A prospective study of irinotecan drug-eluting beads (DEBIRI) combined with FOLFIRI in patients after failure of FOLFOX with colorectal liver metastases
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2679864 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Background
Hepatic metastases of colorectal cancer (MCC) is quite common and is a major source of morbidity and mortality. There has been evidence to show that hepatic arterial chemoembolisation using DC beads (drug eluting beads, 100-300μm) loaded with irinotecan (DEBIRI) showed improved overall survival when compared to systemic therapy (FOLFIRI), but being larger they have their limitations.
New 70-150μm beads are recently available and currently there is limited data concerning its use. Safety of these beads have not been tested in local patients.
Hypothesis / Aim To study the safety and pharmacokinetics of the smaller 70-150μm DEBIRI in a pilot study of 5 patients. The smaller 70-150μm beads will be able to deliver a more consistent and higher dose to tumoral tissue with a smaller systemic dose. Being smaller and less embolic, it will also be better tolerated. Patients will also be genotyped for their UGT1A1*28 and UGT1A1*6 polymorphism status as the latter genotypes are associated with decreased clearance of irinotecan and SN-38 in Asian patients.
Methods Single centre, pilot study, prospectively recruiting 5 patients with unilobar disease, refractory to systemic chemotherapy
The primary endpoints:
1. establish safety and toxicity profile of the irinotecan loaded DEBIRI beads
2. establish pharmacokinetics and systemic exposure of irinotecan and its active metabolite, SN-38.
The secondary outcome measurements:
1. the incidence and severity of adverse events, liver function parameters and laboratory abnormalities;
2. response rate,
3. progression free survival
4. overall survival
Clinical Significance
This treatment modality has the advantage of directly delivering irinotecan to the liver metastases from colorectal cancer. This local mode of drug delivery may result in a higher intratumoral drug concentration and rapid tumour shrinkage leading to downstaging of the hepatic metastatic lesions. These therapeutic outcomes may also downstage patients to hepatic resection.
| 2182836 | ecrin-mdr-crc
Project description:PurposeTo develop a simple method to produce radiopaque drug-eluting microspheres (drug-eluting beads [DEBs]) that could be incorporated into the current clinical transcatheter arterial chemoembolization workflow and evaluate their performance in vitro and in vivo.Materials and methodsAn ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and ethanol solution was added to a lyophilized 100-300 µm bead before loading with doxorubicin. These radiopaque drug-eluting beads (DEBs; Biocompatibles UK Ltd, Farnham, United Kingdom) were evaluated in vitro for x-ray attenuation, composition, size, drug loading and elution, and correlation between attenuation and doxorubicin concentration. In vivo conspicuity was evaluated in a VX2 tumor model.ResultsLipiodol was loaded into lyophilized beads using two glass syringes and a three-way stopcock. Maximum bead attenuation was achieved within 30 minutes. X-ray attenuation of radiopaque beads increased linearly (21-867 HU) with the amount of beads (0.4-12.5 vol%; R(2) = 0.9989). Doxorubicin loading efficiency and total amount eluted were similar to DC Bead (Biocompatibles UK Ltd); however, the elution rate was slower for radiopaque DEBs (P < .05). Doxorubicin concentration linearly correlated with x-ray attenuation of radiopaque DEBs (R(2) = 0. 99). Radiopaque DEBs were seen in tumor feeding arteries after administration by fluoroscopy, computed tomography, and micro-computed tomography, and their location was confirmed by histology.ConclusionsA simple, rapid method to produce radiopaque DEBs was developed. These radiopaque DEBs provided sufficient conspicuity to be visualized with x-ray imaging techniques.
| S-EPMC6663477 | biostudies-literature
Project description:Chemoembolization with drug-eluting beads is a type of locoregional therapy currently being used for the treatment of hepatocellular carcinoma and metastatic disease to the liver. This treatment has proven effectiveness in controlling tumor growth, extending survival time, and improving quality of life. Chemoembolization with drug-eluting beads have been shown to be safe, but like any other invasive procedure, can have associated complications. The authors present a case of intrahepatic biloma formation occurring as a result of treatment with drug-eluting beads.
| S-EPMC3193327 | biostudies-other
Project description:This is a multicentre, open labeled, single arm study to determine effectiveness and safety of chemoembolization with Irinotecan-Eluting Bead(DEBIRI) in the treatment of unresectable liver metastases in patients with colorectal cancer after chemotherapy failure.
| 2246057 | ecrin-mdr-crc
Project description:Transarterial chemoembolization has proven benefit in the treatment of unresectable hepatocellular carcinoma (HCC). Commonly reported symptoms following chemoembolization with or without drug-eluting beads include abdominal pain, nausea, and low-grade fever, which typically limited resolve within a few days. A recent study comparing traditional chemoembolization versus chemoembolization with drug-eluting beads demonstrated similar survival between the two techniques, but improved tolerability when the drug-eluting beads were used. This case report describes a patient with unresectable HCC undergoing chemoembolization with drug-eluting beads. The postprocedure course was complicated by interstitial pneumonitis secondary to shunting of the drug-eluting beads containing doxorubicin to both lungs via tumor vasculature. This case highlights the relationship between the number and size of the tumors to be treated, arteriovenous shunting within the liver/tumors, and the size of the embolization particles.
| S-EPMC3193323 | biostudies-other
Project description:Nontarget embolization is a relatively common cause of post-chemoembolization complications. Clinical presentation following nontarget embolization varies from minimal to fatal, and oftentimes relates to the vascular distribution embolized rather than the amount or type of embolic agent. Post-chemoembolization pancreatitis is an uncommon complication, but one that is known to occur. The following manuscript presents a case of post-chemoembolization pancreatitis, and suggests methods to decrease this complication as well as treatment once the complication occurs.
| S-EPMC4346048 | biostudies-other
Project description:PURPOSE:To determine local doxorubicin levels surrounding radiopaque drug-eluting beads (DEBs) in normal swine liver and kidney following transcatheter arterial chemoembolization. The influence of bead size (70-150 ?m or 100-300 ?m) was compared with regard to tissue penetration and spatial distribution of the bead, as well as eventual drug coverage (ie, amount of tissue exposed to drug). MATERIALS AND METHODS:Radiopaque DEBs were synthesized by suspension polymerization followed by incorporation of iodized oil and doxorubicin. Chemoembolization of swine liver and kidney was performed under fluoroscopic guidance. Three-dimensional tissue penetration of "imageable" DEBs was investigated ex vivo with micro-computed tomography (microCT). Drug penetration from the bead surface and drug coverage was evaluated with epifluorescence microscopy, and cellular localization of doxorubicin was evaluated with confocal microscopy. Necrosis was evaluated with hematoxylin and eosin staining. RESULTS:MicroCT demonstrated that 70-150-?m DEBs were present in more distal arteries and located in a more frequent and homogeneous spatial distribution. Tissue penetration of doxorubicin from the bead appeared similar (?300 ?m) for both DEBs, with a maximum tissue drug concentration at 1 hour coinciding with nuclear localization of doxorubicin. The greater spatial frequency of the 70-150-?m DEBs resulted in approximately twofold improved drug coverage in kidney. Cellular death is predominantly observed around the DEBs beginning at 8 hours, but increased at 24 and 168 hours. CONCLUSIONS:Smaller DEBs penetrated further into targeted tissue (ie, macroscopic) with a higher spatial density, resulting in greater and more uniform drug coverage (ie, microscopic) in swine.
| S-EPMC3360470 | biostudies-literature
Project description:Interventions: Hepatic Arterial Chemoembolization using drug-eluting beads loaded with irinotecan (DEBIRI) for Refractory Colorectal Cancer with Liver Metastases.;Colorectal cancer, Liver metastasis, DEBIRI
Primary outcome(s): liver-specific progression-free survival
Study Design: single arm study, open(masking not used), uncontrolled control, single assignment, treatment purpose
| 2615389 | ecrin-mdr-crc
Project description:Purpose:
The purpose of this study is to determine the feasibility and safety of using small beads (70-150 micron in place of 100-300 micron) to deliver chemotherapy into the liver to treat patients with liver lesions from colorectal cancer. The beads (LC-Bead M1) will be loaded with irinotecan (DEBIRI-M1), and used to administer transarterial chemoembolization (TACE).
Eligibility:
Patients with liver cancer from colorectal cancer.
Study Overview/ Treatment:
DEBIRI, loaded with irinotecan, is a device that utilizes tiny beads (70-150 microns) to deliver chemotherapy agents into liver tumor(s) via the hepatic artery. This device allows for continuous release of irinotecan into the liver tumor tissue(s) causing necrosis of the targeted tumor(s). The potential advantages of the smaller beads are deeper penetration into the tumor bed, while avoiding premature proximal occlusion of vessels feeding the tumor, and more consistent dosing. Response to therapy will be evaluated monthly by clinic visits and blood tests (to include assessment of liver function and tumor markers) and by imaging (usually MRIs) every 1-2 months. Patients will be on study for 6 months after which they will be exited from the study and followed for survival. Once exited from the study they will continue to be eligible to receive DEBIRI, should it be recommended.
| 2157209 | ecrin-mdr-crc
Project description:OBJECTIVES:Our study sought to compare the overall survival in patients with hepatocellular carcinoma (HCC) and portal venous thrombosis (PVT), treated with either conventional trans-arterial chemoembolization (cTACE) or drug-eluting beads (DEB) TACE. METHODS:This retrospective analysis included a total of 133 patients, treated without cross-over and compared head-to-head by means or propensity score weighting. Mortality was compared using survival analysis upon propensity score weighting. Adverse events and liver toxicity grade ?3 were recorded and reported for each TACE. In order to compare with historical sorafenib studies, a sub-group analysis was performed and included patients who fulfilled the SHARP inclusion criteria. RESULTS:The median overall survival (MOS) of the entire cohort was 4.53 months (95 % CI, 3.63-6.03). MOS was similar across treatment arms, no significant difference between cTACE (N?=?95) and DEB-TACE (N?=?38) was observed (MOS of 5.0 vs. 3.33 months, respectively; p?=?0.157). The most common adverse events after cTACE and DEB- TACE, respectively, were as follows: post-embolization syndrome [N?=?57 (30.0 %) and N?=?38 (61.3 %)], diarrhea [N?=?3 (1.6 %) and N?=?3 (4.8 %)], and encephalopathy [N?=?11 (5.8 %) and N?=?2 (3.2 %)]. CONCLUSION:Our retrospective study could not reveal a difference in toxicity and efficiency between cTACE and DEB-TACE for treatment of advanced stage HCC with PVT. KEY POINTS:• Conventional TACE (cTACE) and drug-eluting-beads TACE (DEB-TACE) demonstrated equal safety profiles. • Survival rates after TACE are similar to patients treated with sorafenib. • Child-Pugh class and tumor burden are reliable predictors of survival.
| S-EPMC5470590 | biostudies-literature