Delving into the Latest Updates on Irinotecan-eluting beads with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

DEBIRI, Irinotecan bead, PARAGON Bead

+ [2]

Target

Top I

Mechanism

TOP1 inhibitors(DNA topoisomerase I inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [1]

Active Indication

Bile Duct NeoplasmsColorectal CancerGlioma+ [1]

Inactive Indication-

Originator Organization

Singapore General Hospital Pte Ltd.

Active Organization

Singapore General Hospital Pte Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC33H38N4O6

InChIKeyUWKQSNNFCGGAFS-XIFFEERXSA-N

CAS Registry97682-44-5

In order to extract the profiles of patients receiving DEBIRI treatment at best, the investigators proposed the establishment of a national prospective cohort to collect information on the greatest number of patients treated with DEBIRI. This cohort will allow a better understanding of the effectiveness, tolerance, feasibility and differences of practices at national level for this approach. These data will assist in the development of clinical trials in situations that appear to be most promising in clinical practice.

Start Date03 Feb 2016

Sponsor / Collaborator

Fédération Francophone de la Cancérologie Digestive

NCT02110953

/ TerminatedPhase 1IIT

Phase I Study of Drug-Eluting Irinotecan Beads (DEBIRI) in Refractory Metastatic Colorectal Cancer With Liver-Only or Liver-Predominant Disease

This phase I trial studies the side effects and best dose of irinotecan-eluting beads in treating patients with colon or rectal cancer that has spread to the liver and does not respond to treatment with standard therapy. Irinotecan-eluting beads are tiny beads that have been loaded with irinotecan hydrochloride, a chemotherapy drug. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. This treatment delivers the chemotherapy directly to the tumor area inside the liver instead of to the whole body as with systemic delivery of the drug. Irinotecan-eluting beads may work better that standard chemotherapy in treating patients with colon or rectal cancer that has spread to the liver.

Start Date29 Jan 2016

Sponsor / Collaborator

The Fox Chase Cancer Center

[+1]

100 Clinical Results associated with Irinotecan-eluting beads

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100 Translational Medicine associated with Irinotecan-eluting beads

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100 Patents (Medical) associated with Irinotecan-eluting beads

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108

Literatures (Medical) associated with Irinotecan-eluting beads

01 Jan 2025·JACC: Heart Failure

Natriuretic Peptides, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction

Article

Author: Mc Causland, Finnian R ; Desai, Akshay S ; Skali, Hicham ; Zile, Michael R ; Beldhuis, Iris ; Neuen, Brendon L ; McMurray, John J V ; McMurray, John JV. ; Claggett, Brian L ; Neuen, Brendon L. ; Myhre, Peder ; Mc Causland, Finnian R. ; Pfeffer, Marc A ; Vaduganathan, Muthiah ; Solomon, Scott D. ; Anand, Inder ; McGrath, Martina ; Pfeffer, Marc A. ; Claggett, Brian L. ; McMurray, John J.V. ; Solomon, Scott D ; Desai, Akshay S. ; Zile, Michael R.

BACKGROUNDN-terminal pro-B-type natriuretic peptides (NT-proBNPs) are guideline-recommended biomarkers for risk stratification in patients with heart failure. However, NT-proBNP levels are often elevated in chronic kidney disease, introducing uncertainty about their prognostic relevance in persons across a broad range of estimated glomerular filtration rate (eGFR).OBJECTIVESThe aim of this study was to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function.METHODSA pooled analysis was conducted of participants with NT-proBNP and eGFR measured at baseline in the I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction), TOPCAT (Americas region) (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function), PARAGON (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction), and DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) trials. The relationship between NT-proBNP and eGFR was assessed using piecewise linear regression. Using multivariable Cox and Poisson regression models, the association of NT-proBNP with outcomes across a range of eGFR was evaluated. The primary outcome was hospitalization for heart failure or cardiovascular death.RESULTSAmong 14,831 participants (mean age: 72.1 years; 50.3% female; mean eGFR: 63.3 mL/min/1.73 m², and median NT-proBNP: 840 pg/mL) followed up for a median 33.5 months, there were 3,092 primary outcomes. NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73 m² lower eGFR in patients with baseline eGFR ≥60, 45-<60, and <45 mL/min/1.73 m², respectively (P for nonlinearity < 0.001). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR: 1.37; 95% CI: 1.34-1.41), consistent across different eGFR categories (P for interaction = 0.42). For the same incidence of the primary outcome, NT-proBNP levels were approximately 2.5- to 3.5-fold lower in patients with eGFR <45 mL/min/1.73 m², compared with patients with eGFR ≥60 mL/min/1.73 m². Similar patterns were observed across all outcomes studied, including cardiovascular and noncardiovascular death.CONCLUSIONSThe same NT-proBNP concentration predicts a substantially higher absolute risk of adverse outcomes for people with heart failure and reduced kidney function, compared with those with preserved kidney function. These data call into question proposals for higher NT-proBNP references ranges in people with CKD, and suggest that reduced kidney function per se should not be a reason to disregard higher NT-proBNP levels.

03 Dec 2024·Circulation

Therapeutic Effects of Heart Failure Medical Therapies on Standardized Kidney Outcomes: Comprehensive Individual Participant–Level Analysis of 6 Randomized Clinical Trials

Article

Author: Neuen, Brendon L. ; Jhund, Pardeep S. ; Zannad, Faiez ; McCausland, Finnian R. ; Vaduganathan, Muthiah ; Lam, Carolyn S.P. ; Solomon, Scott D. ; Claggett, Brian L. ; Butt, Jawad H. ; Desai, Akshay S. ; Heerspink, Hiddo J.L. ; McMurray, John J.V. ; Pitt, Bertram ; Beldhuis, Iris E. ; Voors, Adriaan A. ; Packer, Milton ; Pfeffer, Marc A.

BACKGROUND:Kidney outcomes have been variably defined using nonstandardized composite end points in key heart failure trials, thus introducing complexity in their interpretation and cross-trial comparability. We examined the effects of steroidal mineralocorticoid receptor antagonists, the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan, and SGLT2 (sodium-glucose cotransporter-2) inhibitors on composite kidney end points using uniform definitions in 6 contemporary heart failure trials.METHODS:Individual participant–level data from trials of steroidal mineralocorticoid receptor antagonists (EMPHASIS-HF [Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure], TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist] Americas), angiotensin receptor-neprilysin inhibitor (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], PARAGON-HF [Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in HF With Preserved Ejection Fraction]), and SGLT2 inhibitors (DAPA-HF [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure], DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]) were included. The standardized composite kidney end point was defined as a sustained decline (a reduction in estimated glomerular filtration rate (eGFR) confirmed by a subsequent measurement at least 30 days later) in eGFR by 40%, 50%, or 57%; end-stage kidney disease; or renal death. eGFR was recalculated in a standardized manner using the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine equation.RESULTS:Among 28 690 participants across the 6 trials (median age, 69 years [interquartile range, 62–76]; 9656 [33.7%] women), the proportion experiencing the composite kidney end point with a more stringent definition of a sustained decline in kidney function (eGFR threshold of 57%) ranged from 0.3% to 3.3%. The proportion of patients experiencing this end point with a less stringent definition (eGFR threshold of 40%) ranged from 1.0% to 10.0%. The steroidal mineralocorticoid receptor antagonists doubled the risk of the composite kidney end point when applying the least stringent definition compared with placebo, but these effects were less apparent and no longer significant with application of more stringent definitions. Angiotensin receptor-neprilysin inhibitor appeared to consistently reduce the occurrence of the composite kidney end points irrespective of the specific eGFR threshold applied. The potential benefits of SGLT2 inhibitors on the composite kidney end points appeared more apparent when defined by more stringent eGFR thresholds, although none of these effects individually were statistically significant.CONCLUSIONS:When applying standardized stringent kidney end point definitions, steroidal mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitor, and SGLT2 inhibitors have either neutral or beneficial effects on kidney outcomes in heart failure. Applying less stringent definitions increased event rates but included acute declines in eGFR that might not ultimately reflect long-term effects on kidney disease progression.

01 Nov 2024·Journal of the American College of Cardiology

Systolic Blood Pressure and Pulse Pressure in Heart Failure

Article

Author: Zannad, Faiez ; Neuen, Brendon L ; McMurray, John J V ; Beldhuis, Iris E ; Anand, Inder S ; Mc Causland, Finnian R ; Pfeffer, Marc A ; Pitt, Bertram ; Claggett, Brian L ; Zile, Michael R ; Solomon, Scott D ; Vaduganathan, Muthiah ; Desai, Akshay S ; Jhund, Pardeep S ; Lu, Henri ; Kondo, Toru

BACKGROUNDHypertension is common in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), and current guidelines recommend treating systolic blood pressure (SBP) to a target <130 mm Hg. However, data supporting treatment to this target are limited. Additionally, pulse pressure (PP), a marker of aortic stiffness, has been associated with increased risk of cardiovascular events, but its prognostic impact in HFpEF has not been extensively studied.OBJECTIVESThis study aimed to explore the impact of baseline SBP and PP on cardiovascular outcomes in patients with HFmrEF or HFpEF.METHODSThe I-PRESERVE (Irbesartan in Heart Failure With Preserved Ejection Fraction), TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist)-Americas, PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in HF With Preserved Ejection Fraction), and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials were global, randomized clinical trials testing irbesartan, spironolactone, sacubitril/valsartan, and dapagliflozin, respectively, against either a placebo or an active comparator (valsartan, in PARAGON-HF), in patients with heart failure and a left ventricular ejection fraction ≥40% (in DELIVER) or ≥45% (in the other trials). The relationship between continuous baseline SBP and PP, and the primary endpoint (first heart failure hospitalization or cardiovascular death) was analyzed with restricted cubic splines. We further evaluated the prognostic impact of SBP categories (<120, 120-129, 130-139, and ≥140 mm Hg) and PP quartiles on the primary endpoint.RESULTSA total of 16,950 patients (mean age 71 ± 9 years; 49% male; mean SBP 131 ± 15 mm Hg; mean PP 55 ± 14 mm Hg) were included. The relationship between SBP and the primary endpoint was J-shaped, with the lowest risk at 120 to 130 mm Hg. A similar pattern was found for PP, with the lowest risk at 50 to 60 mm Hg. The highest SBP category (reference: 120-129 mm Hg) and PP quartile (reference: 46-54 mm Hg) were associated with a higher risk of the primary outcome (HR: 1.22; 95% CI: 1.10-1.34 and HR: 1.22; 95% CI: 1.11-1.34, respectively). Higher PP was associated with greater cardiovascular risk, regardless of SBP.CONCLUSIONSOur analysis of a large pooled dataset from 4 clinical trials, including >16,900 patients with HFmrEF/HFpEF, indicates a J-shaped relationship between both SBP and PP and cardiovascular risk. The lowest risk was observed at SBP levels between 120 and 130 mm Hg and PP values between 50 and 60 mm Hg (I-PRESERVE [Irbesartan in Heart Failure With Preserved Systolic Function], NCT00095238; TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist], NCT00094302; PARAGON-HF [Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction], NCT01920711; DELIVER [Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure], NCT03619213).

100 Deals associated with Irinotecan-eluting beads

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Bile Duct Neoplasms	-	Singapore General Hospital Pte Ltd.	-
Colorectal Cancer	-	Singapore General Hospital Pte Ltd.	-
Glioma	-	Singapore General Hospital Pte Ltd.	-
Liver Cancer	-	Singapore General Hospital Pte Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01839877 (FFCD-1201 \| FFCD 1201, CTgov)	Phase 2	colon cancer liver metastasis	58	systemic FOLFOX+DEBIRI	(zjxpnodbbo) = cwrhrhehto qjyqnmewip (xcpvwtmyyx, rkquyzfhte - wbgcxzgdkr) View more	-	08 Oct 2024
ASCO2023	Not Applicable	Colorectal Liver Metastases	101	Irinotecan-eluting HepaSphere chemoembolization plus HAIC	(sabjipaveh) = 27.7% htyngayfsx (mydfdalqqr ) View more	Positive	31 May 2023
NCT01839877 (FFCD-1201, Pubmed \| Br J Cancer)	Phase 2	Colorectal Liver Metastases First line	-	DEBIRI plus mFOLFOX6	(lporuqxzmn) = isjsgyfbqv udurkxrwob (hgxjekluxi ) View more	-	18 Aug 2020
NCT02015754 (CTgov)	Phase 2	Colorectal Liver Metastases	14	TACE+DEBIRI	fwziorpsbo(tfbtggpwmo) = lrlvyieucp rhfhfxeqtf (qqqmjhgttu, eznskmzyyh - exqhgpdwce) View more	-	22 Mar 2018
ASCO_GI2015	Phase 2	Colorectal Liver Metastases	-	DEBIRI	(ltlqrnohpw) = rjyhmagbjk dajrpapzeg (rwyvinmvro ) View more	Positive	20 Jan 2015
ASCO_GI2013	Not Applicable	Colorectal Liver Metastases Neoadjuvant	10	DEBIRI	eqnmlfhykm(qkkvevnznt) = nbbcijxowz ukkwqwmcbx (bfdavcowld ) View more	-	01 Feb 2013
ASCO_GI2012	Phase 3	Colorectal Liver Metastases	74	Polyvinyl alcohol microspheres loaded with irinotecan	gtoedlbloa(obejaucatg) = bjgwommjti swljguteym (hzhpwnqaif ) View more	Positive	01 Feb 2012
ASCO_GI2012	Phase 3	Colorectal Liver Metastases	74	Systemic chemotherapy	gtoedlbloa(obejaucatg) = ueobvkxhly swljguteym (hzhpwnqaif ) View more	Positive	01 Feb 2012
ASCO2011	Not Applicable	Lung Cancer	16	drug-eluting beads (Segmental pulmonary arterial chemoembolization (SPACE) + RFA)	nzkshcgqed(efpkrepokg) = 1 bronco-pleural fistula (5%) phaqvbezqc (eepebbmdir ) View more	-	20 May 2011
PRECISION V (ASCO2010)	Not Applicable	Hepatocellular Carcinoma	212	PRECISION TACE with drug-eluting beads (DC Beads)	(llkrizjkdz) = udzqkrklxy pcbgeixjie (cddennarfs )	-	20 May 2010
PRECISION V (ASCO2010)	Not Applicable	Hepatocellular Carcinoma	212	PRECISION TACE with drug-eluting beads (conventional transarterial chemoembolization (cTACE))	(llkrizjkdz) = kxsdmgzosm pcbgeixjie (cddennarfs )	-	20 May 2010
ASCO2010	Not Applicable	Hepatocellular Carcinoma	56	DEB-TACE with epirubicin drug-eluting beads	(aurtdvzskl) = wzkpsulitl etfcogstqd (gmtznlwclb ) View more	-	20 May 2010