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July 22, 1983

Defusing adverse effects of anticancer drugs

JAMA. 1983;250(4):459. doi:10.1001/jama.1983.03340040011008

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Doxorubicin hydrochloride and daunorubicin hydrochloride, two of the most potent drugs in the anticancer arsenal, share, in addition to bone marrow suppression, another serious—sometimes fatal—adverse effect: cardiotoxicity. Recently, however, research at several institutions has begun to yield ways to eliminate this drawback and, in some cases, increase the drugs' potencies in the process.

Researchers at SRI International, Menlo Park, Calif, and Adria Laboratories, Inc, Dublin, Ohio, have developed a doxorubicin derivative that appears to be orders of magnitude more potent than the parent molecule yet free of its main side effect. The newly synthesized molecule, 3′-deamino-3′-(3-cyano-4-morpholinyl) doxorubicin, called "A-489," has been tested against two forms of leukemia and a solid tumor in mice, as well as in DNA/RNA synthesis inhibition trials in cultured tumor cells. The studies indicate that the optimum dose of A-489 is 600 times lower than that of doxorubicin. Results are the same whether the substance is