Delving into the Latest Updates on Trofosfamide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

DNA

Action

inhibitors

Mechanism

DNA inhibitors(DNA inhibitors), DNA alkylating agents

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization-

Active Organization-

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC9H18Cl3N2O2P

InChIKeyUMKFEPPTGMDVMI-UHFFFAOYSA-N

CAS Registry22089-22-1

A prospective phase I and consecutive phase II, twoarm, randomized multi-center trial of temsirolimus in combination with pioglitazone, etoricoxib and metronomic low-dose trofosfamide versus dacarbazine (DTIC) in patients with advanced melanoma
Phase I: To determine the dose of temsirolimus to be used in phase II part of the study
Phase II:
To determine overall survival Secondary objectives
To evalulate response rate
To evaluate time to progression (TTP)
To evalulate time to partial response (time to PR or better)(TPR)
To evaluate quality of life
To evaluate tolerability and safety

Start Date01 May 2012

Sponsor / Collaborator

University of Regensburg

[+1]

NCT00876031

/ CompletedPhase 3IIT

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

The purpose of this study is to investigate whether the addition of oral maintenance chemotherapy with O-TIE (Etoposide, Idarubicin, Trofosfamide) for 6 months improves the event free survival (EFS) in patients with localised high-risk RMS and RMS-like Soft Tissue Sarcoma.

Start Date01 Jul 2009

Sponsor / Collaborator

University Hospital Tübingen

[+1]

NCT00749723

/ CompletedPhase 2/3IIT

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

The purpose of this study is to improve overall survival while maintaining a good quality of life in pediatric patients with refractory or recurrent brain tumors (medulloblastomas, supratentorial PNETs, ependymomas WHO grade II and III). Response to different chemotherapy options (intravenous versus oral chemotherapy, intraventricular chemotherapy) as part of a multimodal therapy will be assessed. Progression-free, overall survival and toxicity will be evaluated additionally.

Start Date01 Feb 2006

Sponsor / Collaborator

Universitätsklinikum Bonn

100 Clinical Results associated with Trofosfamide

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100 Translational Medicine associated with Trofosfamide

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100 Patents (Medical) associated with Trofosfamide

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251

Literatures (Medical) associated with Trofosfamide

01 Dec 2024·eClinicalMedicine

Maintenance therapy with trofosfamide, idarubicin and etoposide in patients with rhabdomyosarcoma and other high-risk soft tissue sarcomas (CWS-2007-HR): a multicentre, open-label, randomised controlled phase 3 trial

Article

Author: Schmid, Irene ; Behnisch, Wolfgang ; Bielack, Stefan ; Vokuhl, Christian ; Blattmann, Claudia ; Ljungman, Gustaf ; Blank, Bernd ; Hallmen, Erika ; Niggli, Felix ; Handgretinger, Rupert ; Boos, Joachim ; Müller, Hermann L ; Klingebiel, Thomas ; von Kalle, Thekla ; Teichert von Lüttichau, Irene ; Zimmermann, Martin ; Kazanowska, Bernarda ; Koscielniak, Ewa ; Sparber-Sauer, Monika ; Scheer, Monika ; Ladenstein, Ruth ; Fröhlich, Birgit

BackgroundRhabdomyosarcoma and other soft tissue sarcomas (STS) with high-risk features are still associated with an unsatisfactory outcome. We evaluated the efficacy of oral maintenance therapy added at the end of standard therapy in patients with high-risk rhabdomyosarcoma and STS.MethodsCWS-2007-HR was a multicentre, open-label, randomised controlled, phase 3 trial done at 87 centers in 5 countries. Eligible patients were those aged 6 months to 21 years with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring in unfavourable sites with unfavourable age (≥10 years) and/or tumour size (>5 cm); all non-metastatic alveolar rhabdomyosarcoma and those with any non-metastatic rhabdomyosarcoma with nodal involvement. A further group was also eligible: patients with non-metastatic undifferentiated sarcoma, extraskeletal Ewing sarcoma and primary unresected synovial sarcoma. Patients in complete remission at the end of standard therapy (nine cycles of ifosfamide, vincristine with doxorubicine or dactinomycin, and surgery or radiotherapy, or both) were randomised to either stop treatment (S-arm) or to receive oral maintenance therapy (M-arm) with eight 10-day courses (25 weeks) of trofosfamide (2 × 75 mg/m²/day) and idarubicin (1 × 5 mg/m²/day 1,4,7,10) alternating with trofosfamide and etoposide (2 × 25 mg/m²/day). The primary outcome was event-free survival (EFS) and the secondary outcome was overall survival (OS) in the intent-to treat population. This trial is registered at ClinicalTrials.gov, NCT00876031, and, EudraCT 2007-0001478-10.FindingsBetween July 1st, 2009 and June 30th, 2019, 195 patients were randomly assigned to the M-arm (n = 96) or S-arm (n = 99). In the intent-to-treat population, with a median follow-up of 5.2 years (IQR 3.9-6.1) for surviving patients, the 3-year EFS in the M-arm was 66.9% (95% CI 58.1-77.2) versus 75.6% (67.6-84.6) in the S-arm (hazard ratio, (HR) 1.62, 95% CI 0.98-2.69, p = 0.06). 3-year OS was 82.8% (95% CI 75.4-90.8) in the M-arm versus 84.7% (95% CI 77.8-92.1) in the S-arm (HR 1.55, 95% CI 0.84-2.89, p = 0.17). Grade 3-4 adverse events were haematological in 66% of patients, febrile infections in 6%, gastrointestinal in 10%, and sensory neuropathy in 1%.InterpretationThe addition of 25 weeks of oral maintenance therapy with trofosfamide, etoposide and idarubicin after standard therapy does not improve EFS and OS in patients with high-risk rhabdomyosarcoma and other STS.FundingDeutsche Kinderkrebsstiftung Grant No.DKS 2009.09, DKS 2012.06, DKS 2015.13, DKS 2018.10 and DKS 2021.04.

01 Jun 2024·eJHaem

Treatment sequencing and impact of number of treatment lines on survival in follicular lymphoma: A national population‐based study

Article

Author: Oksanen, Anna ; Wahlin, Björn E ; Smedby, Karin E. ; Andersson, Per‐Ola ; Kimby, Eva ; Wästerlid, Tove ; Spångberg, Linn Deleskog ; Dietrich, Caroline E. ; Enblad, Gunilla

AbstractFollicular lymphoma (FL) is a clinically heterogeneous disease. The need for treatment, treatment sequencing, number of treatment lines, and its association with survival have not been described in a population‐based setting. We identified all patients diagnosed with FL in the Swedish Lymphoma register from 2007 to 2014, followed until 2020, with detailed data on progression/relapse, transformation, and 2nd and further lines of therapy. During a median follow‐up of 6.8 years, 1226 patients (69%) received 1st systemic treatment, 358 patients (20%) were managed with watch‐and‐wait (WaW) only, and 188 (10%) patients were treated with radiotherapy and did not require additional therapy during the study period. Among patients starting systemic treatment, 496 (40%), 224 (18%), and 88 (7%) received 2nd‐, 3rd‐, or 4th‐line therapy, respectively. The 10‐year cause‐specific cumulative incidence of transformation was 13%. Among patients managed with 1st line R‐single, R‐CHOP, or BR, 54%, 33%, and 29% required 2nd line, respectively. The cumulative probability of starting subsequent treatment within 2 years was 26% after 1st line and 35% after 2nd line treatment. Two‐year OS following 1st, 2nd, 3rd, and 4th line systemic treatment was 84%, 70%, 52%, and 36%, respectively, and remained similar when excluding transformations. We conclude that a substantial proportion of FL patients can be managed with WaW for a long period of time, while patients who require multiple treatment lines constitute a group with a large clinical unmet need. These results constitute valuable real‐world reference data for FL.

01 Feb 2024·Journal of Mathematical Chemistry

Identification of potential oral cancer drugs as Bcl-2 inhibitors from known anti-neoplastic agents through docking studies

Author: Pal, Debnath ; Raychaudhury, Chandan ; Srinivasan, Shreyaa

Oral Cancer is one of the major killers in India and of global concern.An attempt has been made here to identify small mol. inhibitors of Bcl-2 (B-cell lymphoma 2) protein through docking studies in search of new oral cancer drugs from a curated set of 276 known anti-neoplastic agents obtained from PubChem.The Bcl-2 protein (PDB id:6QGH), being complexed with ligand ABT-263, has been detached from the complex.The ligand-free protein and 276 compounds have been prepared for docking studies using corresponding tools available in Discovery Studio (DS), ver.4.1.The 276 compounds have been docked on the first site of the protein using LibDock docking program available in DS.By considering Methotrexate as the reference compound (LibDock score: 114.76), we have identified 25 compounds as the most potential oral cancer drugs having LibDock scores greater than 100.Another set of 114 compounds with LibDock scores between 80 and 100 have also been identified as the next set of potential drug candidates and some of them show anti-apoptosis properties.Two other compounds with LibDock scores below 80 have been identified for comparative analyses with some high-scoring compoundsThe docking results have been given in tables and pictures (screenshots) of the docked poses of selected compounds have been shown to illustrate the findings.Finally, the most suitable potential compounds have been identified by applying Lipinski′s Rule of 5.The present approach using known anti-neoplastic agents is believed to help discover potential anti-oral cancer drug candidates.

100 Deals associated with Trofosfamide

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Trofosfamide	L01AA07	DB12902

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Neoplasms	-	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


P11.66 (EANO2023)	Not Applicable	Recurrent Glioblastoma	22	Trofosfamide plus Etoposide	lkagrseslk(gxwvzxesrc) = observed in 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (15/16, 94%) pgcerqkqav (ojoyzptidf ) View more	Positive	08 Sep 2023
				Trofosfamide (Control Group)
CTNI-43 (SNO2022)	Not Applicable	Glioma	33	Trofosfamide plus Etoposide	uoplkzndyl(szrsljqqic) = 21 (64%) of all recurrent glioma patients with hematotoxicity comprising most adverse events (n = 18, 86%; Lymphopenia: n=13, 62%) btpdlonzac (nrahafysal ) View more	Positive	14 Nov 2022
				Trofosfamide (Control Group)
P17.04.B (EANO2022)	Not Applicable	Recurrent Glioma	33	Trofosfamide/Etoposide Combination	knnkayfiaf(rwisozolij) = High-grade adverse events (CTCAE grade≥III) in 21 (64%) of all recurrent glioma patients with hematotoxicity comprising most adverse events (n=18, 86%). Lymphopenia was by far the most observed hematotoxic adverse event (n=13, 62%) dwougvrxyd (woouovphbz ) View more	Positive	05 Sep 2022
				Trofosfamide (Control Group)
CWS-2007HR (ASCO2022) Manual	Phase 3	Neoplasms \| Rhabdomyosarcoma	195	trofosfamide+etoposide+idarubicine+trofosfamide	(kugijfasti) = Toxicity grade 3 (no grade 4) in the M-arm was: hematological in 51 %, febrile infection 5%, sensory neuropathy in 1% pts ahxarzmzwt (sknpdsojjs ) View more	Negative	02 Jun 2022
				vincristine+actinomycin D+doxorubicin+ifosfamide
NCT00204568 (Pubmed) Manual	Phase 2	Metastatic Soft Tissue Sarcoma First line	120	trofosfamide	(zhmismcypo) = incjbmtjan yypbonzbeg (wbaohuujxc, 18.0 - 39.1) View more	Positive	01 Jan 2020
				Doxorubicin	(zhmismcypo) = hqkoybaktt yypbonzbeg (wbaohuujxc, 21.2 - 52.8) View more
NCT00204568 (ASCO2018)	Phase 2	Metastatic Soft Tissue Sarcoma First line	-	Trofosfamide	(mjdqzhihdi) = volxancdhk rkkegjxflq (kjmofmdlsa, 1.6 - 20.9) View more	Positive	01 Jun 2018
				Adriamycin	(mjdqzhihdi) = mhnfpvufrb rkkegjxflq (kjmofmdlsa, 2.2 - 14.9%) View more
ERS2013	Not Applicable	Advanced Lung Non-Small Cell Carcinoma	-	Trofosfamide	(dmesugufhb) = duncegimfm olhshwybas (xulzkgikjt, 9.96 - 18.04) View more	Positive	01 Sep 2013
ASCO2008	Not Applicable	Intraocular Lymphoma	10	Ifosfamide	cimmqfmkwz(juyifbzkng) = Acute toxicity was mainly hematologic shlvjhcaor (aufqsqzzhw ) View more	-	20 May 2008
				Trofosfamide
ASCO2007	Not Applicable	Intraocular Lymphoma	-	Ifosfamide	(wapyeoekfe) = dwcdmynxlp ekrluwzkyh (usolrkazlc )	-	20 Jun 2007
				Trofosfamide	dezwpuzvxi(wgkvimford) = jimjjbyipc hmzbybdhxa (tttbdesiwq )
ASCO2007	Not Applicable	metastatic non-small cell lung cancer Second line	21	Weekly docetaxel + daily trofosfamide	nntjkxpwgf(ulmyvdpfwh) = fxqvobflwq ewqamtvmvd (irbjrzwiwn, 14.5 - 56.2) View more	-	20 Jun 2007