title: Pharmacologic modulation strategies to reduce dose requirements of anticancer therapy while preserving clinical efficacy.
abstract: Drug interactions may be exploited to overcome pharmacokinetic issues in order to improve the therapeutic index of a drug, with clinical goals of reducing the dose of the active drug while preserving efficacy or reducing toxicity. This strategy has been used in infectious disease and transplant medicine, and, more recently, in oncology. Pharmacologic modulation strategies range from coadministration of either a drug that inhibits a metabolizing enzyme that would inactivate the drug of interest, a drug that induces an enzyme that activates the drug of interest or a drug that inhibits transporters that affect the uptake or elimination of the drug of interest. This review will discuss pharmacologic modulation strategies that have been tested clinically in order to increase systemic drug exposure. Important examples include ketoconazole inhibition of hepatic CYP3A4 in order to increase systemic exposure to docetaxel, irinotecan and etoposide, and cyclosporine inhibition of intestinal ATP-binding cassette transporters in order to decrease the toxicity of irinotecan and increase the bioavailability of oral docetaxel, paclitaxel and topotecan.
authors: Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore.
authors: Ying-Kiat
authors: YK
authors: Zee
authors: Boon-Cher
authors: BC
authors: Goh
authors: Soo-Chin
authors: SC
authors: Lee
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents