IS#THERE#A#ROLE#FOR## INTRA-ARTERIAL#THERAPY##OR## ISOLATED#LIVER#PERFUSION?

IS#THERE#A#ROLE#FOR##
INTRA-ARTERIAL#THERAPY##OR##
ISOLATED#LIVER#PERFUSION?!
Pr!Olivier!Detry!
Department!of!Abdominal!Surgery!&!Transplanta;on!
CHU!Liège,!Université!de!Liège!
!
IS#THERE#A#ROLE#FOR##
INTRA-ARTERIAL#THERAPY##OR##
ISOLATED#LIVER#PERFUSION?#
YES!!
Pr!Olivier!Detry!
Department!of!Abdominal!Surgery!&!Transplanta;on!
CHU!Liège,!Université!de!Liège!
!
Disclosure!statement!
•  No!financial!rela;onships!to!disclose!!!
CRC!Liver!Mets!
•  25%!of!pa;ents!with!CRC!have!synchronous!liver!
Mets!at!;me!of!diagnosis!
•  50%!of!pa;ents!will!develop!metachronous!Mets!!
•  R0!resec;on!remains!the!standard!of!treatment!
and!the!only!hope!for!cure!and!longOterm!survival!
•  Survival!aPer!resec;on:!25!to!50%!at!5!years!
•  50%!of!recurrences!within!2!years!
•  25!to!50%!of!recurrences!are!intrahepa;c!only!!
CRC!Liver!Mets!
Liver!vascularisa;on:!
66!%!Portal!vein!
33!%!Hepa;c!artery!
!
MTST!vascularisa;on:!
>!80!%!Hepa;c!artery!
!
CRC!Liver!Mets!!
and!intraarterial!therapy!
•  Intra!arterial!chemotherapy!
•  Radioembolisa;on!YXrium!
•  Isolated!liver!perfusion!
IntraOarterial!chemotherapy!
•  Adjuvant!IA!chemotherapy!
•  Irresectable!MTST!
! !O!pallia;ve!(1st!or!2nd!line)!
!
•  BeXer!compared!to!old!style!chemotherapy!
•  Discussed!compared!to!modern!iv!therapy!
! !!
Goere,!Ann!Surg!2013;!257:114O120.!
Pallia;ve!IA!chemotherapy!
IntraOarterial!chemotherapy!
•  ideal!for!mul;ple!CRC!MTST!isolated!to!the!
liver!
O!irresectable!
O!aPer!resec;on!>!4!lesions!
•  Technically!challenging!
O!thrombosis!
O!infec;on!
•  Placement:!surgical!or!radiological!
Surgical!placement!
IntraOarterial!chemotherapy!
•  Need!for!beXer!prospec;ve!studies!comparing!
modern!IV!and!IA!chemotherapy!both!in!
pallia;ve!and!postopera;ve!condi;ons!
YXriumO90!radioemboliza;on!
•  TheraSpheres!(20O30!microns)!
•  SIRSpheres!(20O60!microns)!
•  First!line!therapy!
•  Second!or!third!line!chemotherapy!
•  Salvage!for!chemorefractory!pa;ents!
Selec;ve!treatmetn!of!the!right!liver!MTST!
+!5!months!
+!15!months!
Isolated!liver!perfusion!
•  High!concentra;on!of!chemotherapy!
•  High!temperature!
•  melphalan!+!TNFOα!
•  oxalipla;n!
•  Ocular!melanoma!MTST!
•  NeuroOendocrine!MTST!
•  CRC!MTST!
Isolated!liver!perfusion!
Ann Surg Oncol (2009) 16:385–394
DOI 10.1245/s10434-008-0179-5
ORIGINAL ARTICLE – HEPATOBILIARY AND PANCREATIC TUMORS
A Phase I Study of Hyperthermic Isolated Hepatic Perfusion with
Oxaliplatin in the Treatment of Unresectable Liver Metastases
from Colorectal Cancer
Herbert J. Zeh III, MD1, Charles K. Brown, MD, PhD1, Matthew P. Holtzman, MD1, Merrill J. Egorin, MD2,3,
Julianne L. Holleran, BS2, Douglas M. Potter, PhD4, and David L. Bartlett, MD1
1
Division of Surgical Oncology, Department of Surgery, University of Pittsburgh School of Medicine, Suite 417 UPMC
Cancer Pavilion, 5150 Center Ave., Pittsburgh, PA 15232, USA; 2Molecular Therapeutics/Drug Discovery Program,
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA; 3Division of Hematology/Oncology, Department of
Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA; 4Biostatistics Department, Graduate
School of Public Health and Biostatistics Facility, University of Pittsburgh Cancer Institute, University of Pittsburgh,
Pittsburgh, PA 15213, USA
Isolated Hepatic Perfusion with Oxaliplatin
387
years).
We conclude
that 1hyperthermic
with
oxaABSTRACT
perfusion (IHP)
a proven
bypass hadIsolated
beenhepatic
established,
the isIHP
circuit([4was
conTABLE
OxaliplatinIHP
dose
escalation
scheme
2
liplatin
was
safe
and
feasible
at
a
dose
of
40
mg/m
approach
for
regional
delivery
of
chemotherapy
in
patients
.
The
structed. The GDA was ligated distally. The inflow cannula
Planned
Actual number of
Dose vascular
Oxaliplatin
with unresectable primary and metastatic tumors of the
ability to obtain complete
isolation with open
IHP number
2
for
perfusion
was
positioned
in
the
proximal
GDA,
and,
)
of
patients
patients enrolled
level
dose
(mg/m
liver. Most trials of IHP have utilized melphalan as the
was confirmed. The response rate in this small phase I study
once
secured,
a cross
was
placed
the
entire
active
drug
in the perfusate.
We clamp
performed
a phase
I trial across
to
was
encouraging.
1
5
1
1
evaluate
the
efficacy,
safety,
and
maximum
tolerated
dose
porta hepatis, including the common hepatic artery, bile
(MTD) of oxaliplatin delivered by hyperthermic isolated
2
10
1
1
duct, and portal vein. The perfusion outflow cannula was
hepatic perfusion. A phase I dose-escalation trial of
Cancer of the colon
and rectum20
is the third most frequent
1
1
inserted into
the retrohepatic
IVC via
percutaneous
can-in the 3USA, and accounts
hyperthermic
IHP with
oxaliplatin in patients
withaunresite of cancer
for approximately
a
4
40
3–6
6
sectable
metastatic
colorectal
scheduled
undergo
nulation
of the
right cancer
femoral
veintoand
a tourniquet
was
150,000 new
cases annually.1 Hepatic metastases as the sole
placement
a hepaticthe
arterial
infusion
pump was
3–6
1b
dominant site of 5
life-limiting 60
disease occur in approxiplaced ofaround
cannula
at (HAI)
the level
of theorsuprarenal
carried out. Thirteen patients were enrolled between
mately 20–50% of patients
with colorectal
cancer.2 Median
6
90
3–6
0
infrahepatic
IVC.
The
suprahepatic
IVC
was
then
crossNovember 2003 and September 2006. Dose-limiting venosurvival of patients with untreated colorectal cancer hepatic
2
7
120
3–6
0
clamped,
and
thisat had
been
vascular
occlusive
disease
wasonce
observed
60 mg/m
. Ataccomplished,
the MTD
metastases
ranges from 4 to 12 months.3 Complete surgical
2
3–6
0
of isolation
40 mg/m only
minor
transient
liver dysfunction
was
resection
of isolated8colorectal 150
cancer hepatic metastases
of the
liver
was considered
complete,
and perfuobserved. Ultrafilterable platinum area under the curve and
results in 5-year
survival rates between 32% and
a
sion was initiated. The perfusate consisted
of overall
MTD
maximum concentration delivered by IHP increased non58%.4–8 Unfortunately, only 10–20% of patients with
b
approximately
500platinum
ml Ringer’s
lactate
to which
9
linearly
with dose as did
concentrations
in liver
of grade
V VOD
and fulminant
hepatic failure
colorectalwere
metastases toDLT
the liver
are eligible
for resection.
biopsies
at the
of the red
60 min
IHP. cells.
Seventy-Once
addedobtained
2 units
of end
packed
blood
perfusion
Systemic
chemotherapy is the predominant treatment for
seven percent of patients had a [50% decrease in serum
patients with unresectable liver metastases from colorectal
IS#THERE#A#ROLE#FOR##
INTRA-ARTERIAL#THERAPY##OR##
ISOLATED#LIVER#PERFUSION?#
YES!!
Pr!Olivier!Detry!
Department!of!Abdominal!Surgery!&!Transplanta;on!
CHU!Liège,!Université!de!Liège!
!
Thanks!!