Intraarterial Treatment for Pancreatic Cancer

May 5 2016
GEST
Toshihiro Tanaka, MD, PhD
Dept of Radiology, IVR Center,
Nara Medical University,
JAPAN
Toshihiro Tanaka, M.D., Ph.D.
• No relevant financial relationship reported
Before
2000
5FU vs.
GEM
GEM vs.
Marimastat
GEM vs.
GEM+Cis
20012003
GEM vs.
GEM+5FU
GEM vs.
BAY129566
GEM vs.
GEM+Cis
GEM vs.
GEM+Iri
20042005
GEM vs.
GEM+Pemet
GEM vs.
GEM+Cis+Ep
i+5-FU
GEM vs.
GEM+Oxali
GEM vs.
GEM+Alimta
GEM vs.
PEFG
GEM vs.
GEM+tipifarn
i
20062007
GEM vs.
vs.
GEM
GEM+Erlotinib
GEM+Erotinib
GEM vs.
GEM+Cap
20082010
GEM vs.
GEM+Avasti
n
GEM vs.
GEM+Cap
6.2 months vs
GEM vs.
5.9months
GEM+Herce
GEM vs.
GEM+OFF
GEM vs.
GEM+Iritotec
a
GEM vs.
GEM+Exateca
n
GEM vs.
GEM+Cis
p
GEM vs.
GEM+Ero+
Beva
GEM vs.
GEM+Oxali
GEM vs.
GEM+Cis+doce+
Iri
20112013
GEM
GEM+ Beva
GEM+LV5FU
2-CDDP
GEM vs.
GEM+LY293
1
GEM vs.
GEM+Cis
GEM vs.
GEM+Cetu
GEM
GEM
vs.vs.
FOLFIRINOX
FOLFIRINOX
GEM vs.
GEM vs. GEM+
GEM+
nabPTX
nabPTX
RR 23% vs 7%
RR 31% vs 9%
To improve a therapeutic outcome without severe
toxicities, the development of novel therapeutic
strategy is required.
FOLFIRINOX
Nab-PTX + Gem
Neutropenia
46%
38%
Fatigue
23%
17%
Neuropathy
9%
17%
Head cancer
Body cancer
CA
SMA
Both the pancreatic head and the body cancer
required chemo-infusion CA
from CA and SMA
SMA
Tanaka T. AJR 2007;189:421-8
Double catheter placement
Intraarterial
5FU 333mg/m2/day X5daysX 5weeks
RT
50Gy / 25 fraction
Maintenance
GEM 1000mg/m2/qw iv
From CA
Before
After Intra-arterial 5FU+RT
From SMA
Response rate: 70%
Response rate 70%
MST: 11 months
(95%CI, 10.011.9)
Adverse
Events
We hypothesized…..
Tanaka T. et al. AJR 2009;192:168-77
avoiding the adverse effects
Single Celiac Arterial Supply
Pancreatic Head Cancer
Before
After
CA
from CA
After alteration
from CA
Alteration of blood supply
from SMA
SMA
lumber arteries
fine mesenteric branches
Invasion to the dorsal site
Invasion to the caudal site
Tanaka T. et al. AJR 2009;192:168-77
Tanaka T et al. AJR 2012; 198:1445-52
5-FU ▲ mg/m2
(Intra-arterial)
GEM 1000mg/m2
(Intra-venous)
Dose escalation of 5-FU
Level
Level
Level
-1: X= 500
1: X= 750
2: X= 1000 mg/m2
▲
Ｏ
day1
▲
Ｏ
day8
▲
Ｏ
day15
Tip
Implantable Port
Side hole
CT before treatment
Before Treatment
Intra-arterial 5-FU 1000mg/m2 plus full-dose systemic GEM
After 3 cycles
No adverse events
N=20 (metastatic 18, locally advance 2)
No DLT
RD: 5-FU 1000 mg/m2
No severe toxicity
RR: 68.8%
MST: 9.8 m vs 5.7 m
(5-FU ia+GEM) (GEM alone)
MST 9.8 mos
PFS: 6.0 m
OS:
9.8 m
Our
study
GEM alone
Tanaka T. et al. JVIR 2010;21:116-21
Pancreas head
ia: With
SMA occlusion
CA
5FU
iv
ia: Without
SMA occlusion
SMA:
occlusion
AUCs of 5-FU in Pancreas
CA19-9
Tanaka T et al. Anticancer Res 2011,31:3909-12
200
180
160
140
120
100
80
60
40
20
0
RT
Small radiation field
Arterial infusion
2007.6 2007.7 2007.8 2007.9 2007.10 2007.11 2008.1 2008.2 2008.4
Tumor Reduction after 5-FU ia
Survival time: 42 months
Hepatic Arterial Therapy with Drug-Eluting Beads in
the Management of Metastatic Pancreatic
Carcinoma to the Liver: A Multi-Institutional
Registry.
Kototyan R, et al. J Oncol 2012
 Pancreatic adenocarcinoma N=6
 Refractory Chemotherapy,
 Concurrently chemotherapy, FOLFOX 2, GEM2, FOLFIRI1, Tarceva 1
Response rate 80% , OS 9.3 mos
75yrs. M Pancreatic Body Cancer with Liver Mets
DEBIRI-TACE combined with FOLFOX
Before TACE
1 mo after TACE
15 mos after TACE
CA19-9
600
DEBIRI-TACE
500
400
300
CA19-9
200
100
0
FOLFOX
62yrs. M
Pancreatic Cancer with Liver Mets
Refractory for Previous
Standard
Chemotherapies
(Gemcitabine, S1,
Elpamotide)
Before
Before 1st TACE
1 mo after 1st TACE
After
22 mos after 1st TACE
CA19-9
4000
3500
3000
2500
2000
1500
1000
500
0
DEBIRI-TACE
CA19-9
Intra-arterial therapy has a high
potential to become the
breakthrough in the treatment of
pancreatic cancer.