イホスファミド

外観

白色〜わずかにうすい褐色, 結晶性粉末〜粉末

溶解性

メタノール及びエタノール(95)に極めて溶けやすく、水に溶けやすい。

用途

がん研究用試薬

用途

アルキル化剤です。活性代謝 物である 4- ヒドロキシイホスファミド及び アルドイホスファミドが腫瘍細胞の DNA 合 成阻害作用を示します。

効能

抗悪性腫瘍薬, アルキル化剤

商品名

イホマイド (塩野義製薬)

使用上の注意

不活性ガス封入

化学的特性

Crystalline Solid

使用

A cytostatic agent, related structurally to cyclophosphamide

定義

ChEBI: The simplest member of the class of ifosfamides that is 1,3,2-oxazaphosphinan-2-amine 2-oxide substituted by 2-chloroethyl groups on both the nitrogen atoms respectively. It is a nitrogen mustard alkylating agent used in the treatment of advanced breast c ncer.

適応症

Ifosfamide (Ifex) is an analogue of cyclophosphamide that requires metabolic activation to form 4-hydroxyifosfamide. In general, the metabolism, serum half-life, and excretion of ifosfamide are similar to those of cyclophosphamide.
Ifosfamide is active against a broad spectrum of tumors, including germ cell cancers of the testis, lymphomas, sarcomas, and carcinomas of the lung, breast, and ovary. It is thought to be more active than cyclophosphamide in germ cell cancers and sarcomas.
Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. It also may produce alopecia, nausea, vomiting, infertility, and second tumors, particularly acute leukemias. Neurological symptoms including confusion, somnolence, and hallucinations have also been reported. It is recommended that ifosfamide be coadministered with the thiol compound mesna (Mesnex) to avoid hemorrhagic cystitis.

一般的な説明

Ifosfamide is available in 1- and 3-g vials for IV administrationas Food and Drug Administration (FDA)-approvedthird-line therapy in the treatment of testicular cancer. It has also been utilized (although not FDA approved) in the treatmentof a wide variety of cancers including Hodgkin’s andnon-Hodgkin’s lymphoma, soft tissue sarcoma, germ celltumors, small cell lung cancer, non–small cell lung cancer(NSCLC), cancers of the head and neck, bladder cancer, cervicalcancer, and Ewing sarcoma. Coadministration ofmesna is recommended. The mechanisms of resistance areidentical to those seen with cyclophosphamide. The drug iswidely distributed with a low extent of protein binding(20%). Metabolism primarily by CYP3A4/5 and CYP2B6 isrequired for activation of the compound. Theagent is administered as the racemic mixture as a result ofthe presence of the chiral phosphorus atom, and differentialmetabolism of the R- and S-isomers has been observed. Incontrast to cyclophosphamide, there is a greater amount ofdeactivation of the agent by N-dechloroethylation and subsequentlymore chloroacetaldehyde is produced, which mayresult in a greater amount of neurotoxicity and nephrotoxicitythan seen with cyclophosphamide. The N-dechloroethylatedmetabolites are the predominate species seen in theplasma. The parent and metabolites are eliminated inthe urine with an elimination half-life of 3 to 10 hours. Themajor components found in the urine are the dechlorethylatedmetabolites. Dose-limiting toxicities include myelosuppressionand bladder toxicity. Other adverse effectsinclude nausea, alopecia, amenorrhea, inappropriate secretionof antidiuretic hormone, as well as the production ofsecondary cancers. Neurotoxicity, which is associated withthe production of chloroacetaldehyde presents as confusion,seizure, weakness, and hallucination, and coma may occur.

臨床応用

Ifosamide currently is used as “third-line” therapy against testicular cancer, although it also has shown activity in a number of solid tumors and hematologic cancers.

副作用

Patients on ifosfamide (but not cyclophosphamide) commonly exhibit central nervous system (CNS) toxicity. In severe forms, CNS depression can progress to coma and death.