IN-VITRO CONCENTRATION RESPONSE STUDIES AND IN-VITRO PHASE-II TESTS AS THE EXPERIMENTAL BASIS FOR REGIONAL CHEMOTHERAPEUTIC PROTOCOLS

The theoretical pharmacologic benefit of regional vs. systemic chemoth erapy is defined and the concentration response behavior of cytostatic drugs and their optimal exposure times are described with human cance r cell lines (HT29, NMG64/84) and fresh human tumor cell suspensions i n the human tumor colony assay (HTCA). The theoretical pharmacological advantages are 5.8 to 6 for adriamycin (ADM), 8 for cisplatinum (CDDP ), 6.3 for epidoxorubicin (EPI), 22 to 58 for 5-fluorouracil (5FU), 4. 6 for mitomycin C (MMC), and 6.3 for mitoxantrone (NOV). The drugs dif fered in their cytotoxic potency in vitro and thus also potential effi cacy for regional chemotherapy; however, all but 5-fluorodeoxyuridine (5FUDR) exerted cytotoxicity dependent on exposure time and concentrat ion. On average, elevation of the test concentrations by 1 lg doubled responses in fresh human tumor cell suspensions. From these results an d clinical considerations, optimal times were defined for the regional chemotherapy strategies of hepatic artery infusion, intraperitoneal i nstillation, and chemoembolisation as performed at our institution. (C ) 1998 Wiley-Liss, Inc.