Preclinical antitumour activity of F 11782, a novel dual catalytic inhibitor of topoisomerases

F 11782 is a novel inhibitor of topoisomerases I and II, with an original m echanism of action (Perrin et al, 2000), This study, aimed to define its an ticancer efficacy against a series of murine and human tumour models, has p rovided evidence of major antitumour activity for F 11782. This was demonst rated as a high level of activity against the P388 leukaemia, as reflected by increased survival of 143-457%, when administered i.p., p.o. or i.v. as single or multiple doses, and proved consistently superior to etoposide or camptothecin tested concurrently. Single or multiple i.p. doses of F 11782 also proved highly active against the s.c. grafted B16 melanoma, significan tly increasing survival (P < 0.001) and inhibiting tumour growth (TIC of 0. 3%), again superior to etoposide tested concurrently, Furthermore, F 11782 inhibited the number of pulmonary metastatic foci of the B16F10 melanoma by 99%. In human tumour xenograft studies, multiple i.p. doses of F 11782 res ulted in major inhibitory activity against MX-1 (breast) tumours (T/C of 0. 1%), as well as causing definite tumour regressions, whereas none resulted from similar experimental treatments with etoposide, Significant activity w as also recorded with F 11782 against the relatively refractory LX-1 (lung) xenografts, with an optimal T/C value of 19%. it was notable that the anti tumour activity of F 11782 was consistently demonstrated over a wide range of 2-6 dose levels, providing evidence of its good overall tolerance. In co nclusion, these results emphasize the preclinical interest of this novel mo lecule and support its further preclinical development. (C) 2000 cancer Res earch campaign http://www.bjcancer.com.