Odds are that you have been faced with a similar dilemma. I have a new patient, not yet 40 years old, who was recently diagnosed with bilateral locally advanced breast cancer. Staging scans did not reveal metastatic disease. I recommended systemic therapy with doxorubicin, cyclophosphamide, a taxane, and trastuzumab followed by endocrine therapy. Pretty straightforward, right?
Here’s the problem: she is 61 inches and weighs 300 pounds. That translates to a body surface area (BSA) of 2.42 and a body mass index (BMI) of 56.7.
How should I dose her chemotherapy, given her morbid obesity? I sought advice from many of my medical oncology colleagues, all of whom I respect greatly. There was a true lack of consensus. A few said to “cap” her BSA at 2.0 m2. Others said to use ideal body weight. One colleague suggested that I treat her at full dose but to divide the anthracycline dose over two days.
Appropriate dosing of obese patients is a problem that oncologists are increasingly facing. More than 60% of Americans are overweight, obese, or morbidly obese. Some studies have shown that obesity increases the risk of developing certain cancers. Therefore, it is imperative that oncologists know how to optimally treat obese patients with cancer.
In my view, ASCO’s new guideline about appropriate chemotherapy dosing for adults with cancer is one of the most clinically useful treatment guidelines I have ever read. This comprehensive document contains an exhaustive systematic review of the literature and makes clear specific recommendations for optimal treatment of our obese patients based on evidence. The panel recommends full weight-based chemotherapy dosing, particularly when the goal of treatment is cure. With several exceptions, the use of fixed-dose chemotherapy is rarely justified. The panel explicitly states that there are no randomized trials of full weight-based chemotherapy vs. nonfull weight-based chemotherapy but based their recommendations on large observational and retrospective studies. It’s a great guideline, and I’d urge every oncology provider to read it.
Phew…Now I know what to do with my patient!
Comments
Richard S. Leff, MD, FACP
Apr, 03 2012 3:40 PM
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 underdosing obese patients 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 much smaller. (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 and are rarely questioned by most of us. Perhaps we can spot the next system-wide mistake before we have been doing it for 30 years.