[Anticancer drug dosing--pharmacogenomic biomarkers or body surface area?].
BACKGROUND
Chemotherapeutic treatment regimes are established for most cancer forms. In general, these substances have extremely narrow therapeutic windows, which render cancer patients vulnerable to over- and underdosing. Individual drug dosing is currently based on the patients' body surface area. This practice is an extrapolation from animal studies. Recent advances in molecular medicine raise the question of whether the present dosing strategy should be adjusted to individual functional DNA variants affecting the metabolism, transport and efficacy of anticancer drugs.


METHODS
This review is based on selected references retrieved from PubMed and the authors' experience in drug treatment of cancer patients.


RESULTS
Several single nucleotide polymorphisms and other DNA variants that contribute to varying clinical response to chemotherapeutic agents were identified. For some drugs it has been shown that unfavourable DNA variants can lead to life-threatening side effects and/or suboptimal treatment.


CONCLUSIONS
There is a compelling need for prospective, randomized studies to establish the prognostic values of pharmacogenomic markers. With few exceptions the current knowledge is insufficient to include genotype analyses in routine planning of anticancer drug treatment. In most clinical situations, individual drug dosing according to body surface area in addition to therapeutic drug monitoring and close clinical surveillance is still the preferred approach to treat cancer patients.
Lehne
Gustav
G
Fagområde medikamentell behandling, Rikshospitalet-Radiumhospitalet, 0310 Oslo. gustav.lehne@medisin.uio.no
Bjørheim
Jens
J
Saeter
Gunnar
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001830:Body Surface Area; D004273:DNA, Neoplasm / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm