The anthracyclines: will we ever find a better doxorubicin?
The anthracyclines are the class of antitumor drugs with the widest spectrum of activity in human cancers, and only a few cancers (eg, colon cancer) are unresponsive to them. The first two anthracyclines were developed in the 1960s. Doxorubicin (DOX) differs from daunorubicin (DNR) only by a single hydroxyl group. This fact has spurred researchers worldwide to find analogs of DOX that have less acute toxicity, cause less cardiomyopathy, can be administered orally, and/or have different, or greater, antitumor efficacy. Five DOX/DNR analogs are marketed in other countries, and one (idarubicin) is available in the United States. None of these analogs have stronger antitumor efficacy than the original two anthracyclines, but there are some differences in toxicity. Methods have been fashioned to keep the peak plasma level of DOX muted to minimize cardiotoxicity, but the only apparently effective method available so far (prolonged drug infusion) is cumbersome. The bisoxopiperazine class of drugs (especially dexrazoxane) provides protection against anthracycline-induced cardiomyopathy and has much promise for helping mitigate this major obstacle to prolonged use of the anthracyclines. The DOX analogs being evaluated in the 1990s have been selected for their ability to overcome multidrug resistance in cancer cells. Thirty years after discovery of the anticancer activity of the first anthracycline, some means of reducing anthracycline toxicity have been devised. Current studies are evaluating increased doses of epirubicin to improve anthracycline cytotoxicity, while limiting cardiotoxicity, but at present DOX still reigns in this drug class as the one having the most proven cancerocidal effect.
Weiss
R B
RB
Department of Medicine, Walter Reed Army Medical Center, Washington, DC 20307.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004341:Drug Evaluation; D015507:Drugs, Investigational / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy
D000903:Antibiotics, Antineoplastic; D015507:Drugs, Investigational; D004317:Doxorubicin; D003630:Daunorubicin