Rationale and strategy for prevention of anthracycline cardiotoxicity with the bisdioxopiperazine, ICRF-187.
Anthracyclines are amongst the most effective antitumor agents currently utilized. The major impediment to their use has been the development of cardiotoxicity with chronic administration. In an effort to overcome this limitation we have utilizated an approach to abrogate the cardiotoxicity with a drug, ICRF-187, which protects against the anthracycline cardiomyopathy in all animal species so far tested. This strategy assumes that separate mechanisms of cardiac toxicity and antitumor activity exist. We are currently testing this hypothesis in a randomized clinical trial of women with advanced breast cancer who are randomized to receive 5FU, doxorubicin, and cyclophosphamide (FAC) or FAC plus ICRF-187.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects*; D006801:Humans; D010879:Piperazines / Q000627:therapeutic use*; D011929:Razoxane / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D010879:Piperazines; D011929:Razoxane; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil