Differential activity of topotecan, irinotecan and SN-38 in fresh human tumour cells but not in cell lines

The topoisomerase I inhibitors topotecan irinotecan (CPT-11) and its metabo lite SN-38 were studied in a panel of cell lines and in primary tumour cell s from patients, using a non-clonogenic cytotoxicity assay. All three subst ances showed similar activity patterns in the panel of cell lines establish ed to classify the drugs mechanistically. In the patient tumour cells the d rugs had different exists. In haematological and ovarian cancer samples, SN -38 was much more potent than topotecan, followed by irinotecan, while in c olorectal cancel samples only irinotecan showed substantial activity. This in vitro activity pattern seems to agree with clinical experiences to dare. The inactivity of SN-38 in colorectal cancer suggests irinotecan may also have some other role in addition to being a prodrug to SN-38. This study ra ises questions as to the role and relevance of early preclinical model syst ems in anticancer drug development. and suggests that important information can be obtained from studies using primary cultures of human tumour cells. (C) 2000 Elsevier Science Ltd. All rights reserved.