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  • anthracyclines  (1)
  • clinical trials  (1)
  • Springer  (2)
  • 1995-1999  (2)
  • 1985-1989
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  • Springer  (2)
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  • 1995-1999  (2)
  • 1985-1989
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  • 1
    ISSN: 1573-0646
    Keywords: anthracyclines ; cloning assay ; morpholino anthracyclines ; MX2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 μg/ml either for 1 hour (201 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19%in vitro response at 0.05 μg/ml and 69% at 0.5 μg/ml) than with 1-hour exposure (1.3% at 0.05 μg/ml and 12% at 0.5 μg/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 μg/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity in patients with those tumors.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 14 (1996), S. 265-270 
    ISSN: 1573-0646
    Keywords: gemcitabine ; clinical trials ; human tumor cloning assay (HTCA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 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 μg/ml than at 2.0 μg/ml. Based on subsequent clinical phase II data, the HTCA correctly predicted the wide spectrum of the clinical activity of gemcitabine.
    Type of Medium: Electronic Resource
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