HAIC &
Toray Anthron P-U Catheter
杏昌生技股份有限公司
Contents
HAIC：
●Advantages of HAIC
●Paper Discussion
Toray Anthron P-U Catheter：
●What is APUC？
●Animal test
●Types of Anthron P-U Catheter
●Instructions for implantation
●APUC先端固定留置法
●Regimen
●Peroration
HAIC
〈Hepatic Arterial infusion chemotherphy〉
Advantages of HAIC
Increase the local drug concentration
Good response rate
Prolong the survival
Reduction in systemic side effects
Made it possible to perform treatment on an
outpatient basis
Paper Discussion
HCC with PVTT
Liver Metastases from Colon Cancer
Liver Metastases from Gastric Cancer
Liver Metastases from Breast Cancer
HCC with PVTT
Dr. Tanaka
Year Researcher Pt's pattern
1997 M. Tanaka
(Kurume U)
M. Tanaka
1996~1 (Kurume U)
997
1999 ~ M. Tanaka
2000 (Kurume U)
ad. HCC with
PVTT
ad. HCC with
PVTT
ad. HCC with
PVTT
Patient (n=)
Regimen
9
10 mg cisplatin /
250 mg 5-FU
10 mg cisplatin /
250 mg 5-FU
44.40%
7 mg cisplatin /
170 mg 5-FU
48%
77
48
Response Rate Survival / Median SV
45%
3 yr-40%
14.9 Mons
1-yr, 2-yr, 3-yr /
55.8% , 27.6% ,
18.3%
45% , 31% , 25% /
36.1 Ms & 5.4 Ms
Publish
American Cancer
Society(1997)
American Cancer
Society(2002)
HCC with PVTT
國泰醫院
Year
Researcher Pt's pattern Patient (n=)
ad. HCC
2000/1/1~2003/5/31 (國泰醫院)
with PVTT
18
Regimen
10 mg cisplatin
/ 250 mg 5-FU
Response Rate Survival / Median SV
33%
Publish
3,6,9,12,18World J
month/83%,72%,50% Gastroenterol
,28%,7%
(2003)
Liver Metastases from Colon Cancer
Dr. Kemeny ( Memorial Sloan-Kettering Cancer Center )
Pt's pattern
Researcher
Dr. Kemeny
HAIC +
systemic
systemic
after resection of Hepatic
Metastases from Colorectal
Cancer
Patient (n=) overall survival at 2 yrs
156
86%
82
72%
median
survival
Publish
The New
England
Journal of
59.3 months Medicine
72.2 months
●receive 6 cycles of HAI with floxuridine and dexamethasone plus intravenous
fluorouracil, with or without leucovorin(Group A), or 6 wks of similar sys alone (Group
B). (p=0.03)
●At 2 yrs,the risk ratio of B/A=2.34.
Liver Metastases from Colon Cancer
Arai, M.D.
Target lesion
Patients Regimen Response Rate Survival
Arai (1992) Liver metastases from gastric carcinoma 40 5-FU 72% 17 months
Arai (1997) Liver metastases from colorectal carcinoma 32 5-FU 78% 25.8 months
Liver Metastases from Colon Cancer
Tetsuo Taguchi, M.D.
Patient characteristics (n=32)
Sex: male 24 & female 8
Age: 59.7< 60.8<70
Extra hepatic lesion:
(-) 21
(+)11
Degree of liver involvement:
<30%
11
30%~60%
16
60%<
5
Histology:
well
6
moderately
24
unknown
2
Regimen
5-FU 1000mg/m2/5hrs qw continuously
(WBC>=2000 and platelets>=50000)
Osaka University Medical School
Colorectal cancer
Side effects and complications
nausea (grade 1)
22%
nausea (grade 2)
9%
dizziness
3%
GTP elevation
13%
bile lake
9%
HA occlusion
22%
Response
CR PR NC PD
Response rate
4
20
7
1
75% (24/32)
50% survival
overall 22.0 months
(7.5+~40.0+)
extra hepatic lesion(-)
25.0 months
extra hepatic lesion(+)
16 months
Liver Metastases from Gastric Cancer
Tetsuo Taguchi, M.D.
Patient characteristics (n=56)
Sex: male 29 & female 11
Age: 53.7< 62.3<70.9
Extra hepatic lesion:
(-) 20
(+)20
Degree of liver involvement:
<30%
12
30%~60%
16
60%<
12
Histology:
well
6
moderately
24
poorly
unknown
2
2
Regimen
5-FU 330mg/m2qw bolusly
(WBC>=2000 and platelets>=50000)
Osaka University Medical School
Gastric cancer
ADR 20mg/m2 or EPIR 30mg/m2 q4wbolusly
(WBC>=3000 and platelets>=100000)
MMC 2.7 mg/m2q2w bolusly
(WBC>=3000 and platelets>=100000)
Side effects and complications
myelo-suppression (>=grade 3) 35%(14/40)
narsea (>=grade 2)
10%(4/40)
HA occlusion
5%(2/40)
Response
CR PR NC PD NE Response rate
6
20
6
4
50% survival
overall
extra hepatic lesion(-)
extra hepatic lesion(+)
4
72% (26/36)
15 months(3+~66)
17.0 months
9 months
Liver Metastases from Breast cancer
Tetsuo Taguchi, M.D.
Osaka University Medical School
Patient characteris tics (n=56)
Breas t cancer
Sex: All female
Age: 38.7<48.0<57.3
Degree of liver involvement:
<30%
13
30%~60%
25
S ide effects and complications
60%<
18
myelos uppres s ion (>=grade 3)
41%
Extra hepatic les ion:
hepatic arterial occlus ion
23%
(-) 9
(+)47
gas troduodenal toxicity
20%
Prior s ys temic chemo/endocrine therapy:
(ulcer, gas tritis , s ubjective s ymptoms )
(-) 6
(+)50
Res pons e
Regimen
CR
PR
NC
PD
NE
Res pons e rate
to 42 patients
10
33
6
4
3
81% (43/53)
5-FU
330mg/m2
qw
bolus ly S urvival
ADR
20mg/m2
qw
bolus ly overall
12.5months (3~64+)
MMC
2.7mg/m2
qw
bolus ly pleural/peritoneal carcinomatos is :
to 42 patients
(-) 14.0months
(+)9.0 months
5-FU
330mg/m2
qw
bolus ly Res pons e:
EPIR
20mg/m2
q2w
bolus ly
(-) 16.0months
(+)5.0 months
Causes of death in 35 responders
pleural/peritoneal carcinomatosis
liver metastases
lung metastases
others
54%
14%
9%
23%
Toray Anthron P-U Catheter
What is Anthron ?
Heparin
-
Heparin
-
Heparin
Heparin
-
Heparin
Heparin
Heparin
Heparin
Heparin
Heparin
Heparin
-
Anthron is hydrophilic polymer
which is ionically bound Heparin
and originally developed by
Toray.
Anthron continues to release
Heparin into blood for a long
term period which prevents
thrombus formation.
Raw material of this catheter
●Tube : Polyurethane
●Coating on outer surface : Anthron
●Coating on inner surface : Anthron
about 8 cm from distal end.
(Catheters with entire inner surface coated is under
development.)
●The surface of catheter becomes slippery after
moistening, then, manipulation(操作) in blood
vessel is smooth.
Heparin Release Curve from
Anthron P-U Catheter
10-2
Anthron
10-3
10-4
10-5
10-6
0
10-1
BzCl-Hep
20
40
Time (hour)
60
Eluted Heparin Amount
( units/ cm2 min.)
Eluted Heparin Amount
( units/ cm2 min.)
10-1
BzCl-Hep
10-2
Anthron
10-3
10-4
10-5
10-6
0
100
200
300
Time (days)
400
Concept & Target
★Catheter for long-term inderwelling★
★
Catheter for chemotherapy
★
Animal test
Material & Method：
●Material:
silicon catheter
Anthron P-U Catheter
●Animal:
Dogs(Biegle)
●Indwelling place:
from femoral vein to
vena cava
●Indwelling term:
6 months
Test results(1)
Analysis of blood components after indwelling
RBC
WBC
7E+2
150E+4
666
623
6E+2
132
616
597
125E+4
115
112
Anthron
silicone
Female
α2-globlin
Seg-Neutrophile
100%
10%
5.3
50%
0%
Male
Anthron
silicone
Female
Male
5%
4.9
4.8
Anthron
57.8
silicone
56
7.3
70.6
Female
68.6
0%
100E+4
Male
Anthron
silicone
Female
5E+2
Male
107
Test results(2)
Frequency of pulmonary embolism(n=87)
Observation by optical microscopy
100%
Anthron
80%
60%
40%
30%
20%
0%
Silicone
1%
Control
5%
silicone
Anthron
Silicone : higher risk of PE
Test results(3)
Frequency of phlebitis on indwelling place(n=87)
Observation by eyes
100%
Anthron
81%
80%
Silicone
60%
40%
20%
0%
Observation by optical microscopy
21%
Control
18%
silicone
Anthron
Anthron
Frequency of phlebitis where the catheter is placed
Silicone
Test results(4)
Frequency of thrombus formation on catheter surface
Observation by SEM
100%
80%
60%
47%
40%
24%
20%
0%
Anthron
0%
Control
silicone
Anthron
Anthron:lower risk of
thrombus formation due to
catheters indwelling
Silicone
Types of Anthron P-U Catheter
Proximal portion
Catalogue No.
Distal portion
Tapar length
Length
Hardness
0.46mm (0.018")
2.5cm
72.5cm
S oft type
0.46mm (0.018")
20cm
90cm
S oft type
Fr. size
Guide wire
Fr. size
Guide wire
PU5070S DS T
5
0.89mm (0.035")
2.7
PU5090S DS T
5
0.89mm (0.035")
2.7
C atal ogue No.
Re gul ar Type
Ri nge d Type
Fr. size
Ring O.D. (mm)
Length(cm)
Hardness of catheter
Suitable guidewire
PU6070HC S
6
-
70
Hard
0.97(0.038)
PU5070HC S
5
-
70
Hard
0.89(0.035)
PU5070HDS
5
-
70
Hard
0.89(0.035)
PU5070SDS
5
-
70
Soft
0.89(0.035)
PU5090HC S
5
-
90
Hard
0.89(0.035)
PU5000HC S
5
-
100
Hard
0.89(0.035)
PU3370HC S
3. 3
-
70
Hard
0.46(0.018)
PU6035SAR
6
3
35
Soft
-
PU6070SAR
6
3
70
Soft
-
PU5035SAR
5
2. 7
35
Soft
-
PU5070SAR
5
2. 7
70
Soft
-
5
-
70
Hard
0.89(0.035)
He adhunte r APU5070HDAA
Pre Shape d
Type
C obra A
PU5070HDC B
5
-
70
Hard
0.89(0.035)
Hook A
PU5080HDC C
5
-
80
Hard
0.89(0.035)
RH-A
PU5080HDC G
5
-
80
Hard
0.89(0.035)
Twi st
PU5070HDC Y
5
-
70
Hard
0.89(0.035)
Instructions for implantation
Instructions for implantation
●Check the tumor location using an angiographic
catheter.
If necessary, redistribute the blood circulation
●Insert a guidewire into the angiographic catheter
●The guidewire must not be removed into the
vessel. Then remove the angiographic catheter.
●Insert an indwelling catheter into the
vessel by the Seldinger technique.
●Slide in the catheter through the
guidewire until it reaches the target
vessel.
●Indwell the catheter at the site to be treated,
assuring the position of the end of the
catheter with the radioscope. To reduce
the risk of the dislocation of the catheter,
coil down the catheter into the aorta.
●Cut the catheter to adjust the length
appropriately
●Prepare the ST301C or ST305C
manufactured by B. Braun Aesculap.
ST301C
●Insert a lock for ST301C or ST305C
over the catheter ring, over the
proximal end of the catheter.
ST305C
●Insert the exit cannula of ST301C or
ST305C into the catheter, as in the
following illustration.
●Fix the lock ring onto the portal.
IA Catheter 的先端固定留置法
Conventional percutaneous method
CHA-coil 法
SPA-coil 法
GDA-coil法
Converntional percutaneous method
RGA and GDA were
embolized and the
indwelling catheter was
inserted to PHA
CHA-coil 法
RGA was embolized and the
indwelling catheter was
inserted into PHA, then
CHA was embolized by
coils.
SPA-coil 法
Embolization of RGA,
GDA, LGA and DPA were
performed before the
following catheter
placement. The indwelling
catheter was inserted to
SPA with the catheter-tip
fixed employing steel coils
and NBCA-Lipiodol mixture,
the side hole of which was
placed on the celiac artery.
GDA-coil 法
Embolization of RGA was
performed before the
following catheter
placement. The indwelling
catheter was inserted to
GDA with the catheter-tip
fixed employing steel coils
and NBCA-Lipiodol mixture,
the side hole of which was
placed on CHA.
各種留置法的比較
Regimen
For HCC
(1) High dose：5-FU+Ifα(for one month)
IF
一
IF
二
三
IF
四
5-FU (1600mg/body)
Response Rate：50%
五
六
日
一
5-FU (1600mg/body)
For HCC
(2) Low dose：5-FU+CDDP(for one month)
一
二
三
四
五
六
5-FU (250mg/body)+CDDP (10mg/body)
Response Rate：60%
日
一
For HCC
(3) EEP (for one month)
Etoposido 80~90mg/body
一
二
三
四
CDDP 70mg/body
EP 50mg/body
Response Rate：43%
五
六
日
一
CDDP 70mg/body
EP 50mg/body
For Metastasis
WHF
5-FU 1600mg/body for 5-FU
一
二
三
5-FU 1600mg/body for 5-FU
四
One-time/week
五
六
日
一
Peroration
HAIC + Toray Anthron P-U
Catheter is the best.