In vivo antitumor activity of F 11782, a non‐intercalating dual catalytic inhibitor of topoisomerases I and II, against a panel of human tumor xenografts

The marked in vivo antitumor activity of F 11782 against murine experimental tumors (Kruczynski et al., Br J Cancer 83: 1516–24, 2000) has now been confirmed in a panel of human tumor xenografts. Using an intermittent schedule of six administrations over 2 weeks, F 11782 showed major activity in four of eight xenograft models. Excellent activity was noted versus the CAKI-1 (renal) model, with regressions at the two highest doses, and marked activity against DLD-1 (colon) xenografts, also resulting in regressions at the MTD. Marked antitumor activity was also observed against DU 145 (prostate) and GLC4 (small-cell lung) tumors. At optimal doses, significant T/C values ranged from 3 to 29%, with significant growth delays of 1.5–5.6, without major body weight loss. This tumor growth inhibition induced by F 11782 was sustained with time for ≥6 weeks post implant. In contrast, no real activity was recorded against NCI-H460 (non small-cell lung) tumors and only minor responses, with optimal T/C values of <42%, noted in the rapidly proliferating SF-295 (CNS) and LOX IMVI (melanoma) xenografts or the chemo-refractory LoVo (colon) model. Overall, this study showing a 50% response rate with definite antitumor activity across a broad spectrum, coupled with its unique mechanistic profile, has prompted the further development of F 11782.