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Anthracyclines in the treatment of gynecologic malignancies.

OBJECTIVE
The purpose of this article is to present a summary of the pharmacology of anthracyclines as well as to review the results of clinical trials including patients with gynecologic malignancies treated with anthracycline-based therapy.


METHODS
We performed a MEDLINE literature search of relevant clinical trials for the scope of this review that evaluated anthracycline-based therapy in gynecologic malignancies.


RESULTS
Doxorubicin has established activity in carcinomas that arise in the ovary, uterine cervix, and endometrium as well as in uterine sarcomas. However, doxorubicin has structural characteristics that limit its efficacy and safety. Newer anthracyclines with distinct structure, pharmacokinetics, pharmacodynamics, and toxicity profiles have been developed to overcome the limitations of doxorubicin and to further exploit the activity of anthracyclines. Epirubicin is characterized by a structural formula that confers similar cytotoxic antitumor activity with fewer associated side effects than its analogue. Most recently, pegylated liposomal formulations, with distinct pharmacokinetic properties and a favorable toxicity profile, have shown antitumor activity as salvage therapy in ovarian cancer. Intraperitoneal mitoxantrone is also associated with activity in ovarian cancer; however, its clinical use is limited by the severity of local adverse effects.


CONCLUSIONS
The role of anthracyclines in the management of advanced gynecologic malignancies is important as part of first-line therapy or as a salvage approach. Newer anthracycline agents such as epirubicin and pegylated liposomal doxorubicin are associated with a more favorable toxicity profile. Clinical trials are under way to further explore the role of newer anthracycline-based regimens as first-line or salvage treatment in gynecologic malignancies.