title: 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.
abstract: 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 > or = 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.
authors.affiliation: Division de Cancerologie Experimentale, Centre de Recherche Pierre Fabre, Castres, France.
authors.forename: A
authors.initials: A
authors.lastname: Kruczynski
authors.forename: C
authors.initials: C
authors.lastname: Ricome
authors.forename: W R
authors.initials: WR
authors.lastname: Waud
authors.forename: B T
authors.initials: BT
authors.lastname: Hill
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009281:Naphthalenes; D011714:Pyrans; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C405744:tafluposide