Pharmacokinetic optimisation of anticancer therapy. 1991

J Liliemark, and C Peterson
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.

It is obvious that there are great problems with pharmacokinetic individualization of anticancer therapy. The strong relationship between dose intensity (total dose/unit time) and response revealed in clinical trials with some tumours provides a strong support for studies seeking relationships between the individual plasma pharmacokinetic profile and response to treatment. Unfortunately, studies that define a therapeutic window are sparse, and trials that prospectively test such models are even rarer. Thus, for most cancer drugs, it is not possible to give any definite advice on how to use pharmacokinetic determinations to establish individualised therapy, and there is therefore a definite need for such studies. It is important, however, that attempts to establish relationships between drug concentrations and therapeutic effects be founded on a sound theoretical base. When drugs, mainly antimetabolites, are extensively metabolised intracellularly and interact with intracellular processes about which there are data showing a strong interindividual heterogeneity, such data must be considered when designing pharmacokinetic investigations. Cytarabine and fluorouracil are good examples of this. The monitoring of intracellular drug/metabolite concentrations or of the direct biochemical events in the tumour cells seems to be a promising approach with such drugs. It also needs to be emphasised that pharmacokinetically guided individualization cannot be achieved before a therapeutic window is established, i.e. a knowledge of the relationship between drug concentration and clinical effects. The investigators in this field accept a great responsibility when clinical studies are undertaken: a poorly designed study showing no benefit from pharmacokinetically guided individualization can impair the possibilities of performing more adequate studies in the future.

UI MeSH Term Description Entries
D007674 Kidney Diseases Pathological processes of the KIDNEY or its component tissues. Disease, Kidney,Diseases, Kidney,Kidney Disease
D008107 Liver Diseases Pathological processes of the LIVER. Liver Dysfunction,Disease, Liver,Diseases, Liver,Dysfunction, Liver,Dysfunctions, Liver,Liver Disease,Liver Dysfunctions
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D014481 United States A country in NORTH AMERICA between CANADA and MEXICO.
D016903 Drug Monitoring The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. Monitoring, Drug,Therapeutic Drug Monitoring,Drug Monitoring, Therapeutic,Monitoring, Therapeutic Drug
D049673 History, 20th Century Time period from 1901 through 2000 of the common era. 20th Century History,20th Cent. History (Medicine),20th Cent. History of Medicine,20th Cent. Medicine,Historical Events, 20th Century,History of Medicine, 20th Cent.,History, Twentieth Century,Medical History, 20th Cent.,Medicine, 20th Cent.,20th Cent. Histories (Medicine),20th Century Histories,Cent. Histories, 20th (Medicine),Cent. History, 20th (Medicine),Century Histories, 20th,Century Histories, Twentieth,Century History, 20th,Century History, Twentieth,Histories, 20th Cent. (Medicine),Histories, 20th Century,Histories, Twentieth Century,History, 20th Cent. (Medicine),Twentieth Century Histories,Twentieth Century History

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