The Pharmaceutical Journal
Vol 270 No 7231 p44
11 January 2003

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Journal of the National Cancer Institute abstract (more)

Call to abandon body surface area for dosing anticancer drugs

Body surface area should not be used to determine starting doses of anticancer agents in phase I trials, researchers say. Instead, alternative dosing strategies should be evaluated.

Dr Sharyn Baker, Johns Hopkins University, Baltimore, and colleagues retrospectively assessed the pharmacokinetics of 33 agents tested in phase I trials from 1991 to 2001 as a function of body surface area in 1,650 adults with cancer. Twelve of the drugs were administered orally, 19 intravenously and two by both routes.

Body surface area, the traditional way of determining individualised anticancer drug doses, has previously been thought to reduce interpatient variability to drug exposure and effects. However, the researchers found that, for all but five agents, body surface area-based dosing was not associated with a reduction in interpatient variability in drug clearance. They also found that for the agents for which clearance was associated with body surface area, only up to a third of the total variability could be explained by differences in body surface area.

The researchers recommend that the practice of calculating starting doses based on body surface area in phase I trials should be abandoned. They say that a fixed total dose is feasible for use in such trials for the development of both cytotoxic and non-cytotoxic targeted anticancer agents and should be calculated on the basis of an average body surface area of 1.86m².

They suggest that to produce more rational dosing schemes for oncology practice dose refinement for novel targeted agents should be based on finding an exposure that produces a biologic or molecular effect on a drug target that is associated with a desired therapeutic outcome or avoidance of a toxicologic outcome. "For cytotoxic agents that have a narrow therapeutic window, efforts should continue to focus on defining individual doses that are based on patient characteristics that are known to affect drug clearance (eg, age, sex, renal function and use of concomitant medications)."

The study is published in the Journal of the National Cancer Institute (2002;94:1883).