gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Dosing of anticancer drugs: flat dose vs. body-surface-area normalized dose

Meeting Abstract

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27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocIS076

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Veröffentlicht: 20. März 2006

© 2006 Mross.
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Mg/m² dosing of antitumor drugs has become accepted since 40 years without questioning the soundness or the validity of the underlying assumptions. This practice is a legacy of species scale-up and the attempt to initiate clinical studies with rational doses on the basis of animal toxicity data. One can either use the body weight (BW) or the body-surface-area (BSA) for normalization the drug dose. Both parameters have to be measured (BW) and calculated (BSA). The first question is: how precise are body weight measurements and how precise are calculations of the BSA by formulas developed decades ago with only a few persons. It is more approbriate to use the term that BW and BSA are estimates with some errors but no one can calculate how large the error really is. The second question is: can the pharmacist really prepare exactly dosages on a prescription when eg 87,7 mg of drug X and 1547 mg of drug Y should be prepared? The third question is: will the patient receive every mg of the prescribed dose or is there something left in the infusion bag and lines? Most of the cytotoxic drugs have to be metabolized to become an active drug (eg cylophosphamide, irinotecan) or are metabolized for excretion via liver, bile or kidney. All metabolizing pathways are dependent from enzyme activities eg the cytochrome P-450 system, the glucuronidation and others. It has never been shown that enzyme activities are correlated to BW and/or BSA.

Nearly all of the new developed drugs for anticancer treatment like tyrosine kinase inhibitors are used with a flat dose. Pharmacokinetic studies with many anticancer drugs like platinum compounds, irinotecan, anthracyclines and others have shown, that is not possible to lower the variation of the drug clearence between different sized persons by normalization procedures using BW and BSA. If it is not possible to reach nearly the same drug exposure in each patient by such normalization procedures it would be a rational decision to stop completely this common procedure with BSA-normalized dosing calculations. Flat dose (one dose for all) will minimize dosing errors, will avoid difficult and expensive and time consuming preparing procedures in the pharmacy. Starting with a flat dose do allow, if necessary, a dose titration eg in case of no toxitiy increasing the dose and in case of too much toxicity a decrease of the dose. But for most of all patients in the palliative situation a simple flat dose systems for nearly all used anticancer agents would be possible. The major hurdle is: old habits die hard but we should work on the funeral of the BSA-normalization procedure.