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 Blackwell 01.02.2002; Blackwell Publishing Ltd
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Daunorubicin - administration & dosage; Daunorubicin - adverse effects; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Hematology; Humans; Leukemia, Myeloid, Acute - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Liposomes; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Recurrence; Remission Induction; Human; Antineoplastic agent; Relapse; Shape; Maximal dose; Acute; Treatment efficiency; Liposome; Malignant hemopathy; Refractory; Antibiotic; Chemotherapy; Daunorubicin; Treatment; Phase II trial; Phase I trial; Adult; Anthracyclins; Acute myelocytic leukemia
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.0007-1048.2001.03292.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.