USE OF A HUMAN-TUMOR CLONING SYSTEM TO EVALUATE ANALOGS OF METHOTREXATE AND MITOXANTRONE

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 68  (5) , 733-738
Abstract
A human tumor cloning system was used to compare the antitumor activity of trimetrexate (TMQ), a new dihydrofolate reductase inhibitor, and ametantrone, a new anthracenedione, with that of analogs already in clinical trial(methotrexate and mitoxantrone). Sixty-nine of 136 tumors plated for the TMQ study and 84 of 228 tumors plated for the ametantrone study were evaluated for drug-sensitivity assays. The overall in vitro response rates (defined as a .ltoreq. 50% survival of tumor colony-forming units) for TMQ were 20 and 23% at 0.1 and 1 .mu.g/ml, respectively; for ametantrone they were 13, 21, and 26% at 0.1, 1, and 10 .mu.g/ml, respectively. The overall in vitro activity for both new compounds was similar to that of their clinically used analogs, but TMQ was active in 8 of 47 methotrexate-resistant specimens and ametantrone in 9 of 62 mitoxantrone-resistant specimens. A comparison of these in vitro results with the results of phase II clinical trials with both drugs should allow an evaluation of the utility of the human tumor cloning system for predicting clinical antitumor activity of analogs of currently available antineoplastic agents.