Delving into the Latest Updates on Floxuridine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1-(2-Deoxy-beta-D-ribofuranosyl)-5-fluorouracil, 1-beta-D-2'-Deoxyribofuranosyl-5-flurouracil, 1beta-D-2'-Deoxyribofuranosyl-5-flurouracil

+ [18]

Target-

Mechanism-

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases+ [1]

Active Indication

Breast CancerEsophageal CarcinomaLiver Cancer+ [3]

Inactive Indication-

Originator Organization

Hospira, Inc.

Active Organization

Hanhui Pharmaceutical Co. Ltd. (China)

Inactive Organization

Hospira, Inc.

Drug Highest PhaseApproved

First Approval Date

US (18 Dec 1970),

Colorectal Cancer

Regulation-

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Structure

Molecular FormulaC9H11FN2O5

InChIKeyODKNJVUHOIMIIZ-RRKCRQDMSA-N

CAS Registry50-91-9

Patients with intrahepatic cholangiocarcinoma (IHC) have relatively aggressive tumors, and the prognosis for most of these patients is dismal. Surgery is the only option that can offer potential cure, but only an estimated 20-25 % are amenable to resection. Down-staging conventional chemotherapy has a relatively low response rate (< 50 %). Patients will be included into the respective treatment arms based on their tumour characteristics and disease stage, but also based on their ability/preferences, as HAI-FUDR/DEX requires going to Oslo every fortnight for the duration of the treatment and SIRT has some limitations regarding tumour distribution.
Data from the MSKCC has suggested a clinically relevant benefit from adding intrahepatic chemotherapy to systemic therapy. HAI-FUDR/DEX is not approved in Norway and can only be evaluated in a protocolized trial. Given the risk of distant disease progression with IHC, the addition of conventional systemic chemotherapy makes good clinical sense, and data from MSKCC supports this approach. SIRT is another modality also applied trans-arterially and directly into the tumour. This treatment is approved in Norway and available in Bergen and in Oslo. It is far less cumbersome to deliver and maintain than HAI-FUDR/DEX. The efficacy and safety of the two treatment groups, HAI-FUDR/DEX and SIRT, will be compared in a parallel cohort (non-randomized) design

Start Date13 Feb 2024

Sponsor / Collaborator

Oslo universitetssykehus HF

NCT05863195 / RecruitingPhase 3IIT

A Randomized Phase III Study of Systemic Therapy With or Without Hepatic Arterial Infusion for Unresectable Colorectal Liver Metastases: The PUMP Trial

This phase III trial compares hepatic arterial infusion (HAI) (pump chemotherapy) in addition to standard of care chemotherapy versus standard of care chemotherapy alone in treating patients with colorectal cancer that has spread to the liver (liver metastases) and cannot be removed by surgery (unresectable). HAI uses a catheter to carry a tumor-killing chemotherapy drug called floxuridine directly into the liver. HAI is already approved by the Food and Drug Administration (FDA) for use in metastatic colorectal cancer to the liver, but it is only available at a small number of hospitals, and most of the time it is not used until standard chemotherapy stops working. Standard chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding HAI to standard chemotherapy may be effective in shrinking or stabilizing unresectable colorectal liver metastases.

Start Date19 Oct 2023

Sponsor / Collaborator

ECOG-ACRIN Medical Research Foundation, Inc.

[+1]

NCT05286814 / RecruitingPhase 2IIT

Phase II Study Evaluating the Efficacy of M9241 in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer or Intrahepatic Cholangiocarcinoma

Background:
One way to treat liver cancer is to deliver chemotherapy drugs only to the liver (and not to the whole body). Researchers want to see if adding the drug M9241 can improve the treatment. The drug triggers the immune system to fight cancer.
Objective:
To see if treatment with HAIPs to deliver liver-directed chemotherapy in combination with M9241 is effective for certain cancers.
Eligibility:
People aged 18 and older who have cancer of the bile ducts that is only in the liver, or colorectal cancer that has spread to the liver.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood tests
Pregnancy test (if needed)
Tumor biopsy (if needed)
Electrocardiogram
Computed tomography (CT) scans
Participants will have an abdominal operation. A catheter will be placed into an artery that feeds blood to the liver. The catheter will then be attached to the HAIP. The HAIP will lay under the skin on the left side of the abdomen.
Participants will have chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. M9241 will be injected under the skin every 4 weeks. They will get systemic chemotherapy through an IV or mediport every 2 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects.
Participants will have 2 study visits each month. They will have CT scans every 8 weeks. At visits, they will repeat some screening tests.
Participants will have a follow-up visit 1 month after treatment ends. Then they will be contacted every 6 months for 5 years.

Start Date24 Oct 2022

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Floxuridine

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100 Translational Medicine associated with Floxuridine

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100 Patents (Medical) associated with Floxuridine

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2,128

Literatures (Medical) associated with Floxuridine

01 Dec 2024·Neoplasia

ARID1A loss sensitizes colorectal cancer cells to floxuridine

Article

Author: He, Yilin ; Wang, Kejin ; Han, Zelong ; Liu, Side ; Zhang, Xu ; Xiang, Cheng ; Lu, Jingyi ; Peng, Wenxuan ; Wang, Zhen ; Wang, Zihuan ; Yu, Yingnan ; Wu, Changjie ; Pan, Lei ; Song, Yijiang

The loss-of-function mutation of AT-rich interactive domain 1A (ARID1A) frequently occurs in various types of cancer, making it a promising therapeutic target. In the present study, we performed a screening of an FDA-approved drug library in ARID1A isogenic colorectal cancer (CRC) cells and discovered that ARID1A loss sensitizes CRC cells to floxuridine (FUDR), an antineoplastic agent used for treating hepatic metastases from CRC, both in vivo and in vitro. As a pyrimidine analogue, FUDR induces DNA damage by inhibiting thymidylate synthase (TS) activity. ARID1A, as a regulator of DNA damage repair, when lost, exacerbates FUDR-induced DNA damage, leading to increased cell apoptosis. Specifically, ARID1A deficiency impairs DNA damage repair by downregulating Chk2 phosphorylation, thereby sensitizing cancer cells to FUDR. Notably, we found that FUDR exhibited increased sensitivity in ARID1A-deficient cells compared to 5-fluorouracil (5-FU), a commonly used anticancer drug for CRC. This suggests that FUDR is superior to 5-FU in treating ARID1A-deficient CRC. In conclusion, ARID1A loss significantly heightens sensitivity to FUDR by promoting FUDR-induced DNA damage in CRC. These findings offer a novel therapeutic approach for the treatment of CRC characterized by ARID1A loss-of-function mutations.

01 Dec 2024·Virology

5-Bromo-2′-deoxyuridine inhibits African swine fever virus (ASFV) replication via interfering viral DNA replication and suppressing the formation of viral factories

Article

Author: Chen, Jianxin ; Ou, Weixin ; Luo, Ding ; Lin, Qisheng ; Long, Feixiang ; Liu, Jinyi ; Long, Feixaing ; Su, Guanming ; Liu, Zexin ; Su, Guangmin ; Su, Guoming

African swine fever (ASF), caused by ASF virus (ASFV), represents one of the most economically important viral infectious diseases in swine industry worldwide. So far there is no vaccine or antiviral drug for controlling ASF pandemics. In the present study, we assessed inhibition of six nucleoside analogues against ASFV replication in ex vivo primary porcine alveolar macrophages (PAMs), including the first approved antiviral drug idoxuridine. Our results showed that, out of the assessed six compounds, 5-Bromo-2'-Deoxyuridine (5-BrdU, an analog of idoxuridine), exhibited the strongest inhibition on the replication of ASFV in PAMs with a 50% inhibitory concentration (IC₅₀) value of 2.9 μM and a low cytotoxicity (CC₅₀ > 270 μM). Moreover, we showed that 5-BrdU interferes with ASFV DNA replication by incorporating into viral replicating DNA molecules as a competitive substrate for deoxythymidine, ultimately inhibiting the formation of ASFV viral factories. Altogether, our findings suggest that 5-BrdU could serve as a promising therapeutic agent for combating ASFV infection.

04 Nov 2024·Molecular Pharmaceutics

RNA Nanotechnology for Codelivering High-Payload Nucleoside Analogs to Cancer with a Synergetic Effect

Article

Author: Lee, Wen-Jui ; Li, Xin ; Ho, Yuan-Soon ; Jin, Kai ; Cheng, Tzu-chun ; Liao, You-Cheng ; Guo, Peixuan ; Chen, Li-Ching

Nucleoside analogs are potent inhibitors for cancer treatment, but the main obstacles to their application in humans are their toxicity, nonspecificity, and lack of targeted delivery tools. Here, we report the use of RNA four-way junctions (4WJs) to deliver two nucleoside analogs, floxuridine (FUDR) and gemcitabine (GEM), with high payloads through routine and simple solid-state RNA synthesis and nanoparticle assembly. The design of RNA nanotechnology for the co-delivery of nucleoside analogs and the chemotherapeutic drug paclitaxel (PTX) resulted in synergistic effects and high efficacy in the treatment of Triple-Negative Breast Cancer (TNBC). The 4WJ-drug complexes were confirmed to have efficient tumor spontaneous targeting and no toxicity because the motility of RNA nanoparticles has been previously shown to enable these RNA-drug complexes to spontaneously accumulate in tumor blood vessels. The negative charge of RNA enables those RNA complexes that are not targeted to tumor vasculature to circulate in the blood and enter the urine through the kidney glomerulus, without accumulating in organs, therefore being nontoxic. Drug incorporation into RNA 4WJ can be precisely controlled with a defined loading amount, location, and ratio. The incorporation of nucleoside analogs into 4WJ only requires one step using nucleoside analogue phosphoramidites during solid-phase RNA synthesis, without the need for additional conjugation and purification processes.

100 Deals associated with Floxuridine

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External Link

KEGG	Wiki	ATC	Drug Bank
D04197	Floxuridine	L01BC09	DB00322

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Breast Cancer	CN	Hanhui Pharmaceutical Co. Ltd. (China)	01 Jan 2001
Esophageal Carcinoma	CN	Hanhui Pharmaceutical Co. Ltd. (China)	01 Jan 2001
Liver Cancer	CN	Hanhui Pharmaceutical Co. Ltd. (China)	01 Jan 2001
Lung Cancer	CN	Hanhui Pharmaceutical Co. Ltd. (China)	01 Jan 2001
Rectal Cancer	CN	Hanhui Pharmaceutical Co. Ltd. (China)	01 Jan 2001
Stomach Cancer	CN	Hanhui Pharmaceutical Co. Ltd. (China)	01 Jan 2001

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04251715 (HELIX-1, ASCO_GI2024) Manual	Phase 2	Unresectable Intrahepatic Cholangiocarcinoma First line	5	mFOLFIRINOX + floxuridine+mFOLFIRI	(ewltjkuior) = iyjpffdfir mgscdumqub (tcmtqldtnz ) View more	Positive	18 Jan 2024
NCT00645710 (CTgov)	Phase 1/2	Recurrent Colon Cancer \| Rectal Cancer \| Liver metastases \| Colorectal Liver Metastases \| Metastatic Colorectal Carcinoma	16	1- FUdR (Dose Level 1- FUdR 0.10 mg/kg/Day)	bjobhbspaq(kieakokpgc) = tmualevrfk ssfwwfxigl (kicrstbzcq, ankcdipdcz - qdjtkxvxmt) View more	-	28 Mar 2019
NCT00645710 (CTgov)	Phase 1/2		16	2 - FUdR (Dose Level 2 - FUdR 0.15 mg/kg/Day)	bjobhbspaq(kieakokpgc) = ueqeeuhqej ssfwwfxigl (kicrstbzcq, oujyxjikgs - jodntyszax) View more	-	28 Mar 2019
PHOENIX-GC (ASCO_GI2019)	Phase 3	Peritoneal Neoplasms \| Stomach Cancer	-	Surgery + IP floxuridine/leucovorin CTX	(adgekfhkhr) = tttxgnydjk xcduhmzoqe (jgacgvsmzp ) View more	-	29 Jan 2019
PHOENIX-GC (ASCO_GI2019)	Phase 3	Peritoneal Neoplasms \| Stomach Cancer	-	CTX alone	(adgekfhkhr) = psaybbnxlv xcduhmzoqe (jgacgvsmzp ) View more	-	29 Jan 2019
NCT01692704 (ASCO_GI2018)	Phase 1/2	Unresectable Intrahepatic Cholangiocarcinoma	12	Systemic intravenous gemcitabine + cisplatin + hepatic arterial infusion with floxuridine	(nyuuzfkrno) = uahyuxjwqa phjcemsqvc (puhunichxa ) View more	-	26 Feb 2018
NCT00587067 (CTgov)	Phase 2	Unresectable Hepatocellular Carcinoma	34	Floxuridine+Dexamethasone	cnswtdiyri(dxggsthvvm) = njozdsuqmt jtlypageje (asfujjunqt, uqnzlkpyox - mehdwbofoo) View more	-	04 Aug 2017
NCT00002842 (CTgov)	Phase 2	Neoplasm Metastasis \| Colorectal Liver Metastases \| Metastatic Colorectal Carcinoma	49	adjuvant therapy+Leucovorin Calcium+floxuridine+fluorouracil	lrbeezxkxs(sdqtaaurjo) = ekexzydcgn bpakwppces (kxjwqzwxse, mgpejobscr - hxwrogqpwl) View more	-	11 Apr 2017
AACR2016	Phase 1	Liver Cancer Second line	-	TBI 302	jzacjrknco(xscovnycly) = yebjwxzwvp cdnccmuiyx (kpzjwjsxce )	-	15 Jul 2016
AACR2016	Phase 1	Liver Cancer Second line	-	Saline	jzacjrknco(xscovnycly) = jnzfzvqdne cdnccmuiyx (kpzjwjsxce )	-	15 Jul 2016
NCT00448760 (ASCO_GI2016)	Phase 2	Locally Advanced Gastroesophageal Junction Adenocarcinoma Neoadjuvant \| Adjuvant	29	Floxuridine, Leucovorin, Oxaliplatin,Floxuridine, Leucovorin, Oxaliplatin,Floxuridine, Leucovorin, Oxaliplatin, and Docetaxel (FLOD)	(rmlfmipcff) = gjovivkqkh onoanlosgh (vdyokrkysd ) View more	Positive	01 Feb 2016
NCT00448682 (CTgov)	Phase 2	Metastatic gastric adenocarcinoma	25	Leucovorin+Docetaxel+FUdR+Oxaliplatin	kdssvryxex(ckmgkzgeye) = orznzxeenf chukalwqke (ubcbkhlwdw, oilbrchfdg - kigjtyujwr) View more	-	13 May 2013
NCT00449163 (CTgov)	Phase 2	Metastatic Colorectal Carcinoma	25	Leucovorin+Floxuridine+Bevacizumab+Irinotecan	wcrudxxgkn(veellqizfu) = satypghaws saantnlwcn (texhfwaftt, wqjusxcqnk - ravmhgwczw) View more	-	28 Feb 2013