Delving into the Latest Updates on Trofosfamide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

A-4828, NSC-109723, Z-4828

+ [1]

Target

DNA

Mechanism

DNA inhibitors(DNA inhibitors), DNA alkylating agents

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization-

Active Organization-

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure

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]

EUCTR2011-002611-29-DE / Not yet recruitingPhase 1/2IIT

A prospective phase I and consecutive phase II, twoarm,randomized multi-center trial of temsirolimus incombination with pioglitazone, etoricoxib andmetronomic low-dose trofosfamide versus dacarbazine(DTIC) in patients with advanced melanoma

Start Date04 Apr 2012

Sponsor / Collaborator-

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]

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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130

Literatures (Medical) associated with Trofosfamide

23 Jan 2024·Zhonghua zhong liu za zhi [Chinese journal of oncology]

[Progress in the treatment of soft tissue sarcoma in the 2023 annual meeting of the American Society of Clinical Oncology].

Article

Author: Liu, W F ; Zhao, J L

Soft tissue sarcoma (STS) is a group of rare malignant tumors originating from mesenchymal tissue, with a high degree of malignancy and a wide range of pathological subtypes. The prognosis varies among different subtypes, and treatment increasingly relies on selecting appropriate treatment methods for different subtypes. Surgical treatment is still the main treatment method at present, and the development of immune and targeted therapy also brings new hope for the treatment of soft tissue sarcoma. Immune checkpoint inhibitors, oncolytic viruses and T cell therapy have shown well safety and efficacy in clinical trials. Targeted drugs such as trabectedin and lenvatinib have changed the treatment pattern of soft tissue sarcoma. Currently, chemotherapy based on doxorubicin and ifosfamide is still the first line treatment for patients with advanced soft tissue sarcoma who have distant metastasis. However, the adverse reactions of doxorubicin limit its application in elderly patients, and trofosfamide has shown good efficacy and safety as an alternative in clinical trials. The efficacy of postoperative radiotherapy has been confirmed, which can reduce the local recurrence rate after surgical resection of soft tissue sarcoma. In summary, multimodal comprehensive treatment has become the main strategy for the treatment of soft tissue sarcoma. The combination of different treatment methods can generate synergistic effects and help patients obtain more clinical benefits, such as the combination of doxorubicin and immune checkpoint inhibitors, and the combination of antiangiogenic drugs and chemotherapy drugs. At the 2023 annual meeting of the American Society of Clinical Oncology (ASCO), oncologists from all over the world reported many researches related to the treatment of soft tissue sarcoma. This article aims to review the new progress in the treatment of soft tissue sarcoma in the 2023 annual meeting of ASCO.

01 Jan 2024·Pediatric blood & cancer

Significance of fusion status, Oberlin risk factors, local and maintenance treatment in pediatric and adolescent patients with metastatic rhabdomyosarcoma: Data of the European Soft Tissue Sarcoma Registry SoTiSaR

Article

Author: Sparber-Sauer, Monika ; Heinz, Amadeus T ; Fuchs, Jörg ; von Kalle, Thekla ; Seitz, Guido ; Vokuhl, Christian ; Klingebiel, Thomas ; Ljungman, Gustaf ; Münter, Marc ; Pajtler, Kristian W ; Stegmaier, Sabine ; Schönstein, Anton ; Timmermann, Beate ; Ebinger, Martin ; Juntti, Hanna ; Kratz, Christian P ; Koscielniak, Ewa

Abstract:

Background:

Outcome of primary metastatic rhabdomyosarcoma (RMS) is poor. Certain risk factors as fusion status, Oberlin score, and local treatment of primary tumor are known to influence prognosis.

Procedure:

Patients with metastatic RMS were treated according to Cooperative Weichteilsarkom Studiengruppe (CWS) guidance with chemotherapy (CHT), radiotherapy (RT) excluding total lung irradiation (TLI), complete resection of the primary tumor, and metastasectomy if possible. Kaplan–Meier estimators and Cox proportional hazard models were used to examine event‐free survival (EFS) and overall survival (OS) involving also landmark analyses.

Results:

In the European Soft Tissue Sarcoma Registry SoTiSaR (2009–2018), 211 patients were analyzed. Many patients had fusion‐positive alveolar RMS (n = 83; 39%). Median age was 9.4 years [0.1–19.7 years]. Treatment primarily consisted of CHT with CEVAIE (carboplatin, epirubicine, vincristine, actinomycin‐D, ifosfamide, etoposide: 86%, other regimens: 14%), RT (71%), resection of primary tumor (37%), metastasectomy (19%), and lymph node sampling/dissection (21%). Maintenance treatment (MT) (oral trofosfamide, idarubicin, etoposide) was added in 74% of patients. Oberlin factors, fusion status, and MT were predictive for EFS and OS. MT with O‐TIE was not improving outcome when adjusting for the immortal time bias. Local treatment of the primary tumor and radical irradiation (except TLI) improved EFS, not OS, when adjusting for the Oberlin score. Patients with fusion‐negative alveolar RMS (n = 9) had an excellent outcome with a 5‐year EFS and OS of 100%, compared to patients with embryonal RMS (49%/62%), PAX7‐ (22%/47%) and PAX3/FOXO1‐positive ARMS (10/13%), respectively (p < .001).

Conclusions:

Prognosis of metastatic RMS primarily depends on fusion status and Oberlin score. Fusion status needs to be considered in future trials to optimize treatment outcome. The role of radical irradiation needs further investigation.

01 Feb 2023·Journal of neuro-oncology

How I treat recurrent pediatric high-grade glioma (pHGG): a Europe-wide survey study

Article

Author: Benesch, Martin ; Giese, Barbara ; van Buiren, Miriam ; Perwein, Thomas ; Nussbaumer, Gunther ; von Bueren, André O ; Kramm, Christof Maria

Abstract:

Purpose:

As there is no standard of care treatment for recurrent/progressing pediatric high-grade gliomas (pHGG), we aimed to gain an overview of different treatment strategies.

Methods:

In a web-based questionnaire, members of the SIOPE-BTG and the GPOH were surveyed on therapeutic options in four case scenarios (children/adolescents with recurrent/progressing HGG).

Results:

139 clinicians with experience in pediatric neuro-oncology from 22 European countries participated in the survey. Most respondents preferred further oncological treatment in three out of four cases and chose palliative care in one case with marked symptoms. Depending on the case, 8–92% would initiate a re-resection (preferably hemispheric pHGG), combined with molecular diagnostics. Throughout all case scenarios, 55–77% recommended (re-)irradiation, preferably local radiotherapy > 20 Gy. Most respondents would participate in clinical trials and use targeted therapy (79–99%), depending on molecular genetic findings (BRAF alterations: BRAF/MEK inhibitor, 64–88%; EGFR overexpression: anti-EGFR treatment, 46%; CDKN2A deletion: CDK inhibitor, 18%; SMARCB1 deletion: EZH2 inhibitor, 12%). 31–72% would administer chemotherapy (CCNU, 17%; PCV, 8%; temozolomide, 19%; oral etoposide/trofosfamide, 8%), and 20–69% proposed immunotherapy (checkpoint inhibitors, 30%; tumor vaccines, 16%). Depending on the individual case, respondents would also include bevacizumab (6–18%), HDAC inhibitors (4–15%), tumor-treating fields (1–26%), and intraventricular chemotherapy (4–24%).

Conclusion:

In each case, experts would combine conventional multimodal treatment concepts, including re-irradiation, with targeted therapy based on molecular genetic findings. International cooperative trials combining a (chemo-)therapy backbone with targeted therapy approaches for defined subgroups may help to gain valid clinical data and improve treatment in pediatric patients with recurrent/progressing HGG.

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

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CWS-2007HR (ASCO2022) Manual	Phase 3	Neoplasms \| Rhabdomyosarcoma	195	trofosfamide+etoposide+idarubicine+trofosfamide	hudgdgbyxs(hkhjtdoyvg) = Toxicity grade 3 (no grade 4) in the M-arm was: hematological in 51 %, febrile infection 5%, sensory neuropathy in 1% pts sajqmhjqlk (bxnxxcjycz ) View more	Negative	02 Jun 2022
				vincristine+actinomycin D+doxorubicin+ifosfamide
NCT00204568 (Pubmed) Manual	Phase 2	Metastatic Soft Tissue Sarcoma First line	120	trofosfamide	eiyyooinfm(vlyfytndqr) = bjwqlthpad qxfoevhxpq (bonnytzlbv, 18.0 ~ 39.1) View more	Positive	01 Jan 2020
				Doxorubicin	eiyyooinfm(vlyfytndqr) = ewszrgdbsg qxfoevhxpq (bonnytzlbv, 21.2 ~ 52.8) View more
NCT00204568 (ASCO2018)	Phase 2	Metastatic Soft Tissue Sarcoma First line	-	Trofosfamide	xsxibfybjp(bjpyazajpz) = gqnxbghchl vjfjbvemkb (guofnqjepe, 1.6 - 20.9) View more	Positive	01 Jun 2018
				Adriamycin	xsxibfybjp(bjpyazajpz) = lcwyzrdevp vjfjbvemkb (guofnqjepe, 2.2 - 14.9%) View more
ERS2013	Not Applicable	Advanced Lung Non-Small Cell Carcinoma	-	Trofosfamide	vttsfivdfm(dtlutefjmy) = bkdcbytqos lvuzkrpnzg (oujoaegglg, 9.96 - 18.04) View more	Positive	01 Sep 2013
ASCO2008	Not Applicable	Intraocular Lymphoma	10	Ifosfamide	hdcvjopnfm(hwfvzpuqvx) = Acute toxicity was mainly hematologic rkcbgqcjzn (lpfddawgel ) View more	-	20 May 2008
				Trofosfamide
ASCO2007	Not Applicable	metastatic non-small cell lung cancer Second line	21	Weekly docetaxel + daily trofosfamide	hlqngklpxb(ouvwecfcye) = icpqyulmfh vjdvyormkg (aiqexhvoxs, 14.5 - 56.2) View more	-	20 Jun 2007
ASCO2007	Not Applicable	Intraocular Lymphoma	-	Ifosfamide	liupfdncfr(omfteikjqd) = blohrslude yfzrcdhsgu (vmwjpzuxav )	-	20 Jun 2007
				Trofosfamide	awneaorqbc(nwbweasdyc) = myczaysiqf rvqjipptnl (pmhmycnvwg )