Phase I clinical evaluation of diaziquone in childhood cancer.
Diaziquone (AZQ), a new lipid-soluble antitumor agent, was given by 15-30-minute infusion on a daily X 5 schedule to 47 children with refractory solid tumors and leukemia. The starting daily dose of 6 mg/m2 was escalated to 10 and 35 mg/m2 in patients with solid tumors and leukemia, respectively. In patients with solid tumors, myelosuppression was dose-limiting at a daily dose of 10 mg/m2. In patients with leukemia, prolonged pancytopenia and bone marrow hypoplasia were observed at daily doses greater than or equal to 25 mg/m2. At these higher doses, significant hyperbilirubinemia associated with sepsis was also seen. Corresponding increases of transaminases or alkaline phosphatase and significant hemolysis were not noted. The maximum tolerated dose for this daily dose schedule was 9 mg/m2 in children with solid tumors and 25 mg/m2 in children with relapsed leukemia. Responses to AZQ included stabilization of disease in osteosarcoma, neurofibrosarcoma, pinealoma, and ependymoma. A patient with juvenile chronic myelocytic leukemia in blast crisis converted back to the chronic phase. A patient with acute lymphoblastic leukemia had a substantial decrease in cerebrospinal fluid blast count. Bone marrow aplasia was achieved in children with acute lymphoblastic leukemia and acute nonlymphoblastic leukemia; however, remissions were not achieved. A phase II study of AZQ in children with refractory malignancies is now being performed by the Childrens Cancer Study Group.
D000293:Adolescent; D000367:Age Factors; D001388:Aziridines / Q000009:adverse effects / Q000627:therapeutic use*; D001389:Azirines / Q000627:therapeutic use*; D016227:Benzoquinones; D001853:Bone Marrow / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D007945:Leukemia, Lymphoid / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D010976:Platelet Count
D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; D006454:Hemoglobins; C029108:diaziquone