Piroxantrone is one of a series of compounds commonly known as anthrapyrazoles developed in an effort to combine the broad antitumor activity of the anthracyclines with decreased myocardial toxicity. The mechanism of action of piroxantrone and other anthrapyrazoles is incompletely understood but likely involves DNA binding with induction of DNA strand breaks, DNA-protein cross-linking, and inhibition of DNA, RNA, and protein synthesis. Collectively, these findings suggested an interaction with topoisomerase II. Piroxantrone demonstrated antitumor activity in a wide spectrum of experimental systems against breast carcinoma, colon carcinoma, sarcoma, melanoma and leukemia. Piroxantrone is inactive in patients with persistent, progressive, or recurrent ovarian cancer who recently had received a platinum-based regimen. Piroxantrone has detectable but minimal activity against disseminated malignant melanoma. A phase II clinical trial of the piroxantrone administration for the treatment of advanced metastatic or recurrent endometrial cancer was prematurely terminated due to lack of patient accrual.