Clinical studies with new anthracyclines: epirubicin, idarubicin, esorubicin.
Analogue development is one of the most intensively pursued anticancer drugs research projects. The rationale in anthracycline analogue development followed by Farmitalia Carlo Erba has been the selection of agents with improved therapeutic index with respect to the parent structures, different spectrum of activity, reduced toxicity to the myocardium and oral route of administration. The clinical development is based on Phase I, II and III studies. However, the best definition in terms of activity and toxicity of an anticancer agent is accomplished with Phase II clinical trials, especially if they are comparative in a randomized fashion with the parent compound. Esorubicin has just started Phase II clinical testing. Phase I studies have shown hints of activity in several malignant diseases. Idarubicin has already been shown to be an important antileukaemic agent in Phase II-III studies. Moreover this compound is the first oral anthracycline that has shown activity in breast cancer, lymphomas and leukaemias, together with potential for reduced cardiac toxicity. Epirubicin, which is now in Phase III clinical development, has been shown to possess a better therapeutic index than doxorubicin since it induces less acute toxicities (nausea and vomiting, mucositis, myelosuppression) and less cardiotoxicity than its parent compound, without loss of activity in responsive tumours.
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D002986:Clinical Trials as Topic; D003630:Daunorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004341:Drug Evaluation; D015251:Epirubicin; D006321:Heart / Q000187:drug effects; D006801:Humans; D015255:Idarubicin; D009369:Neoplasms / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D004317:Doxorubicin; C030851:esorubicin; D015255:Idarubicin; D003630:Daunorubicin