It’s always a shock when something we were taught in our training and used for years turns out to be wrong and even harmful. The latest, that we have been under-dosing obese patients with chemotherapy for decades, is not the first or the last in this category but it certainly involves a lot of patients who were treated in the past 30 years. When I was a fellow I was carefully taught that total body water content did not increase linearly with BSA in very obese patients so that BSA overestimated the true volume of distribution. As a result, we believed that doses should be reduced from the ones based on actual BSA, particularly in obese bone marrow transplant patients where the therapeutic index was particularly small. (In fact, if my memory serves me correctly, I think there may have been a question about just that on my Oncology boards.) Good theory if only there had been data to support it.
But there were other conditions 30 years ago that made the decision in the direction of safety rather than efficacy reasonable. Back then most of our therapies were given with palliative intent with many fewer curable patients treated. It was much easier to rationalize doing no harm when the upside of therapy was much less than it is today and the downside related to toxicity was greater. Our options to treat the complications of our therapies were much more limited. Hospitalization for 7 to 10 days with IV antibiotics for neutropenic fever was not uncommon as we had not yet seen the benefits of growth factor availability. In addition, IV antibiotics which routinely included aminoglycosides carried more risk, particularly of renal damage. Blood products were not as safe as they are today and anti-emetics would have to be described as rudimentary in comparison to our tools today. So we live and we learn.
Aside from changing our dosing for obese patients what lessons have we learned from this issue? We need to develop better ways to examine the systems and rules we use every day in our decision making and we need especially to regularly question the paradigms that drive our specialty, were taught to us by our mentors and are rarely questioned by most of us. Perhaps we can spot the next mistake (opportunity for major improvement in current vernacular) before we have been doing it for 30 years.
Rich Leff, MD
Conisus 
As a very large man standing a healthy 6’11” I often wonder about how relevant medical research is to a patient of my stature. I have often had HCPs stumped by simple questions like if I need to eat double the RDA of calories (approx. 3600) should I also double Vitamin A, B, etc.?? I still don’t have that answer.
This situation of having under-dosed obese patients with chemotherapy for years falls into this same category of maybe something called “medical outliers”. It certainly isn’t the medical communities fault as understandably it works to bring wellness to as many people as possible, which often can leave out these outliers. Hopefully as EMRs become more of a reality as we find smart ways to protect individual privacy while providing aggregate data to business analysts with better big data visualization technology, we’ll start to find these trends faster in “outlier” groups.
Growing up in Montana I could not easily buy shoes above size 12. Today with the internet and an ability for corporations to reach enough of a niche audience to warrant a business model by breaking the bounds of geography large shoes are no longer a problem. Hopefully, the medical community can follow along by joining seemingly disparate groups on different markers and discover revelations like this one and create markets while improving healthcare not only for the masses but also the outliers, like myself.
I just read this week that redheads take more anesthesia for dental surgery. This is just another crazy outlier that we must have lucked upon. Hopefully in the future we will strategically draw the facts out of the data, instead of randomly discovering them as now our collective knowledge is stored on paper in file cabinets stagnant and not very useful compared to it’s future potential.