unfortunately a trip to The Metric System SchoolHow an

unfortunately oncology drug prescriptions are not quite so simple! Fortunately it’s not too complicated to understand either, but there is a little math. In this note I explain the different ways cancer drug doses are measured and the ways cancer drugs are given. If you get into the details of examining treatments you will probably be faced with a fair variety of doses and schedules, and you may need to compare doses to make sense of the results and choose among the options.Parlez Vous Metric?If you are from just about anywhere but the US you already use the Metric System. Wherever you are from, the weights and measures used in describing drug doses are metric. If you need a review take a trip to The Metric System SchoolHow an Amount of Drug is MeasuredThe measure of most drugs is simply weight, usually in milligrams, sometimes in micrograms or grams. Some drugs, particularly, biologic preparations are measured in “International Units” or IU. An IU is a standardized measure of biological activity or potency based on a quantitative assay rather than weight and is used when the preparation is not an exact chemical formula or when various related substances have the same type of biological effect. The assay used and the exact definition of an “IU” is completely different for different substances. Normally any pharmaceutical drug will have a standardized number of IU per milligram weight of drug, so it is possible to convert from IU to mg. If there are various preparations of the drug available, IU is a more appropriate measure of how much drug you are getting than milligrams. Sometimes to compare doses from one study in the medical literature to those from another you may have to find out which preparations were used and what the conversion factors are and convert mg to IU. Most of the time the measure is simply weight and this problem does not occur.Dose Adjustment by Body SizeMany cancer drugs are toxic and the range between maximum benefit and severe side effects is narrow. So doses are adjusted for the size of your body. To do this there needs to be a measurement of “the amount of you”. Then a dose can be given as amount of drug per amount of you.How the “Amount of You” is MeasuredThere are two basic ways this is done. The obvious simple way is just to weigh you. The Amount of You is just your weight in Kilograms. In this case the amount of a dose will be given in Milligrams of Drug per Kilogram of body weight abbreviated mg/kg (Or International Units of Drug per Kilogram of body weight, abbreviated IU/kg).Oncologists sometimes use a more complicated way of measuring your body size, your Body Surface Area (BSA). BSA is measured in square meters, abbreviated m2. I believe this is an attempt to compensate for the fact that people, particularly people with cancer, may be underweight or overweight and to try to give them an amount of drug that would be appropriate for what their size should be, disregarding how much fat and muscle they have, which generally doesn’t greatly influence how much drug is needed.So how do oncologists measure BSA? That’s what I wanted to know when I was reading papers and investigating treatments and saw BSA used to standardize doses of Interleukin-2. I figured there must be some sort of highly complex and no doubt uncomfortable apparatus for measuring your surface area, so I asked my doctor, and was shown a chart on her wall. It turns out that they don’t actually measure anyone’s BSA, they estimate it with a rather complicated formula based on your height and weight. If two people weigh the same, the taller one will have a higher estimated BSA. If two people are the same height, the heavier one will have a higher estimated BSA. Want to know your BSA? Check out Dr. Steven Halls’ BSA CalculatorConverting between BSA and Body Weight(Or why you can’t get there from here unless you take the short cut)You might want to convert between BSA and Body Weight to compare doses from two different protocols where one measures one dose in mg/kg/dose and the other in mg/m2. You might want to do this to see if results from two different studies reported in the literature used comparable dosing, unfortunately, there is no fixed conversion factor between BSA and Body Weight because BSA varies with both weight and height. But, it should be possible to come up with an average conversion factor based on the BSA and weight of an “average” person. According to Dr. Steven Halls’ BSA Calculator the 50th percentile of weight for adult males is 80kg and the 50th percentile of height is 175cm and together these measurements give a BSA of 1.97m2. Therefore, for an average male 0.025 mg/kg is about 1 mg/m2 (the result for the average adult female is virtually the same).When I was investigating Interleukin-2 treatments, I decided I wanted to get the highest dose possible because it looked like there was a trend towards better results with higher doses. I was also willing to accept the risk of higher doses. But some of the protocols I investigated defined a dose in mg/kg while others defined it in mg/m2. I wanted to know which would have the highest dose for me. Figuring this out is easy – just use Dr. Steven Halls’ BSA Calculator to calculate your BSA and get the absolute amount of drug per dose and then do the same thing to calculate the amount per dose you would get in the other protocol where dosing is per kilogram body weight and compare the two. As an example suppose in Protocol A, “Cureomycin” is given at 1.33mg/m2/dose and your BSA is 2.0 whereas in protocol B “Cureomycin” is given at 0.033 mg/kg and you weigh 90kg. Then in Protocol A, one dose for you will be 1.33 X 2 = 2.66mg, and in protocol B one dose for you will be 90 X 0.033 = 2.97mg.Dosing Schedules and “Dose Intensity”In comparing various protocols you will find that not only do doses vary from one protocol to the next, but how many doses and when they are given also varies. This can make comparisons difficult or impossible. The concept of “Dose Intensity” may allow a rough comparison. Dose Intensity is the total amount of drug given in a fixed unit of time (usually 1 week). So if Protocol A has 1 dose per day at 1 mg/kg/dose and protocol B has two doses per day at 0.5 mg/kg/dose they both have the same dose intensity, 7 mg/kg/week. According to the standard oncology text, Principles and Practice of Oncology, at least for cytotoxic drugs the main difference in different schedules is the side effects, but the total amount of drug the patient gets mainly determines the effectiveness. This is obviously a broad generalization. The schedule may be critically important if a particular schedule allows a higher, more effective dose (but note that more is not always better – sometimes “more” is more toxic, without being more effective!)Continuous Infusion DosingSo far I have been talking as though doses are always discrete events as in taking a pill or getting a short IV infusion (called a bolus). Sometimes drugs are given by continuous infusion. This can be done outpatient with an implantable pump or in the hospital with the an external programmable IV pump. In this case there is no such thing as amount of drug per “dose” but usually dose is given as an amount per day, for instance in units of mg/kg/day.Route of AdministrationDrugs can be given orally, injected into a vein (given intravenously), or through injections under the skin (subcutaneously). The amount absorbed and how the drug’s concentration varies over time in different parts of the body will depend on how it is given so be aware of this when looking at different protocols which use different routes of administration.