drug interactions because that wasn't always a variable either.

If you had the data available for everyone's drug interaction (within privacy constraits), you can have researchers mine the data to find a lot of missing interaction trends. Believe it or not, not all these facts are missing for malicious reasons.

for the best diatribe delivered against the greedy a**holes.

What should her prize be?

I agree with GQM and Bringiton. I've got an incurable cancer (metastatic leiomyosarcoma), and I work with patients and doctors. Finding solutions is easier if you understand the problems. The problem is not that all oncologists are greedy, incompetent jerks who don't care about their patients.

Here's an example on clinical trials: A medical oncologist in gynecology came up with a protocol that combined two chemo drugs to get a better response in uterine leiomyosarcoma. This exact protocol was tested in clinical trials for several years, and it was more effective than any other chemo combo that had been tested. Now, docs are testing to see if a lower dosage may be just as effective, and less likely to kill patients. Someone might say doctors were stupid and reckless not to try a lower dosage before in clinical trials. But docs went with what seemed to work for the most people, rather than risk not helping the patient at all.

we've had, and will continue to have, I'd bet, our incongruent points of view.
but your point about medical practitioners' 'black humor' being similar to that of firefighters, cops, soldiers and veterans is well-taken.

No, what I'm on about is that using outdated information to reinforce prejudices and REFUSING to acknowledge that the person in the room at the time is not a data point in an algorithm results in needless death -- often painful and lingering -- in direct violation of the principle, "First, do no harm."

And yes, the diatribe will continue every time fresh evidence of that stripe of imbecility triggers it.

Now, about this "blood volume" thing: tell me more. Typically it's 4-6 pints per adult, yes?

Blood volume varies considerably from one person to another and indirect measures like weight and body surface area are poor predictors. Here are averages for different ages. The “typical” value of 70 milliliters per kilogram (ml/Kg) shown for adults is a rough measure at best. (Modern times, metric measurements; nobody working with blood uses pints and pounds anymore.)

As the articles you referenced discuss, Body Mass Index is considered a more accurate guide than weight alone. But the BMI calculation can be misleading in several ways.

Muscle tissue is denser than fat cells, and also has more blood volume per gram of tissue, so a 5’10” 250 lb couch potato will have a very different blood volume than a 5’10” 250 lb NFL running back. Patients with certain diseases, such as chronic cardiac failure, pulmonary hypertension, cirrhosis and portal hypertension, will have expanded blood volumes (hypervolemia) while patients who have been vomiting or not getting sufficient fluids can develop unusually low blood volume (hypovolemia). Deviations from “normal” blood volume can result in chemotherapy treatment that is either unnecessarily toxic or ineffective.

More dramatic even than fat/muscle ratio or comorbid disease is the effect of red cell concentration. Many drugs are carried only in the plasma and largely excluded from red cells. A patient with a hematocrit (red cell fraction) of 45% would have a plasma volume of 38.5 ml/Kg [70 ml/Kg blood x .55 = 38.5 ml/Kg plasma] while a patient with a hematocrit of 30% would have a plasma volume of 49ml/Kg. Given the same dose of a drug, the actual plasma concentration would be quite different.

Here are a couple of graphs to help illustrate the point. With chemotherapy, the concentration of a drug is critical; too low and cancer cells will not be killed, while too high a concentration can seriously damage or even kill the patient. The distinction between those two concentrations, high enough to kill target cells but not so high as to kill the patient, is called the Therapeutic Range and for chemotherapy agents that range is quite small.

The goal then is to reach a therapeutic level without venturing far into toxicity. Some overshoot is inevitable, and so chemo patients commonly lose their hair and become anemic due to toxic effects. This is what drug plasma levels would look like in a “normal” patient who was properly treated with a “standard” dose:

But when that same “standard” dose is given to patients with a higher or lower than normal plasma volume, you can see that either the patient is not effectively treated (as in a segment of the cases considered in the article you cited) or given what may be unacceptably toxic concentrations:

It was to avoid the possibility of reaching highly toxic levels that doctors adopted the practice of capping chemotherapy doses – they were earnestly, if naively, trying to respect the dictum of “First, do no harm.”

It may seem outrageous to you, but the extent of ignorance among medical professionals is greater than it should be. The old days, when a physician could carry everything they could use in a small satchel, are gone. Today, the scope of knowledge is far greater than any one person can encompass and the “tool kit” is so extensive that even highly trained specialists don’t know everything up-to-date within their own specialty.

Generally speaking, the notion that drug administration in adults should be individualized is unappreciated. While for most drugs this may not be particularly important, with chemo the dosage is highly critical and the consequence of imprecision is premature death. A specific field of medicine, pharmacokinetics, has been developed to deal with the issue. Now widely used for treating infants, it is not recognized as important by most physicians who treat adults including oncologists.

While techniques for determining blood volume with dyes such as Evans Blue have long been known and are well established, concerns about health effects limit their use. A new approach has received FDA approval, but so far as I know there are no reimbursement codes that will cover payment for its use. Without reimbursement for individualized blood and plasma volume determinations and absent increased education of the physician community on its importance, I do not foresee widespread improvement in the precision of cancer chemotherapeutics.

Additional reference information about blood volume and BMI calculations, as well as “lots of other goodies.” Enjoy!

PS: Thanks for not doing the red mist thing; much appreciated.

Why not in people?

I always found it strange that with things like antibiotics that often the same dose was given to a 120 lb woman as a 200 lb man. That seems to be odd to me, unless I just don't understand the logic.

Chemotherapy should be conducted with more precision than it is; but then lots of things should be done better than they are.