Effective reinduction therapy for childhood acute nonlymphoid leukemia using simultaneous continuous infusions of teniposide and amsacrine.
The combination of teniposide (VM-26) and amsacrine (AMSA) was evaluated in a dose-finding and efficacy study in 58 patients with relapsed or refractory acute leukemia. Both agents were given as simultaneous continuous infusions for 72 h through separate i.v. lines. All patients were evaluable for toxicity and 57 were evaluable for response; only 2 of 20 with acute lymphoblastic leukemia (ALL), acute mixed-lineage leukemia, or chronic myelogenous leukemia in blast crisis achieved a complete remission (CR). More encouraging was a second-remission rate of 43% (13 complete and 3 partial) in the 37 patients with acute nonlymphoid leukemia (ANLL). Responses occurred only in patients who received VM-26 doses of greater than or equal to 200 mg/m2 per day and AMSA doses of greater than or equal to 100 mg/m2 per day. Thus, the CR rate for relapsed ANLL patients who received the higher doses of both agents was 40% (13 of 33). All responders had previously received epipodophyllotoxin therapy and 40% had also received AMSA. All but one patient had severe leukopenia (less than 2.0 x 10(9) leukocytes/l) and thrombocytopenia (less than 50.0 x 10(9) platelets/l) as a results of therapy. Severe mucositis (grade 3 or 4) was the dose-limiting toxicity. Our results indicate that VM-26 plus AMSA, given by continuous infusion, is effective in the treatment of ANLL. Further phase II studies should consider using VM-26 at 200 mg/m2 per day and AMSA at 100 mg/m2 per day, but the best administration schedule remains unclear.
Mirro
J
J
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38101.
Kalwinsky
D K
DK
Grier
H E
HE
Santana
V M
VM
Mason
C
C
Murphy
S B
SB
Dahl
G V
GV
D000293:Adolescent; D000328:Adult; D000677:Amsacrine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001752:Blast Crisis / Q000188:drug therapy / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D009061:Mouth Mucosa; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D012074:Remission Induction; D013280:Stomatitis / Q000139:chemically induced; D013713:Teniposide / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced
D000677:Amsacrine; D013713:Teniposide