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6584 Background: Patients (pts) with secondary AML (AML following an antecedent hematologic disorder or following known exposure to leukemogenic agents) are often elderly, with comorbid illness, and have a dismal prognosis. Secondary AML responds poorly to standard chemotherapy, with low response rates and short durations of remission. Amonafide (Am) is an ATP independent topoisomerase 2 inhibitor that in prior clinical studies had myelosuppression as the dose-limiting toxicity. Two phase 1 trials evaluated Am as either a single agent or in combination with ara-C in pts with relapsed/refractory or secondary AML. This retrospective review was performed to assess the activity of Am specifically in pts with secondary AML. Methods: In study AM-03, 5 pts with secondary AML were treated with a fixed dose (1000, 1100, or 1400 mg/m 2 /day) of Am IV over 2 hrs daily × 5. In study AM-04, 15 pts with secondary AML were treated with ara-C 200 mg/m 2 /day CIV days 1–7 and a fixed dose (600, 700 or 800 mg/m 2 /d) of Am IV over 2 hrs daily on days 1–5. All clinical trial data were reviewed for assessment of hematological and cytogenetic response. Results: Across the two studies, 10 of 20 (50%) pts responded to Am (9 CR, 1 CRi). In study AM-03 (Am monotherapy), 3 of 5 (60%) pts responded, with median duration of response 7.5 months (range 2.5 - 8). None of these 3 pts received additional post-remission therapy. In study AM-04 (Am + ara-C), 7 of 15 pts (47%) responded, with median duration of response 8 months (range 1 ¾ to >60 months). 4 of these 7 pts received additional post-remission therapy. Cytogenetic analysis prior to and following Am therapy was available for 9 of the 10 pts with secondary AML who responded to Am in the 2 studies. Cytogenetics were abnormal prior to Am therapy in 5 of these 9 pts, 3 (60%) of whom achieved cytogenetic CR. Conclusions: Am shows significant activity in secondary AML, both as monotherapy and in combination with ara-C. A phase 2 trial of Am + ara-C in pts with secondary AML is currently enrolling patients. Table: see text
Allen et al. (Tue,) studied this question.