Page last updated: 2024-12-06

trofosfamide

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Trofosfamide is a synthetic alkylating agent, structurally similar to ifosfamide. It is a prodrug that is converted in the body to its active metabolite, tetrahydro-N,N-bis(2-chloroethyl)-phosphorodiamidic acid. This metabolite acts as a DNA cross-linking agent, inhibiting DNA replication and cell division. Trofosfamide is used in the treatment of various types of cancers, including ovarian cancer, breast cancer, and soft tissue sarcomas. It is particularly effective in treating high-grade malignant gliomas, a type of brain cancer. Research on trofosfamide is ongoing, focusing on its potential use in combination therapies with other drugs, as well as exploring ways to improve its therapeutic efficacy and minimize side effects. Trofosfamide is studied due to its potent antitumor activity and unique pharmacological properties, making it a promising candidate for the treatment of various cancers.'

trofosfamide: cyclophosphamide analog; structure [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID65702
CHEMBL ID462019
CHEBI ID135381
SCHEMBL ID8236
MeSH IDM0044822

Synonyms (78)

Synonym
smr001570883
nsc314927
nsc-314927
nsc314928
2h-1,2-oxazaphosphorin-2-amine, n,n,3-tris(2-chloroethyl)tetrahydro-, 2-oxide, (+)-
nsc-314928
2h-1,2-oxazaphosphorin-2-amine, n,n,3-tris(2-chloroethyl)tetrahydro-, 2-oxide, (-)-
einecs 244-770-8
n,n,3-tris(2-chloroethyl)tetrahydro-2h-1,3,2-oxazaphosphorin-2-amine 2-oxide
n,n-3'-tris(2-chloroethyl)tetrahydro-2h-1,3,2-oxazaphosphorin-2-amine, 2-oxide
ccris 4442
3-(2-chloroethyl)-2-(bis(2-chloroethyl)amino)tetrahydro-2h-1,3,2-oxazaphosphorin 2-oxide
brn 0532530
trofosfamide [inn]
2h-1,3,2-oxazaphosphorin-2-amine, n,n,3-tris(2-chloroethyl)tetrahydro-, 2-oxide
3-(2-chloroethyl)-2-(bis(2-chloroethyl)amino)perhydro-2h-1,3,2-oxazaphosphorine 2-oxide
2-(bis(2-chloroethyl)amino)-3-(2-chloroethyl)tetrahydro-2h-1,3,2-oxazaphosphorine 2-oxide
trofosfamido [inn-spanish]
nsc 109723
2h-1,3,2-oxazaphosphorine, 2-(bis(2-chloroethyl)amino)-3-(2-chloroethyl)tetrahydro-, 2-oxide
n,n,n'-tris(2-chloraethyl)-n',o-propylen-phosphorsaureester-diamid [german]
trofosfamida [spanish]
trofosfamidum [inn-latin]
n,n,n'-tris(2-chloroethyl)-n',o-propylene phosphoric acid ester diamide
trofosfamide (inn)
D07252
2h-1,2-oxazaphosphorine, 2-[bis(2-chloroethyl)amino]-3-(2-chloroethyl)tetrahydro-, 2-oxide
trophosphamid
3-(2-chloroethyl)-2-[bis(2-chloroethyl)amino]perhydro-2h-1,2-oxazaphosphorine 2-oxide
nsc109723
22089-22-1
trisfosfamide
ixoten
trofosfamide
z 4828
cyclophosphamide, n-monochloroethyl derivative
asta z 4828
2h-1,2-oxaphosphorin-2-amine, tetrahydro-n,n,3-tris(2-chloroethyl)-, 2-oxide
nsc-109723
trofosfamid
trophosphamide
mls002704177 ,
2h-1,2-oxazaphosphorin-2-amine, n,n,3-tris(2-chloroethyl)tetrahydro-, 2-oxide
TFF ,
z-4828 ,
trilofosfamida
triphosphamide
trifosfamide
trilophosphamide
a-4828 ,
CHEBI:135381
CHEMBL462019
n,n,n'-tris(2-chloraethyl)-n',o-propylen-phosphorsaureester-diamid
trofosfamidum
trofosfamido
h64jru6gj0 ,
cyclophosphamide, n-monochloroethyl deriv.
unii-h64jru6gj0
trofosfamida
FT-0675702
trofosfamide [mi]
trofosfamide [mart.]
trofosfamide [who-dd]
SCHEMBL8236
MLS006010763
UMKFEPPTGMDVMI-UHFFFAOYSA-N
n,n,3-tris(2-chloroethyl)-2-oxo-1,3,2lambda5-oxazaphosphinan-2-amine
AKOS030255922
J-014484
DB12902
HY-119824
2-(bis(2-chloroethyl)amino)-3-(2-chloroethyl)-1,3,2-oxazaphosphinane 2-oxide
Q10384947
DTXSID60865031
BRD-A91386192-001-04-0
CS-0078076
XAA08922
?trofosfamide

Research Excerpts

Overview

Torfosfamide is an orally applicable, well-tolerated and cost-effective drug that works in patients with advanced NSCLC. It is an alkylating agent that is derived from the oxazaphoshorines.

ExcerptReferenceRelevance
"Trofosfamide is an orally applicable, well-tolerated and cost-effective drug that works in patients with advanced NSCLC, who have undergone at least 2 lines of therapy. "( Old wine in new pipes? Treatment of advanced non-small cell lung cancer with trofosfamide.
Reißig, A; Walther, M, 2013
)
2.06
"Trofosfamide is an alkylating agent that is derived from the oxazaphoshorines. "( Trofosfamide in the palliative treatment of cancer: a review of the literature.
Frank, R; Latz, D; Nassar, N, 2004
)
3.21
"Trofosfamide is an interesting and a non-toxic palliative treatment for relapsing malignant lymphomas especially in elderly patients."( Trofosfamide as a salvage treatment with low toxicity in malignant lymphoma. A phase II study.
Helsing, MD, 1997
)
2.46
"Trofosfamide (TROFO) is an orally taken oxazaphosphorine prodrug."( Trofosfamide in patients with pancreatic cancer.
Dageförde, J; Klapdor, R; Schmidt-Sandte, W; Wagner, T; Wiedemann, GJ,
)
2.3

Effects

ExcerptReferenceRelevance
"Trofosfamide has some activity in hormone-refractory advanced prostate cancer. "( Palliative chemotherapy with trofosfamide in advanced prostate cancer.
Nikkanen, V; Salminen, EK; Sundström, J,
)
1.87

Treatment

ExcerptReferenceRelevance
"Treatment with trofosfamide in this combination setting was generally well tolerated with no treatment-related deaths and manageable side effects, most of which were WHO class I-II; the most clinically relevant toxicity was cytopenia. "( Trofosfamide in the treatment of elderly or frail patients with diffuse large B-cell lymphoma.
Bartscht, T; Biersack, H; Fetscher, S; Gebauer, N; Lehnert, H; Mayer, T; Merz, H; Rades, D; Riecke, A; Witte, HM, 2019
)
2.31

Toxicity

ExcerptReferenceRelevance
" Together with previous findings published in the literature, where the same doses induced heritable genetic damage, this study demonstrates a marked adverse cytotoxic effect of TP on the male reproductive integrity."( Flow cytometric assessment of trophosphamide toxicity on mouse spermatogenesis.
Bartoleschi, C; Cordelli, E; Leter, G; Pacchierotti, F; Spanò, M; Tiveron, C, 1996
)
0.29
" Main toxicity was leukopenia (36% grade III or IV), whereas grade III/IV non-hematological adverse events did not occur."( Low-dose trofosfamide plus rituximab is an effective and safe treatment for diffuse large B-cell lymphoma of the elderly: a single center experience.
Herr, W; Reichle, A; Schelker, RC; Vogelhuber, M, 2018
)
0.9

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic data of ifosfamide and its metabolites in these cases are scanty."( Gas chromatographic determination of ifosfamide in microvolumes of urine and plasma.
Beijnen, JH; Bult, A; de Kraker, J; Kaijser, GP; Underberg, WJ; Wiese, G, 1991
)
0.28
" Pharmacokinetic parameters were normalized to a dosage of 100 mg/m2."( [Pharmacokinetic aspects of oral administration of etoposide].
Boos, J; Hempel, G; Jürgens, H; Krümpelmann, S; Schulze-Westhoff, P; Tillmann, B; Wagner, A; Würthwein, G,
)
0.13
"A fast metabolism of TRO with a half-life of about 1 h was observed."( New insights into the clinical pharmacokinetics of trofosfamide.
Brinker, A; Brüggemann, SK; Kisro, J; Letsch, C; Wagner, T, 2002
)
0.57
" With a short apparent half-life (1."( Investigations on the pharmacokinetics of trofosfamide and its metabolites-first report of 4-hydroxy-trofosfamide kinetics in humans.
Baumann, F; Niederwieser, D; Niemeyer, U; Pönisch, W; Preiss, R; Stefanovic, D, 2004
)
0.59

Compound-Compound Interactions

ExcerptReferenceRelevance
"A Phase II trial was initiated to analyze the activity of a continuously administered molecularly targeted treatment regimen (daily pioglitazone [45 mg administered orally] and rofecoxib [25 mg administered orally]) combined with sequentially added angiostatic chemotherapy for patients with previously treated metastatic melanoma (n = 19) or soft tissue sarcoma (n = 21)."( Pioglitazone and rofecoxib combined with angiostatically scheduled trofosfamide in the treatment of far-advanced melanoma and soft tissue sarcoma.
Andreesen, R; Bataille, F; Berand, A; Bross, K; Krause, SW; Reichle, A; Vogt, T; Wild, P, 2004
)
0.56

Bioavailability

ExcerptReferenceRelevance
"The bioavailability of orally administered sodium 2-mercaptoethane sulfonate (mesna, Uromitexan drink ampoules) was tested in 18 healthy probands and in 5 tumor patients."( Bioavailability of orally administered mesna.
Breuel, HP; Burkert, H; Lücker, PW; Wetzelsberger, N, 1984
)
0.27
" Bioavailability of TRO could not be calculated directly, because TRO is only available as an oral formulation."( New insights into the clinical pharmacokinetics of trofosfamide.
Brinker, A; Brüggemann, SK; Kisro, J; Letsch, C; Wagner, T, 2002
)
0.57
" The bioavailability is nearly 100% after oral application, and the main metabolites are 4-hydroxytrofosfamide, and 4-hydroxyifosfamide."( Hypersensitivity pneumonitis associated with the use of trofosfamide.
Hartmann, JT; Kanz, L; Kopp, HG, 2004
)
0.79

Dosage Studied

ExcerptRelevanceReference
" The dose-response for MN induction was linear at all time intervals studied, except for 18 days time point."( Detection of germ cell mutagenicity of trophosphamide by the spermatid micronucleus test in the rat.
Lähdetie, J; Suutari, A; West, A, 1995
)
0.29
" The influence of the dosage of etoposide on its activity and toxicity ("schedule dependency") has also been discussed."( [Pharmacokinetic aspects of oral administration of etoposide].
Boos, J; Hempel, G; Jürgens, H; Krümpelmann, S; Schulze-Westhoff, P; Tillmann, B; Wagner, A; Würthwein, G,
)
0.13
"Sixteen patients aged between 3 and 73 years received oral etoposide at a dosage of 28 mg/m2 to 149 mg/m2 in combination with oral trofosfamide for palliation."( [Pharmacokinetic aspects of oral administration of etoposide].
Boos, J; Hempel, G; Jürgens, H; Krümpelmann, S; Schulze-Westhoff, P; Tillmann, B; Wagner, A; Würthwein, G,
)
0.34
" Pharmacokinetic parameters were normalized to a dosage of 100 mg/m2."( [Pharmacokinetic aspects of oral administration of etoposide].
Boos, J; Hempel, G; Jürgens, H; Krümpelmann, S; Schulze-Westhoff, P; Tillmann, B; Wagner, A; Würthwein, G,
)
0.13
" On simulating different dosage schedules, it was seen that the duration of intermediate concentrations (0."( [Pharmacokinetic aspects of oral administration of etoposide].
Boos, J; Hempel, G; Jürgens, H; Krümpelmann, S; Schulze-Westhoff, P; Tillmann, B; Wagner, A; Würthwein, G,
)
0.13
" The idea of angiostatic therapy following the paradigm of metronomic dosed chemotherapeutics combined with proapoptotic biomodulators had not been considered previously in these patients."( Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors.
Andreesen, R; Bataille, F; Berand, A; Bross, K; Hafner, C; Jauch, KW; Landthaler, M; Reichle, A; Vogt, T, 2003
)
0.55
" Metronomically, dosed oral chemotherapy provides a convenient treatment option and surprisingly high response rates have been published for small patient groups."( Complete remission of relapsing high-grade angiosarcoma with single-agent metronomic trofosfamide.
Hartmann, JT; Kanz, L; Kopp, HG, 2006
)
0.56
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
ifosfamidesCompounds containing an ifosfamide skeleton.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (14)

Assay IDTitleYearJournalArticle
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID409956Inhibition of mouse brain MAOB2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID409954Inhibition of mouse brain MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID1197742Stimulation of human OATP1B1-mediated [3H]estrone 3-sulfate at 100 uM after 5 mins relative to control2015European journal of medicinal chemistry, Mar-06, Volume: 92Interaction of human organic anion transporter polypeptides 1B1 and 1B3 with antineoplastic compounds.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (111)

TimeframeStudies, This Drug (%)All Drugs %
pre-199025 (22.52)18.7374
1990's25 (22.52)18.2507
2000's41 (36.94)29.6817
2010's16 (14.41)24.3611
2020's4 (3.60)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.28

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index25.28 (24.57)
Research Supply Index4.97 (2.92)
Research Growth Index4.46 (4.65)
Search Engine Demand Index31.58 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.28)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials23 (19.17%)5.53%
Reviews9 (7.50%)6.00%
Case Studies16 (13.33%)4.05%
Observational0 (0.00%)0.25%
Other72 (60.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (4)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Randomised Phase-III Trial of the Cooperative Weichteilsarkom Study Group (CWS) for Localised High-risk Rhabdomyosarcoma and Localised Rhabdomyosarcoma-like Soft Tissue Sarcoma in Children, Adolescents, and Young Adults [NCT00876031]Phase 3195 participants (Actual)Interventional2009-07-01Completed
Therapy-Optimization Trial and Phase II Study for the Treatment of Relapsed or Refractory of Primitive Neuroectodermal Brain Tumors and Ependymomas in Children and Adolescents [NCT00749723]Phase 2/Phase 3174 participants (Actual)Interventional2006-02-01Completed
Randomized Phase II Trial of Trofosfamide vs. Adriamycin in Elderly Patients With Previously Untreated Metastatic Soft Tissue Sarcoma [NCT00204568]Phase 2117 participants (Anticipated)Interventional2004-08-31Active, not recruiting
A Prospective Phase I and Consecutive Phase II, Two-arm, Randomized Multi-center Trial of Temsirolimus in Combination With Pioglitazone, Etoricoxib and Metronomic Low-dose Trofosfamide Versus Dacarbazine (DTIC) in Patients With Advanced Melanoma [NCT01614301]Phase 1/Phase 2136 participants (Anticipated)Interventional2012-05-31Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]