Clinical pharmacology of anticancer agents in relation to formulations and administration routes.
In the past years, alternative administration routes and pharmaceutical formulations of anticancer agents have been investigated in order to improve conventional chemotherapy treatment. The impact of these adjustments on the pharmacokinetics and pharmacodynamics is discussed. A review of the literature shows many examples of alternative administration forms of anticancer agents with improved pharmacokinetics. Local administration routes have been investigated in order to reduce the systemic toxicity and to enhance the local efficacy of conventional chemotherapy. Oral administration of anticancer agents is preferred by patients for its convenience and its potential for outpatient treatment. In addition, oral administration facilitates a prolonged exposure to the cytotoxic agent. However, poor bioavailability and substantial interpatient variability are noted as limitations for oral chemotherapy. Increased tumour selectivity can also be achieved by the use of specific pharmaceutical formulations, such as liposomes and macromolecular drug conjugates. The composition of these formulations often determine the pharmacokinetic behaviour of the formulated drug. In conclusion, several alternative administration forms of anticancer agents have been designed in the past years, with the potential for improvement of conventional chemotherapy, however, more extensive clinical evaluation of these novel strategies is warranted to prove their real clinical value.
Department of Medical Oncology, The Netherlands Cancer Institute4 / Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands.
J M
JM
Terwogt
J H
JH
Schellens
W W
WW
Huinink
J H
JH
Beijnen
D000284:Administration, Oral; D000287:Administration, Topical; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic; D004333:Drug Administration Routes; D006801:Humans; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous
D000970:Antineoplastic Agents