Miser J S, Smithson W A, Krivit W, Hughes C H, Davis D, Krailo M D, Hammond G D
Department of Pediatrics, Mayo Clinic Foundation, Rochester, Minnesota.
Am J Clin Oncol. 1992 Apr;15(2):135-40. doi: 10.1097/00000421-199204000-00008.
We treated 31 children with acute lymphoblastic leukemia (ALL), 14 children with acute nonlymphoblastic leukemia (ANLL) in relapse, and 1 child with chronic myelogenous leukemia (CML) in blast crisis (CALLA negative) with indicine N-oxide in a Phase II study. The efficacy and toxicity of the drug were assessed at two dose levels: 2,000 mg/m2/day for 5 consecutive days (14 patients) and 2,500 mg/m2/day for 5 consecutive days (17 patients). One patient with ALL at each dose level achieved a complete response (CR) lasting 6 months and 1 month, respectively. The patient with CML achieved a partial response lasting 4 months. None of the patients with ANLL achieved a CR. Hepatotoxicity was mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of mild (grade 1 or 2) in 63% and moderate (grade 3) in 9% of patients; 3 patients (9%) experienced severe hepatotoxicity. Although indicine N-oxide has some antileukemic activity in ALL and is safe at the doses used in this study, the antileukemic activity is significantly less at these two doses than at greater than or equal to 3,000 mg/m2/days for 5 consecutive days. Unfortunately, when the higher doses are administered to children, they are associated with an unacceptably high incidence of severe, irreversible hepatotoxicity.
在一项II期研究中，我们使用氧化印防己毒素治疗了31例急性淋巴细胞白血病（ALL）患儿、14例复发的急性非淋巴细胞白血病（ANLL）患儿以及1例处于急变期（普通急性淋巴细胞白血病抗原阴性）的慢性粒细胞白血病（CML）患儿。在两个剂量水平评估了该药物的疗效和毒性：连续5天2000mg/m²/天（14例患者）和连续5天2500mg/m²/天（17例患者）。每个剂量水平各有1例ALL患者分别获得了持续6个月和1个月的完全缓解（CR）。CML患者获得了持续4个月的部分缓解。ANLL患者均未达到CR。63%的患者肝毒性为轻度（1级或2级），9%为中度（3级）；3例患者（9%）出现严重肝毒性。虽然氧化印防己毒素在ALL中具有一定的抗白血病活性，且在本研究使用的剂量下是安全的，但这两个剂量下的抗白血病活性明显低于连续5天大于或等于3000mg/m²/天的剂量。不幸的是，当给儿童使用更高剂量时，会出现严重的、不可逆的肝毒性，发生率高得令人无法接受。
