Cyclophosphamide and cancer: golden anniversary

被引：729

作者：

Emadi, Ashkan ^{[1
]}

Jones, Richard J. ^{[2
]}

Brodsky, Robert A. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Div Adult Hematol, Baltimore, MD 21231 USA

[2] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA

来源：

NATURE REVIEWS CLINICAL ONCOLOGY | 2009年 / 6卷 / 11期

关键词：

HIGH-DOSE CYCLOPHOSPHAMIDE; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; ONSET HEMORRHAGIC CYSTITIS; SURGICAL ADJUVANT BREAST; APLASTIC-ANEMIA; NONLINEAR PHARMACOKINETICS; AUTOLOGOUS TRANSPLANTATION; ALDEHYDE DEHYDROGENASE; CARDIAC COMPLICATIONS;

D O I：

10.1038/nrclinonc.2009.146

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cyclophosphamide remains one of the most successful and widely utilized antineoplastic drugs. Moreover, it is also a potent immunosuppressive agent and the most commonly used drug in blood and marrow transplantation (BMT). It was initially synthesized to selectively target cancer cells, although the hypothesized mechanism of tumor specificity (activation by cancer cell phosphamidases) transpired to be irrelevant to its activity. Nevertheless, cyclophosphamide's unique metabolism and inactivation by aldehyde dehydrogenase is responsible for its distinct cytotoxic properties. Differential cellular expression of aldehyde dehydrogenase has an effect on the anticancer therapeutic index and immunosuppressive properties of cyclophosphamide. This Review highlights the chemistry, pharmacology, clinical toxic effects and current clinical applications of cyclophosphamide in cancer and autoimmune disorders. We also discuss the development of high-dose cyclophosphamide for BMT and the treatment of autoimmune diseases.

引用

页码：638 / 647

页数：10

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