Effective reinduction therapy for childhood acute nonlymphoid leukemia using simultaneous continuous infusions of teniposide and amsacrine

• Published in: Cancer chemotherapy and pharmacology 1989-01, Vol.24 (2), p.123-127
• Main Authors: MIRRO, J. JR, KALWINSKY, D. K, GRIER, H. E, SANTANA, V. M, MASON, C, MURPHY, S. B, DAHL, G. V
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Amsacrine - administration & dosage; Amsacrine - adverse effects; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Blast Crisis - drug therapy; Blast Crisis - pathology; Chemotherapy; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Infusions, Intravenous - methods; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemia, Myeloid, Acute - drug therapy; Leukopenia - chemically induced; Male; Medical sciences; Mouth Mucosa; Pharmacology. Drug treatments; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Remission Induction; Stomatitis - chemically induced; Teniposide - administration & dosage; Teniposide - adverse effects; Thrombocytopenia - chemically induced
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/BF00263133

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.