Dosage Calculations

As I mentioned before, I am receiving 5.8 mg of the trial drug MLN9708, which they have calculated as my Maximum Tolerated  Dose (MTD).  It turns out that the MTD is not a fixed value for each patient, but rather is normalized to the patient's Body Surface Area (BSA).  I was curious about two things:  1) why use BSA?; and 2) how is BSA computed?  So I decided to do a little research.

The ensuing discussion is a bit on the technical side (which is my wont).   Some of you may tend to zone out, so I give you technophobes permission to skip the rest of this post.  In fact, you can all skip the rest of this post if you like.

At first blush, one might think that dosage should be proportional to body weight rather than surface area.  However, the objective is to estimate how well the body metabolizes and eliminates the medication.  BSA is a better indicator of metabolic mass than body weight, since it is less affected by abnormal fat (adipose) mass, which just sits there like a lump.

There are numerous formulas in the literature for calculating BSA, but the most prevalent one in use today for clinical purposes is:

BSA (sq m) = SQRT [ weight (kg) x height (cm) / 3600]

This formula was first published by Mosteller in 1987.  It is gaining support as a common standard for chemotherapy medicine doses, mainly because it can be memorized and easily computed with a hand-held calculator.  Note that this formula is not dimensionally correct, so the the 3600 is simply a classic "fudge factor", based on fitting the formula to American height and weight percentile data.

The average BSA value for adult men in the USA is 1.9 sq m.  My BSA computes to be 1.96 sq m.  (I obviously have an excess of that adipose fat stuff.)  The MTD level of the MLN9708 drug has been determined in this Phase 1 clinical trial to be 2.97 mg per sq m of BSA.  Thus, my computed dose level is 1.96 x 2.97 = 5.8 mg.

I don't know about you, but I feel much better having put these burning questions to rest.  I'll try not to be too nerdy in future posts, but sometimes I just can't help myself.