Comparison of antitumor activity of standard and investigational drugs at equivalent granulocyte-macrophage colony-forming cell inhibitory concentrations in the adhesive tumor cell culture system: an in vitro method of screening new drugs.
We compared the in vitro growth inhibition of primary human tumor cells in the adhesive tumor cell culture system (ATCCS), exposed to the investigational agents caracemide, spirogermanium and taxol and to standard chemotherapy agents at equitoxic concentrations for granulocyte-macrophage colony-forming cells (GM-CFC) in vitro. Clinically active standard agents tested at up to GM-CFC 90% inhibitory concentrations (IC90) resulted in in vitro activity (greater than or equal to 50% tumor growth inhibition) in at least 30% of tumors tested. In vitro responses for taxol, caracemide and spirogermanium were 78%, 9% and 7%, respectively. This paper proposes a model that incorporates two hypotheses: (1) myelotoxic drugs which inhibit tumor growth at concentrations equal to or less than equitoxic GM-CFC ICs will demonstrate clinical activity; and (2) both myelotoxic and particular nonmyelotoxic drugs inactive in vitro at these doses will not be active clinically. If this drug screening concept is valid, taxol may be clinically more active than caracemide and spirogermanium.
D000470:Alkaloids / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D017239:Paclitaxel; D013141:Spiro Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000470:Alkaloids; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009942:Organometallic Compounds; D013141:Spiro Compounds; C026818:spirogermanium; C044466:caracemide; D017239:Paclitaxel; D006918:Hydroxyurea