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a Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; b Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands; c Division of Drug Toxicology, Faculty of Pharmacy, Utrecht University, Utrecht, The Netherlands; d Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Correspondence: J.H.M. Schellens, M.D., Ph.D., The Netherlands Cancer Institute/Department of Medical Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Telephone: 31-0-20-5122569; Fax: 31-0-20-5122572; e-mail: jhm{at}nki.nl
The oral bioavailability of many cytotoxic drugs is low and/or highly variable. This can be caused by high affinity for drug transporters and activity of metabolic enzymes in the gastrointestinal tract and liver. In this review, we will describe the main involved drug transporters and metabolic enzymes and discuss novel methods to improve oral treatment of affected substrate drugs. Results of preclinical and clinical phase I and II studies will be discussed in which affected substrate drugs, such as paclitaxel, docetaxel, and topotecan, are given orally in combination with an inhibitor of drug transport or drug metabolism. Future randomized studies will, hopefully, confirm that this strategy for oral treatment is at least as equally effective and safe as standard intravenous administration of these drugs.
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