TROFOSFAMIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C9H18Cl3N2O2P
Molecular Weight	323.584
Optical Activity	( + / - )
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClCCN(CCCl)P1(=O)OCCCN1CCCl

InChI

InChIKey=UMKFEPPTGMDVMI-UHFFFAOYSA-N

InChI=1S/C9H18Cl3N2O2P/c10-2-6-13-5-1-9-16-17(13,15)14(7-3-11)8-4-12/h1-9H2

HIDE SMILES / InChI

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/trofosfamide | https://www.baxter.de/sites/g/files/ebysai1301/files/2019-01/ixoten_fs.pdf | https://www.ncbi.nlm.nih.gov/pubmed/15591719

Trofosfamide is an orally bioavailable antineoplastic agent. Upon administration, it is predominantly metabolized to the cyclophosphamide analog ifosfamide, which is then metabolized by liver cytochrome P450s to the active isophosphoramide mustard (IPM). IPM alkylates DNA to form DNA-DNA cross-links, which may result in inhibition of DNA, RNA and protein synthesis, and tumor cell apoptosis. Trofosfamide is marketed in Germany by Baxter under tradename Ixoten. It is indicated for the treatment of non-Hodgkin's lymphoma after failure of the standard therapy. The drug was investigated in the clinical trials against soft tissue sarcoma and melanoma.

Approval Year

PubMed

Title	Date	PubMed
[Cyclophosphamide and bladder carcinoma (case report) (author's transl)].	1978 Jan 6	620650
Studies on the urotoxicity of oxazaphosphorine cytostatics and its prevention--I. Experimental studies on the urotoxicity of alkylating compounds.	1981 Jun	7308258
Palliative chemotherapy in pretreated patients with advanced cancer: oral trofosfamide is effective in ovarian carcinoma.	2001	11768034
Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours.	2001 Jun 1	11384092
Sensitive gas chromatographic determination of the cyclophosphamide metabolite 2-dechloroethylcyclophosphamide in human plasma.	2001 Jun 15	11417881
Cyclophosphamide and related anticancer drugs.	2001 Nov 25	11817027
Trofosfamide as salvage therapy for anaplastic large cell lymphoma relapsing after high-dose chemotherapy.	2002 Dec	12613523
High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma.	2002 Dec	12476282
Treatment of paediatric pontine glioma with oral trophosphamide and etoposide.	2002 Oct 21	12434281
Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors.	2003 Nov 15	14601096
Antiangiogenic therapy with pioglitazone, rofecoxib, and trofosfamide in a patient with endemic kaposi sarcoma.	2004 Dec	15611430
Trofosfamide in the palliative treatment of cancer: a review of the literature.	2004 Dec	15591719
Dose escalation study for defining the maximum tolerated dose of continuous oral trofosfamide in pretreated patients with metastatic lung cancer.	2004 Dec	15591711
Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study.	2004 Nov 1	15477864
Pioglitazone and rofecoxib combined with angiostatically scheduled trofosfamide in the treatment of far-advanced melanoma and soft tissue sarcoma.	2004 Nov 15	15470711
Recent developments in salvage chemotherapy for patients with metastatic soft tissue sarcoma.	2005	15631540
Primary dissemination of high-grade gliomas in children: experiences from four studies of the Pediatric Oncology and Hematology Society of the German Language Group (GPOH).	2005 Apr	15925999
Anti-inflammatory and angiostatic therapy in chemorefractory multisystem Langerhans' cell histiocytosis of adults.	2005 Mar	15725096
Insights into oxazaphosphorine resistance and possible approaches to its circumvention.	2005 Oct	16154799
The radiation response of sarcomas by histologic subtypes: a review with special emphasis given to results achieved with razoxane.	2006	17040092
Antiangiogenic therapy in metastatic prostate carcinoma complicated by cutaneous lupus erythematodes.	2006 Aug	16887488
Intraocular lymphoma 2000-2005: results of a retrospective multicentre trial.	2006 Jun	16228920
The Role of PPARs in the Endothelium: Implications for Cancer Therapy.	2008	19043612
PPARgamma and MEK Interactions in Cancer.	2008	18596912
Potential combination chemotherapy approaches for advanced adult-type soft-tissue sarcoma.	2008	18572972
Peroxisome Proliferator-Activated Receptor-gamma Ligands: Potential Pharmacological Agents for Targeting the Angiogenesis Signaling Cascade in Cancer.	2008	18464916
A pilot study of docetaxel and trofosfamide as second-line 'metronomic' chemotherapy in the treatment of metastatic non-small cell lung cancer (NSCLC).	2008 Apr	18418020
A pharmacokinetic and pharmacodynamic study on metronomic irinotecan in metastatic colorectal cancer patients.	2008 Apr 22	18362940
Infraorbital cutaneous angiosarcoma: a diagnostic and therapeutic dilemma.	2008 Aug 11	18694495
Clinical benefit of second-line palliative chemotherapy in advanced soft-tissue sarcoma.	2010	20508840
Metronomic treatment with low-dose trofosfamide leads to a long-term remission in a patient with docetaxel-refractory advanced metastatic prostate cancer.	2010	20396674
Oxazaphosphorines: new therapeutic strategies for an old class of drugs.	2010 Aug	20446865

Patents

Name

Type

Language

TROFOSFAMIDE

Official Name

English

NSC-109723

Code

English

Trofosfamide [WHO-DD]

Common Name

English

TROFOSFAMIDE [MI]

Common Name

English

TROFOSFAMIDE [MART.]

Common Name

English

A-4828

Code

English

trofosfamide [INN]

Common Name

English

3-(2-CHLOROETHYL)-2-(BIS(2-CHLOROETHYL)AMINO)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORIN 2-OXIDE

Systematic Name

English

Z-4828

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C697