Eder J P, Elias A D, Ayash L, Wheeler C A, Shea T C, Schnipper L E, Frei E, Antman K H
Department of Medicine, Charles A. Dana Research Institute, Boston, MA.
Cancer Chemother Pharmacol. 1991;29(1):61-5. doi: 10.1007/BF00686337.
Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granulocytopenia of less than 500/microliters that lasted for greater than 14 days or thrombocytopenia of less than 25,000/microliters that lasted for greater than 14 days was the target dose-limiting toxicity in the absence of nonhematologic grade 4 toxicity. The maximal tolerated dose was 7 g/m2. Three patients died. Of 21 evaluable patients, 9 responded, including 8/9 who had experienced disease progression during prior oxazaphosphorine-containing combination chemotherapy. Clinically meaningful responses were observed in patients who had demonstrated clinical resistance to an oxazaphosphorine drug given at lower doses.
在某些动物模型中，当采用分次给药方案时，环磷酰胺显示出增强的杀肿瘤活性，同时骨髓毒性降低。在一项环磷酰胺96小时持续输注的I期试验中，共治疗了22例难治性转移性癌症患者。在无4级非血液学毒性的情况下，持续超过14天的粒细胞减少至低于500/微升或血小板减少至低于25,000/微升是目标剂量限制性毒性。最大耐受剂量为7 g/m²。3例患者死亡。在21例可评估患者中，9例有反应，其中包括9例中有8例在先前含氮芥类的联合化疗期间出现疾病进展。在对较低剂量氮芥类药物表现出临床耐药性的患者中观察到了具有临床意义的反应。
