Successful local regional therapy with topotecan of intraperitoneally growing human ovarian carcinoma xenografts

Abstract

The therapeutic effects of intraperitoneal topotecan, a water-soluble camptothecin analogue, were investigated in two models of human ovarian carcinoma xenografted intraperitoneally into nude mice: the IGROV-1 tumour, which originated from an untreated patient, and the A2780 tumour, selected for resistance in vitro to cisplatin (A2780DDP). In IGROV-1 tumour-bearing mice, the optimal dose (10 mg kg-1) of topotecan, given intraperitioneally every 4 days for four occasions markedly increased survival time over control mice (300 T/C%) and cured 4/9 mice, and such effects were not achieved by any of the clinically available drugs tested, i.e. cisplatin carboplatin and doxorubicin delivered intraperitonally according to their optimal doses and schedules. In the treatment of A2780DDP tumour-bearing mice, topotecan was very effective since, at dose levels of 6.6 and 10 mg kg-1 every 4 days for four occasions, 15/18 mice survived more than 100 days, and most of them (12/15) were found to be tumour free. The high responsiveness of this tumour to topotecan might be related to the elevated expression of the target enzyme topoisomerase I. From these results, intraperitoneal treatment with topotecan appears to be a promising approach in the therapy of refractory ovarian cancer confined to the peritoneal cavity.