Phase I and II study of fludarabine phosphate in leukemia: therapeutic efficacy with delayed central nervous system toxicity.
Phase I and II study of fludarabine phosphate in leukemia: therapeutic efficacy with delayed central nervous system toxicity.
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磷酸氟达拉滨治疗白血病的 I 期和 II 期研究：延迟性中枢神经系统毒性的治疗效果。
DOI：
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发表时间：
1986
影响因子：
45.3
通讯作者：
E. Berman
中科院分区：
文献类型：
--
作者：
R. Warrell;E. Berman
氟达拉宾磷酸(9-β-D-阿拉伯呋喃糖基-2-氟腺嘌呤)是一种新型的嘌呤核苷，在I期临床试验中表现出良好的临床前抗肿瘤活性和毒性。我们评估了氟达拉滨作为持续静脉输注在复发或难治性白血病患者诱导缓解中的临床应用。25例患者接受了30次输液。剂量小于或等于125 mg/m2/d，连续5天，17例患者中只有3例清除了骨髓中的白血病细胞，没有一例获得完全缓解(CR)。9例患者接受150 mg/m2/d治疗5天或125 mg/m2/d治疗7天。其中4例患者达到CR(3例急性非淋巴细胞白血病(ANLL)，1例急性淋巴细胞白血病(ALL))。然而，在两个最高剂量水平下，有5名患者出现了严重的中枢神经系统毒性。最初的神经毒性症状从开始治疗后的21天推迟到43天，包括视神经炎、皮质盲、精神状态改变和全身性癫痫。只有一名患者恢复了视觉和神经功能；其他四名患者经历了进行性神经恶化并死亡。临床病理评估表明，广泛的、严重的脱髓鞘是这些反应的病因。结论：氟达拉滨是诱导急性白血病缓解的有效药物。然而，达到完全缓解所需的剂量与不可接受的中枢神经系统毒性有关。鉴于其强大的抗白血病活性，低剂量氟达拉滨(小于或等于75 mg/m~2/d，连续5天)可能需要与其他化疗药物联合治疗急性白血病患者。
Fludarabine phosphate (9-beta-D-arabinofuranosyl-2-fluoroadenine), a novel purine nucleoside, has demonstrated excellent preclinical antitumor activity and little toxicity in phase I clinical trials. We evaluated the clinical use of fludarabine given as a continuous intravenous (IV) infusion for remission induction in patients with relapsed or refractory leukemia. Thirty infusions were administered to 25 patients. At doses less than or equal to 125 mg/m2/d for five days, only three of 17 patients cleared their bone marrow of leukemic cells, and none achieved complete remission (CR). Nine patients received doses of 150 mg/m2/d for five days or 125 mg/m2/d for seven days. Four of these patients achieved CR (three patients with acute nonlymphoblastic leukemia (ANLL), one patient with acute lymphoblastic leukemia (ALL]. However, severe CNS toxicity was encountered in five patients at the two highest dose levels. Initial symptoms of neurotoxicity were delayed from 21 to 43 days after starting treatment and consisted of optic neuritis, cortical blindness, altered mental status, and generalized seizure. Only one patient regained visual and neurologic function; four other patients experienced progressive neurologic deterioration and died. Clinicopathologic evaluation suggested widespread, severe demyelination as the etiology of these reactions. We conclude that fludarabine is an effective drug for remission induction in acute leukemia. However, doses required to achieve CR are associated with unacceptable CNS toxicity. In view of its potent antileukemic activity, further evaluation of fludarabine at lower doses (less than or equal to 75 mg/m2/d for five days) may be warranted in combination with other chemotherapeutic agents for the treatment of patients with acute leukemia.
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阿糖腺苷治疗肾移植患者巨细胞病毒感染的试验。
影响因子：
--
作者：
Marker,SC;Howard,RJ;Groth,KE;Mastri,AR;Simmons,RL;BalfourJr,HH
通讯作者：
BalfourJr,HH
9-β-D-阿拉伯呋喃糖基-2-氟腺嘌呤 5-单磷酸 (NSC 312887)（一种新型嘌呤抗代谢物）的 I 期临床研究。
影响因子：
11.2
作者：
Hutton,JJ;VonHoff,DD;Kuhn,J;Phillips,J;Hersh,M;Clark,G
通讯作者：
Clark,G
1-(2-脱氧-2-氟-1-β-D-阿拉伯呋喃糖基)-5-甲基尿嘧啶 (FMAU) 的 I 期试验。
DOI：
--
发表时间：
1985
期刊：
Cancer treatment reports
影响因子：
--
作者：
Fanucchi,MP;Leyland-Jones,B;Young,CW;Burchenal,JH;Watanabe,KA;Fox,JJ
通讯作者：
Fox,JJ
极高剂量胸苷输注对白血病和淋巴瘤患者的影响。
影响因子：
11.2
作者：
Blumenreich,MS;Woodcock,TM;Andreeff,M;Hiddemann,W;Chou,TC;Vale,K;O'Hehir,M;Clarkson,BD;Young,CW
通讯作者：
Young,CW
高剂量 1-β-D-阿拉伯呋喃糖基胞嘧啶治疗急性白血病和难治性淋巴瘤的初步研究：临床反应和药理学。
影响因子：
11.2
作者：
Early,AP;Preisler,HD;Slocum,H;Rustum,YM
通讯作者：
Rustum,YM