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Published on 22 August 2007

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Getting the dose right

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Greetings blog readers and welcome to the latest instalment of our oncology pharmacy blog. Summer is almost over in England – although some would say it never began. At the same time, Italy and the Balkans have been suffering heatwaves.  There is often the sense that the grass is greener on the other side. However, at the moment, one side is more like a mud sump, where the other is scorched earth. Still at least it’s not the Caribbean!

I have just returned from my annual outings and am slowly trying to get back into the work frame-of-mind again. I have now reset all my passwords which had expired, turned off my out-of-office assistant and am slowly ploughing my way through the 500 or so emails I received whilst I was away. Who said that computers would make working lives easier?

One of the emails I received was a very interesting piece of work from the Cancer Network Pharmacists Forum, UK, which was looking into dose banding practices from around the UK. One of the first things that struck me when looking into this was the practice of how doses were calculated prior to dose banding. It appears that there is still no consistency – at least in the UK – in how people calculate body surface area (BSA). The standard formula for most institutions in Canada is the Mosteller formula, which is in my opinion also the easiest to use.

√[(Ht x Wt) / 3600] = BSA

It is also based on more sound principles than the other international favourite Dubois and Dubois. Dubois and Dubois made several assumptions, such as that the right side of the body is symmetrical to the left. Their measurements were crude, limited by the scientific instruments of the day. Their subject numbers were small. They used only nine people to construct their formula, some of whom were amputees. Admittedly, considering the constraints they produced a fairly accurate equation. But in 1970, Gehan and George challenged the use of Dubois and Dubois, concluding it overestimated BSA by 15% in around 15% of patients. I’ve included the references below for those of you who are interested in looking into this further.

The point of this however is not that we are using a crude formula or an accurate and simple formula. The point is that we are dosing patients with chemotherapy such that in another part of the country, a patient with the same height and weight may conceivable receive a significantly different dose of chemotherapy. Of course there are some therapeutic indications where this would not cause a great difference in therapeutic effect, as the differences are, on the whole, likely to be small. But in certain haematological indications where the maintenance of dosage intensity is paramount and where greater efficacy has been shown with larger doses, there ought to be consistency to allow the results of trials to be reproduced. Otherwise, how do we know that our patients are being treated effectively?

Of the hospitals in the survey that have deviated from Dubois and Dubois (which is the formula used on the slide-rules the pharmaceutical companies provide for us) more than 60% opted for the Mosteller formula. Worryingly 2% of respondents stated they were not sure which formula they were using. It seems therefore that once it has been considered, the Mosteller formula is the most accurate and the easiest to use. In the UK a body such as the National Institute for Clinical Excellence needs to make a decision. Hopefully in mainland Europe there will already be some standards in place.  I’m keeping my fingers crossed! If you are as passionate about this as I am, please post a reply to let us know what is happening in your countries.

David


1.  Mosteller RD. Simplified calculation of body-surface area.  New Engl J Med 1987;317:1098.

2.  Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known.  Arch Intern Med 1916;17:863-71.

3.  Gehan EA, George SL. Estimation of human body surface area from height and weight.  Cancer Chemother Rep 1970;54:225-35.

 



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