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六甲蜜胺在耐烷化剂卵巢癌中的应用

Hexamethylmelamine in alkylating agent-resistant ovarian carcinoma.

作者信息

Johnson B L, Fisher R I, Bender R A, DeVita V T, Chabner B A, Young R C

出版信息

Cancer. 1978 Nov;42(5):2157-61. doi: 10.1002/1097-0142(197811)42:5<2157::aid-cncr2820420511>3.0.co;2-7.

Abstract

Twenty-one patients with advanced ovarian cancer proven resistant to standard alkylating chemotherapy were evaluated in a prospective study of Hexamethylmelamine. All but three patients received 8 mg/kg daily with dose modifications appropriate to the degree of toxicity; the latter three patients were treated on an intermittent 14 day course of 8 mg/kg daily. Six patients (28%) experienced an objective response with a median duration of 2.5 months (range 1--5 months). The toxic effects requiring dose modification were gastrointestinal in 57%, hematologic in 62%, and neurologic in 28.5%. An average of 60.5% of the total projected dose was tolerated for a median of 44 days (range 7--113). Twelve patients (57%) experienced severe toxicity requiring discontinuation of therapy. It is apparent from this study that Hexamethylmelamine is an active agent in ovarian cancer and is not invariably cross-resistant to conventional alkylating agent therapy. These two characteristics make it an attractive agent for use in combination. Its toxicity in previously treated patients in the schedules used here, however, is substantial.

摘要

在一项关于六甲蜜胺的前瞻性研究中,对21例经证实对标准烷化剂化疗耐药的晚期卵巢癌患者进行了评估。除3例患者外,所有患者均接受每日8mg/kg的剂量,并根据毒性程度进行剂量调整;后3例患者接受为期14天的间歇性治疗,每日剂量为8mg/kg。6例患者(28%)出现客观缓解,中位缓解持续时间为2.5个月(范围1-5个月)。需要调整剂量的毒性反应中,胃肠道反应占57%,血液学反应占62%,神经学反应占28.5%。平均有60.5%的预计总剂量被耐受,中位耐受时间为44天(范围7-113天)。12例患者(57%)出现严重毒性反应,需要停止治疗。从这项研究可以明显看出,六甲蜜胺是卵巢癌的一种有效药物,并非总是与传统烷化剂治疗产生交叉耐药。这两个特性使其成为一种有吸引力的联合用药。然而,在此处使用的方案中,它对先前接受过治疗的患者的毒性很大。

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