Transcript Nessun titolo diapositiva

EC917
Drug Eluting Bead: Future
Product Applications
Eva Gallardo, MD
Medical Manager, Biocompatibles UK
EC917
DEB in Glioma: Background
• Malignant Gliomas are most frequent primary brain tumours
• Total surgical resection is challenging due to infiltrative nature
• Median Survival:
• Low-grade Glioma: 5 years (most die of progression to
high-grade)
• High-Grade Glioma: <5% survival at 2 years
• Polymer drug release post-resection has improved treatment
outcomes (this therapy is under further development)
EC917
DEB in Glioma: Methods
• Study in glioblastoma rat model to evaluate efficacy of
Irinotecan and Doxorubicin Bead
• Control Group: 1-3 µL of 100-300 µm beads injected
• Dose ranging study: 1-3 µL of loaded 100-300 µm beads
injected. Histogical evaluation 12 days post-tumour implant
• Survival study: 1 µL of 100-300 µm loaded beads injected.
Animal activity and well-being assessed twice daily.
Euthanised if low scores or sudden neurological signs.
• Histological evaluation: tumour size, histomorphology, bead
location and amount, drug distribution
EC917
DEB in Glioma: Results
• No histological tissue
damage found with bland
beads
• Tumoural citotoxic effect of
both drugs with tumour
necrosis
• Neuronal, glial and
capillary cells were also
destroyed by doxorubicin
(not by irinotecan)
EC917
DEB in Glioma: Results
P Bead vs Dox Bead 0.0028
P Bead vs Iri Bead 0.0018
EC917
DEB in Glioma: Results
• DEB could be a promising new local therapy for glioma
• Doxorubin showed the longer survival but with a dose limiting
toxicity
• Further evaluation is required
EC917
DEB in Peritoneal Carcinomatosis:
Background
• Peritoneal carcinomatosis leading to malignant ascites is a
complication of several solid tumors (ovarian, gastric,
liver and pancreatic cancers)
• Appears in late disease stage – difficult to manage
• Is the life-limiting factor and leads to severe complications –
bowel obstruction
• Symptoms include severe pain and dyspnea
EC917
DEB in Peritoneal Carcinomatosis:
Methods
• Doxorubicin or Mitoxantrone loaded Beads were used in a
peritoneal colorectal carcinomatosis mice model
(a)
1 mm
(b)
1 mm
(c)
1 mm
• Control Group: direct intraperitoneal injection of unloaded
beads at 7, 10 and 12d
• Direct intraperitoneal injection of free drug or loaded Bead
(single low dose/single high dose/multiple doses)
EC917
DEB in Peritoneal Carcinomatosis:
Results
• Dox and Mitox induced dose-dependent reduction in cell
proliferation whether free or delivered by DEB
• Free drug was more effective at reducing cell viability over
time, although DEB was seen to be most effective at 72h
(slow release of the drug)
• Multiple free Dox was lethal (Dox and Mitox Bead were well
tolerated)
EC917
DEB in Peritoneal Carcinomatosis:
Results
25
20
20
Mitox DEB 100
Mitox (3)
Dox DEB 100
Dox (3)
0
Dox DEB(3)
0
Dox
5
Dox DEB
5
Mitox DEB(3)
10
Mitox
10
15
Mitox DEB
15
Control
Body Weight (g)
25
Control
Body Weight (g)
•Multiple free Mitox administration induced significant
weight decrease (Mitox Bead did not)
EC917
DEB in Peritoneal
Carcinomatosis: Results
• Multiple administration of Dox or Mitox DEB was very
efficacious in reducing tumor volume
• A single administration of Dox or Mitox DEB with 100mg/kg
dose was both well tolerated and efficacious
5
Dox DEB 100
Dox (3)
Dox DEB(3)
Dox
Dox DEB
0
20
0
Mitox DEB 100
10
40
Mitox (3)
15
60
Mitox DEB(3)
20
80
Mitox
25
Mitox DEB
30
Control
Total Tumor Volume (mm3)
100
Control
Total Tumor Volume (mm3)
35
EC917
DEB in Peritoneal
Carcinomatosis: Conclusion
• IP free drugs had efficacy against tumor cells in vivo, but
multiple applications of free drug were lethal or had significant
effect on body weight indicating poor tolerability
• Single application of high dose, or multiple application of lower
dose DEB were well tolerated and had a significant effect on
reducing tumor volume
• DEB could offer a new treatment for peritoneal carcinomatosis