Comparison of DX-8951f and topotecan effects on tumor colony formation from freshly explanted adult and pediatric human tumor cells

Richard A. Lawrence, Elzbieta Izbicka, Robert L. De Jager, Akiko Tohgo, Gary M. Clark, Steven D. Weitman, Eric K. Rowlnsky, Daniel D. Von Hoff

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

DX-8951f, which shows great therapeutic potential, was tested in the human tumor cloning system in adult and pediatric tumor types against which topotecan has been active. In 47 tumors from adults, DX-8951f had definite cytotoxic activity in a concentration-dependent manner with both 1 h and continuous exposures. Topotecan was minimally effective using a 1 h exposure and showed concentration-dependent inhibition with continuous exposure. In head-to-head comparisons at 1 h exposure against adult tumors, DX-8951f was significantly more effective at 0.1 and 1.0 μg/ml than topotecan. In head-to-head comparisons (continuous exposure), 1.0 μg/ml DX-8951f was more effective than topotecan at 1.0 μg/ml in adult tumors, including three of four head and neck, one of two kidney, two of five liver, six of 10 non-small cell lung, five of eight ovarian, four of eight prostate tumors, and in single specimens of breast, mesothelioma, colon and small cell lung tumors. With continuous exposure, DX-8951f and topotecan were equally effective at equimolar concentrations. The maximum tolerated dose for DX-8951f is 3 times that of topotecan, so higher doses of DX-8951f could be administered to patients. DX-8951f is a promising new antineoplastic agent with significant activity against tumors taken directly from patients.

Original languageEnglish (US)
Pages (from-to)655-661
Number of pages7
JournalAnti-cancer drugs
Volume10
Issue number7
DOIs
StatePublished - 1999

Keywords

  • Camptothecin
  • DX-8951f
  • Human tumor cloning
  • Topoisomerase I inhibitors
  • Topotecan

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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