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EC917
Eva Gallardo, MDMedical Manager, Biocompatibles UK
Drug Eluting Bead: Future Product Applications
EC917
• 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)
DEB in Glioma: Background
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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
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• 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)
DEB in Glioma: Results
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DEB in Glioma: Results
P Bead vs Dox Bead 0.0028
P Bead vs Iri Bead 0.0018
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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
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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
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DEB in Peritoneal Carcinomatosis: Methods
• Doxorubicin or Mitoxantrone loaded Beads were used in a peritoneal colorectal carcinomatosis mice model
• 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)
(a) (b) (c)1 mm 1 mm 1 mm(a) (b) (c)1 mm 1 mm 1 mm
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• 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)
DEB in Peritoneal Carcinomatosis: Results
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DEB in Peritoneal Carcinomatosis: Results
Bod
y W
eigh
t (g
)
Bod
y W
eigh
t (g
)
25
20
15
10
5
0
25
20
15
10
5
0
Co
ntr
ol
Do
xD
EB
Do
x
Do
xD
EB
(3)
Do
x(3
)
Do
xD
EB
10
0
Co
ntr
ol
Mito
xD
EB
Mito
x
Mito
xD
EB
(3)
Mito
x(3
)
Mito
xD
EB
10
0
Bod
y W
eigh
t (g
)
Bod
y W
eigh
t (g
)
25
20
15
10
5
0
25
20
15
10
5
0
25
20
15
10
5
0
25
20
15
10
5
0
Co
ntr
ol
Do
xD
EB
Do
x
Do
xD
EB
(3)
Do
x(3
)
Do
xD
EB
10
0
Co
ntr
ol
Mito
xD
EB
Mito
x
Mito
xD
EB
(3)
Mito
x(3
)
Mito
xD
EB
10
0
•Multiple free Mitox administration induced significant weight decrease (Mitox Bead did not)
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• 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
To
tal T
umo
rV
olum
e (
mm
3 )
To
tal T
umo
rV
olum
e (
mm
3 )
35
30
25
15
5
0
20
10
100
80
60
40
20
0
Con
tro
l
Dox
DE
B
Dox
Dox
DE
B(3
)
Dox
(3)
Dox
DE
B 1
00
Con
tro
l
Mito
xD
EB
Mito
x
Mito
xD
EB
(3)
Mito
x(3
)
Mito
xD
EB
100
To
tal T
umo
rV
olum
e (
mm
3 )
To
tal T
umo
rV
olum
e (
mm
3 )
35
30
25
15
5
0
20
10
35
30
25
15
5
0
20
10
100
80
60
40
20
0
100
80
60
40
20
0
Con
tro
l
Dox
DE
B
Dox
Dox
DE
B(3
)
Dox
(3)
Dox
DE
B 1
00
Con
tro
l
Mito
xD
EB
Mito
x
Mito
xD
EB
(3)
Mito
x(3
)
Mito
xD
EB
100
DEB in Peritoneal Carcinomatosis: Results
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• 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
DEB in Peritoneal Carcinomatosis: Conclusion
