Spriggs D R, Robbins G, Arthur K, Mayer R J, Kufe D
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Leukemia. 1988 May;2(5):304-6.
High doses of cytosine arabinoside (ara-C) were administered by continuous infusion to 24 patients with acute leukemia in relapse or blast phase of chronic myelogenous leukemia (CML). Ara-C was infused at a dose rate of 250 mg/M2/hr for 36 to 72 hr. The major toxicities were myelosuppression, diarrhea, and abdominal pain. Other toxicities included pulmonary edema, neurotoxicity, and liver function abnormalities. The gastrointestinal toxicity was dose-limiting and a phase II dose was established at 250 mg/M2/hr for 60-72 hr. Four patients treated with this dose schedule had objective responses. Two patients with CML in blast phase returned to chronic phase and have remained stable without maintenance therapy for 12 and 18 months. Two patients with acute myelogenous leukemia in relapse entered complete remissions which continued unmaintained for 4 and 6 months. Steady-state plasma ara-C levels ranged between 7 and 24 x 10(-6) M, while ara-U levels were as high as 4.5 x 10(-4) M. There was no detectable accumulation of ara-C or ara-U during the infusion period. These findings would suggest that the continuous infusion of high dose ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
对24例复发的急性白血病或慢性粒细胞白血病（CML）急变期患者持续输注高剂量阿糖胞苷（ara-C）。阿糖胞苷以250mg/M2/小时的速率输注36至72小时。主要毒性为骨髓抑制、腹泻和腹痛。其他毒性包括肺水肿、神经毒性和肝功能异常。胃肠道毒性是剂量限制性的，II期剂量确定为250mg/M2/小时，持续60 - 72小时。按此剂量方案治疗的4例患者有客观反应。2例CML急变期患者恢复到慢性期，且在未进行维持治疗的情况下分别保持稳定12个月和18个月。2例复发的急性髓性白血病患者进入完全缓解期，未进行维持治疗分别持续了4个月和6个月。稳态血浆阿糖胞苷水平在7至24×10（-6）M之间，而阿糖尿苷水平高达4.5×10（-4）M。在输注期间未检测到阿糖胞苷或阿糖尿苷的蓄积。这些发现表明持续输注高剂量阿糖胞苷可能对治疗急性白血病和CML急变期有用。
