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
Trofosfamide as salvage therapy for anaplastic large cell lymphoma relapsing after high-dose chemotherapy.	2002 Dec	12613523
Relapse after high-dose therapy in relapsed Ewing's tumor patients: effects of maintenance chemotherapy in two selected patients?	2003 Dec	14709933
[Hypoglycemia associated with the production of insulin-like growth factor (IGF)-II by a hemangiopericytoma].	2003 Feb 7	12571793
Phase II trial of trofosfamide in patients with advanced pretreated soft tissue sarcomas.	2003 Mar-Apr	12820475
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
Hypersensitivity pneumonitis associated with the use of trofosfamide.	2004 Jul	15205604
Investigations on the pharmacokinetics of trofosfamide and its metabolites-first report of 4-hydroxy-trofosfamide kinetics in humans.	2004 Jun	15138712
Enzyme-catalyzed activation of anticancer prodrugs.	2004 Mar	15001663
Metronomic scheduling of trofosfamide chemotherapy in human NSCLC xenografts highly increases therapeutic efficacy compared to conventional scheduling by inhibition of angiogenesis.	2004 Nov	15598036
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
Treatment of primary intraocular lymphoma with oral trofosfamide: report of two cases and review of the literature.	2004 Sep	15349786
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
A new therapeutic approach in patients with advanced sarcoma.	2005 Dec	16369750
Pharmacokinetics and efficacy of ifosfamide or trofosfamide in patients with intraocular lymphoma.	2005 Dec	16219622
[Metronomic chemotherapy. Should we change our thinking in the treatment of advanced tumors?].	2005 Jan	16353744
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
Reversal of resistance to oxazaphosphorines.	2006 Aug	16918308
Antiangiogenic therapy in metastatic prostate carcinoma complicated by cutaneous lupus erythematodes.	2006 Aug	16887488
Palliative chemotherapy with trofosfamide in advanced prostate cancer.	2006 Jan-Feb	16739316
Intraocular lymphoma 2000-2005: results of a retrospective multicentre trial.	2006 Jun	16228920
Metronomic trofosfamide inhibits progression of human lung cancer xenografts by exerting anti-angiogenic effects.	2006 Oct	16761121
Secondary dissemination in children with high-grade malignant gliomas and diffuse intrinsic pontine gliomas.	2006 Oct 23	17047647
Complete remission of relapsing high-grade angiosarcoma with single-agent metronomic trofosfamide.	2006 Sep	16940811
Design of new oxazaphosphorine anticancer drugs.	2007	17430192
Simultaneous determination of gemcitabine, taxol, cyclophosphamide and ifosfamide in wipe samples by high-performance liquid chromatography/tandem mass spectrometry: protocol of validation and uncertainty of measurement.	2007	17340557
Recurrent low- to intermediate-grade chondrosarcoma of the thumb with lung metastases: an objective response to trofosfamide.	2007 Apr	17396043
Systemic treatment options for patients with refractory adult-type sarcoma beyond anthracyclines.	2007 Mar	17264755
Thyroid function in paediatric and young adult patients after sarcoma therapy: a report from the Late Effects Surveillance System.	2007 May	17381483
Diagnosis and management of primary intraocular lymphoma: an update.	2007 Sep	19668478
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
Infraorbital cutaneous angiosarcoma: a diagnostic and therapeutic dilemma.	2008 Aug 11	18694495
Low-dose oral metronomic chemotherapy prevents mobilization of endothelial progenitor cells into the blood of cancer patients.	2008 Nov-Dec	19181016
Ifosfamide or trofosfamide in patients with intraocular lymphoma.	2009 Jun	19099202
Principles of modular tumor therapy.	2009 Sep	19593676
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
Sclerosing epithelioid fibrosarcoma of the bone: a case report of high resistance to chemotherapy and a survey of the literature.	2010	20396630
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