title: Effective remission induction of refractory childhood acute nonlymphocytic leukemia by VP-16-213 plus azacitidine.
abstract: Thirty-eight children and young adults with advanced acute nonlymphocytic leukemia (ANLL) in relapse were treated with VP-16-213 plus azacitidine (5AZ). Each patient had previously received many chemotherapeutic drugs, including anthracyclines and cytarabine. Initially, 16 patients received a 5-day course of VP-16-213 (100 mg/m(2)) daily x 3 days and 5AZ 9150 mg/m(2)) daily x 2 days, repeated after 9-16 days. Since this treatment produced marrow hypoplasia and complete remission (CR) in only one of 16 patients, a more intensive regimen was devised: the remaining 22 patients received a course of VP-16-213 (200 mg/m(2)) daily x 3 days, followed by 5AZ (300 mg/Fm(2)) daily x 2 days, repeated after 1-2 days until the bone marrow became hypoplastic. After two to four courses, 18 patients had marrow hypoplasia and ten of these achieved CR. The proportion of patients achieving CR with the higher doses was significantly greater than that with the initial doses )P less than or equal to 0.05). The toxicity also increased with the higher doses, with major problems due to prolonged pancytopenia. Supportive therapy was required for severe bleeding and infections. We conclude that the intensive treatment with VP-16-213 plus 5AZ can effectively induce remission in patients with refractory advanced acute nonlymphocytic leukemia.
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001374:Azacitidine / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D010198:Pancytopenia / Q000139:chemically induced; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D011379:Prognosis; D012008:Recurrence
chemical_list: D005047:Etoposide; D011034:Podophyllotoxin; D001374:Azacitidine