Inpharma 1246 - 15 Jul 2000

Exatecan: potent in vitroantitumour activity

The camptothecin derivative exatecan* [DX-8951f]exhibits potent cytotoxicity against various drug-resistant cancer cell lines, report researchers from Japan.

They compared the cytotoxic effects of exatecan withthose of various anticancer agents (e.g. paclitaxel,doxorubicin [adriamycin] and fluorouracil) against 8drug-resistant cell lines derived from the human oat celllung cancer cell line PC-6.

Drug-resistant cell line PC-6/VP1-1, established byexposure to etoposide, showed cross-resistance topaclitaxel, doxorubicin, vincristine and etoposide, aswell as to the irinotecan metabolite SN-38,camptothecin-11 and topotecan. However, this cell linewas sensitive to the camptothecin derivative9-aminocamptothecin (9-AC), camptothecin andexatecan.

Drug-resistant cell lines PC-6/SN2-5, established byexposure to SN-38, and PC-6/CPT2-2, established byexposure to camptothecin-11, were highly resistant tomost of the camptothecin derivatives (e.g. SN-38,topotecan and 9-AC) but showed relatively weakresistance to exatecan and camptothecin.

The researchers conclude that exatecan may ‘showantitumor effects even on tumors refractory to otheragents’.* Daiichi; phase II

Ishii M, et al. Growth inhibitory effect of a new camptothecin analog, DX-8951f,on various drug-resistant sublines including BCRP-mediated camptothecinderivative-resistant variants derived from the human lung cancer cell line PC-6.Anti-Cancer Drugs 11: 353-362, Jun 2000 800833523

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Inpharma 15 Jul 2000 No. 12461173-8324/10/1246-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved