Safety and early efficacy assessment of liposomal daunorubicin (DaunoXome) in adults with refractory or relapsed acute myeloblastic leukaemia: a phase I–II study

• Published in: British journal of haematology Vol. 116; no. 2; pp. 308 - 315
• Main Authors: Fassas, A., Buffels, R., Anagnostopoulos, A., Gacos, E., Vadikolia, C., Haloudis, P., Kaloyannidis, P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.02.2002
• Subjects: acute myeloblastic leukaemia; anthracycline; chemotherapy; efficacy; liposomal daunorubicin
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2002.03292.x

We have conducted a phase I/II trial to determine the maximum tolerated dose, early safety and efficacy of single‐agent liposomal daunorubicin in relapsed or refractory acute myeloid leukaemia (AML). Successive cohorts of six patients received escalated doses of 75, 100, 125 or 150 mg/m2 of DaunoXome for three consecutive days. Responding patients received a further consolidation cycle of DaunoXome at a dose identical to the one inducing complete or partial remission at the various dose levels. Twenty‐eight patients with a median age of 50·5 years were enrolled. A maximum tolerated dose was determined at 150 mg/m2. Twelve patients received the second cycle. DaunoXome was well tolerated at all administered levels; dose‐limiting toxicities included nausea and vomiting, mucositis and two episodes of cardiotoxicity resulting in the death of two patients. The overall response rate was 46% with a median duration of response of 180 d and a median duration of survival of 208 d. Ten patients demonstrated a complete response following cycle 1, and a further four entered partial response with the first cycle (marrow blasts between 5% and 10%). Of these, three attained complete response with the second cycle (total complete response 13/28). Our results indicate that DaunoXome at a dose of 150 mg/m2 displays acceptable toxicity in a 3‐d regimen followed by a 3‐d consolidation course at 100 mg/m2/d. At this dose schedule, interestingly high remission rates were achieved, justifying further evaluation of DaunoXome for the treatment of relapsed or refractory AML patients.