Diaziquone and 2,2'-anhydro-arabinosyl-5-fluorocytosine for the treatment of children with relapsed or refractory acute nonlymphoblastic leukemia.
The authors treated 30 patients ages 1 to 19 with relapsed or refractory acute non-lymphoblastic leukemia (ANLL) with the combination of diaziquone (AZQ) and 2,2'-anhydro-arabinosyl-5-fluorocytosine (AAFC) intravenously in two dose schedules. The first 12 patients were treated with 19 courses of AZQ 30 mg/m2 X 3 days and AAFC 600 mg/m2/dose every 12 hours X 10 doses. An additional patient was treated with three courses at 80% of the above doses. Hepatic toxicity was National Cancer Institute Grade III in eight of 22 and Grade IV in one of 22 courses. Infectious complications were severe in all patients, including responders. One patient achieved a complete remission and one a partial remission; the latter died with marrow aplasia after a second course. Altogether three patients developed profound aplasia and died before marrow recovery. The authors treated a second group of 17 patients with AZQ 22.5 mg/m2/day X 3 days and AAFC 450 mg/m2/dose every 12 hours X 10 doses. Three patients achieved a complete remission and one patient a partial remission for 3, 4, 9, and 9 months, respectively. The remainder had progressive disease or no response. All patients developed profound myelosuppression but no toxic deaths occurred. Hepatic toxicity was reduced. Therapy induced cytoreduction of bone marrow was determined by flow cytometry in ten patients; none of these patients responded during the interval studied. Although AZQ and AAFC are active in childhood ANLL with acceptable toxicity, the combination does not appear more active than AZQ used alone. Future studies should define the role of AZQ in combination with other agents.
Meyers
P A
PA
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Tan
C T
CT
Steinherz
P G
PG
Redner
A
A
D000293:Adolescent; D003504:Ancitabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001388:Aziridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016227:Benzoquinones; D001853:Bone Marrow / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male
D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones; D003561:Cytarabine; C011168:5-fluoro-2,2'-cyclocytidine; D003504:Ancitabine; C029108:diaziquone