Activity of gemcitabine in a human tumor cloning assay as a basis for clinical trials with gemcitabine. San Antonio Drug Development Team.
2',2'-difluorodeoxycytidine (LY 188011, Gemcitabine, Gemzar) has recently been approved both in Europe for the treatment of patients with non-small cell lung cancer and in the United States for patients with pancreatic cancer. Since the initial discovery of the compound, we have been evaluating the in vitro activity of gemcitabine against human tumor colony-forming units taken directly from patients and growing in soft agar (in the human tumor cloning assay-HTCA). A total of 315 specimens have had gemcitabine tested against them with 44% giving evaluable results. Gemcitabine has been found to be active against colony-forming units from patients with non-small cell lung, breast, ovarian, and pancreatic cancers. A concentration-dependent in vitro response was noted with a higher in vitro response rate noted at 20 micrograms/ml than at 2.0 micrograms/ml. Based on subsequent clinical phase II data, the HTCA correctly predicted the wide spectrum of the clinical activity of gemcitabine.
Von Hoff
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Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX, USA.
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D017321:Clinical Trials, Phase I as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy; D014410:Tumor Stem Cell Assay; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine