Intracavitary Hyperthermic

Perfusion-Chemotherapy (ICHP)
E. Dieter Hager
BioMed-Hospital, Bad Bergzabern, Germany

Workshop Hyperthermia, Cairo, December 21st, 2004

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 Methods of Intracavitary Hyperthermic
Perfusion ChTx

• Peritoneal Carcinomatosis
 Intraperitoneal (IPHC) • Malignant Ascites
• Pseudomyxoma peritonei
• i.p. disseminated Mesothelioma
• Neoadjuvant, Salvage &
Consolidation Therapy
• Adjuvant (?)
 Intrapleural (IPlHC)
• Malignant Pleural Effusion
• Pleural Carcinosis
• Malignant Pleuramesothelioma
 Intravesicular (IVHC)
• Recurrent Urothelial Carcinoma
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 Rationale for intraperitoneal Treatment
- Pharmacological advantages -
Spread of ovarian & stomach cancer occurs most frequently
Spread of ovarian & stomach cancer occurs most frequently
into
intothe
theperitoneal
peritonealcavity.
cavity.

 Higher
Higher concentrations
concentrations of ofcytotoxic
cytotoxicdrugs
drugswithin
within the
the
peritoneal
peritonealcavity
cavity following
followingi.p.
i.p. drug
drugadministration
administration
compared
comparedto toi.v.
i.v.application
application(i.p./plasma
(i.p./plasmaconcentrations
concentrations 18-
18-
1000
1000 fold).
fold).

Increased exposure time to antineoplastic agents due to

Increased exposure time to antineoplastic agents due to
peritoneal
peritonealspace
spaceto
toplasma
plasmabarrier
barrier

Reduced toxicity following i.p. application due to lower

Reduced toxicity following i.p. application due to lower
systemic
systemic concentrations
concentrations of
of cytotoxic
cytotoxic drugs.
drugs.
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 Pharmacological Advantage of I.P.
Administration Compared to Systemic
Drug Molecular Weight AUC Ratio* Synergism with
(i.p./plasma) Hyperthermia
Carboplatin 371 18 potentiating
Cisplatin 300 20 potentiating
Mitomycin C 334 71 potentiating
Methotrexate 455 92 independent
5-Fluorouracil 130 298 independent
Doxorubicin 544 474 additive
Mitoxantrone 517 620 additive
Paclitaxel 854 1,000 additive

* Ratio of antineoplastic agent in the dialysate compared with plasma levels

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Peri-/postoperative I.P. Chemotherapy
Preoperative (before surgery)
Perioperative
Intraoperative (during surgery)
Postoperative (early)

S. Fujimoto (Japan) / P.H. Sugarbaker (USA) / F. Gilly (France)/DeSimone

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Shenzhen 2004
 IPHC – Stomach Cancer
- intraoperative -

adjuvant Tx

Peritoneal disseminated stage

Fujimoto et al.: Cancer 1999; 85:529-34

Fujimoto et al.: 1991

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 Randomised Controlled Trials with Perioperative
Intraperitoneal Hyperthermic Chemoperfusion

Tumor site Experi- Con-trol No. of Relapse 4-year SR p-value Author

mental pts. after 2 yrs

Stomach cancer OP + IPHC 71 9 62% 0.04 Fujimoto 1999

OP 70 18 49%

Stomach cancer OP + IPHC 42 18 64% 0.2 Hamazoe 1994

OP 40 22 53%

Stomach cancer CT + OP + 55 9 52% Crookes 1997

IPHC
CT + OP

Abbreviations: RT: radiotherapy; CT: chemotherapy; MW: microwaves; RCT: randomised controlled trial; OT: open-label observational study; CR: complete
response; Rec: recurrence after adjuvant treatment; neoadj.: neoadjuvant; adj.: adjuvant

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 Percutaneous Intraperitoneal
Hyperthermic Perfusion-
Chemotherapie of Patients with
Recurrent Peritoneal Carcinosis from
Ovarian Cancer

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 Background

1. After induction CTx more than 80% of pts. with advanced

ovarian cancer (AOC) ultimately relapse from clinical remission.

2. CTx-refractory or -resistant pts. with peritoneal disseminated

AOC respond poorly to systemic therapies of all types.

3. The expected 1-yr OSR of these pts. is < 2%, depending from
size of largest residual tumor mass, time to progression,
performance status, and histological grading.

4. I.p. CTx application increases local concentrations of cytotoxic

drugs and improves RR‘s, but only moderately prolongs
survival, if prior systemic CTx failed.
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Median Overall Survival Time of Patients with
Advanced Cancer of the Ovary (AOC)
- Systemic Chemotherapy -
 Chemotherapy FIGO MOS
Stage [months]
 A) First-line after surgery
 - Single alkylating agents III 12-14
 - Platinum-based regimen s III 13-24
 - Paclitaxel + cisplatin III, IV 18-38

 B) Recurrent and platinum resistant (second-line)

 - Topotecan III, IV 10.8
 - Etoposide III, IV 10.8
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Patients Surviving 2 Years or Longer After Salvage Abdominal
Irradiation for Disease Found at Second-Look Surgery

 Residual Disease

 Microscopic Disease < 1 cm > 1 cm

 22%* 7%* 0%*

 *Young, R. C. et al.: Cancer of the Ovary. In: De Vita V.T. et al.: Cancer: principles and practice in oncology. 4th ed.
(1993)

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 Rationale for Hyperthermia (I)

1.1. Hyperthermia
Hyperthermiainduces
inducesapoptosis
apoptosis
(direct
(direct heat-related
heat-relatedcytotoxic/cytostatic
cytotoxic/cytostaticeffects)
effects)

2.2. Synergistic
Synergisticinteractions
interactionsof
ofheat
heatwith
withselected
selected
antineoplastic
antineoplasticagents
agents

3.3. Reduced
Reduceddrug
drugresistance
resistance(blood
(bloodperfusion,
perfusion,membrane
membranepermeability,
permeability,
metabolism)
metabolism)

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Rationale for Hyperthermia (II)

1.
1. Immunological
Immunological effects
effectsononcellular
cellulareffector
effectorcells
cellsand
and humoral
humoral
immune
immuneresponse
response (emigration,
(emigration,migration
migrationand
andactivation)
activation)

2.
2. Induction
Inductionof
ofcytokines,
cytokines, chemokines
chemokinesand
andheat
heat shock
shockproteins
proteins

3.
3. Modulation
Modulationof
of cell
cell adhesion
adhesionmolecules
molecules

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Objectives

 Feasibility
FeasibilityofofIPHC
IPHC
(tolerability,
(tolerability,safty
saftyand
andadverse
adverseevents)
events)

 Impact
Impact on
onoverall
overall median
mediansurvival
survivaltime
time(MST)
(MST)
&&survival
survival rate
rate(OSR)
(OSR)

 Effect
Effect on
onQuality
Qualityof
ofLife
Life(QoL)
(QoL)

 Feasibility
Feasibilityof
oflong-term
long-termtherapy
therapy

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Percutaneous Intraperitoneal Hyperthermic
Chemoperfusion
- repeated long-term Tx -

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IPHC-Unit

BioMed-Hospital
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Material and Methods (ascites/flooding)

Verres-Needle

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Material and Methods (perfusion/lavage)
Peritocat 1,5-2,5 mm

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 SLH-100 Perfusional Device

 Perioperative IPHP
 Percutaneous IPHP
 Intravesicular ICHP
 Endocavitary HT
 Isolated Extremity Perfusion
 Extracorporal Blood Perfusion

• Easy control of heat exchange

• European certification edh ICHS Shenzhen 2004
 Patients and Methods:
Study Design & Eligibility Criteria

Study
 Study Design:
Design:
 Prospective open lable, single-arm phase I/II-study
Prospective open lable, single-arm phase I/II-study

Inclusion
 Inclusion Criteria:
Criteria:
 Primary stage III or IV epithelial or stromal ovarian
Primary stage III or IV epithelial or stromal ovarian
cancer
cancer
 Advanced disseminated peritoneal carcinosis
Advanced disseminated peritoneal carcinosis
 Chemotherapy-refractory or -resistant patients
Chemotherapy-refractory or -resistant patients
at
at least
least after
after second-line
second-line CTx
CTx

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 Patients and Methods:
Eligibility Criteria

 Exclusion Criteria:
 No prior platinum- or paclitaxel-based regimen
 Extensive abdominal adhesions
 Distribution of fluid in compartments < 1.5 l
 Multiple bulky tumor masses in the abdomen (> 2 cm),
except of pts. with ascites
 Subileus symptomatic (advanced)
 History of heavy cardiac arrhythmia
 No informed consent

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 Methods:
Treatment (IPHC-Intervention)
 IPHC (qwx2-3) 2-4 l physiological saline

 IP Chemotherapy (qwx2-3) cisplatin 100 mg

 or carboplatin 450 mg
 or mitoxantrone 30 mg

 Temperatureinput 46-48 °C
 intraperitonal (set) 42-43 °C
 output 41-43 °C

 Perfusion Time 1 h at 42-43 °C

 Repetition q1w
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 Study Endpoints (IPHC-EOC)

 Primary Endpoint - Overall Survival Time/

Overall Survival Rate

 Secondary Endpoints - Clinical Benefit (QoL)

- Tumor Markers

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 Patient Characteristics (I):

 Total
Totalnumber
numberof
ofpatients
patientsaccrued
accrued 38
38
 Total
Totalnumber
numberof
ofpatients
patientsevaluable
evaluable 36
36
 Median Age (yrs.) [Range] 55
Median Age (yrs.) [Range] 55[22
[22––72]
72]
 Performance Status (WHO) II==36
Performance Status (WHO) 36%
% II
II==5353%
% III
III==11%
11%
 Sites
Sitesof
ofDisseminated
DisseminatedMetastases
Metastases nn[%]
[%]
–– Peritoneal
Peritonealcarcinosis
carcinosis 36
36[100]
[100]
–– Ascites
Ascites 17
17[47]
[47]
–– Lymph
Lymphnodes
nodes 88[22]
[22]
–– Liver
Liver 55[14]
[14]
–– Abdominal
Abdominalwall
wall 33[8]
[8]
–– Pleura
Pleura 22[6]
[6]
–– Spleen
Spleen 11[3]
[3]

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Patient Characteristics (II):

 Histology nn (%)
Histology (%)
 - Adenocarcinoma (serous, mucinous, endometriod)
- Adenocarcinoma (serous, mucinous, endometriod) 29
29(80)
(80)
 - Granulosa-stromal cell tumor 22(6)
- Granulosa-stromal cell tumor (6)

 --Undifferentiated
Undifferentiatedcarcinoma
carcinoma 22(6)
(6)
 --Unclassified
Unclassified 33(8)
(8)

 Grading n (%)
Grading n (%)
 - G1 = 2 (6) - G3 = 15 (42)
- G1 = 2 (6) - G3 = 15 (42)
 - G2 = 11 (30) --G4
- G2 = 11 (30) G4== 22(6)
(6)
 - unknown = 6 (16)
- unknown = 6 (16)

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 Prior Therapies and Tx-free Intervals
 Prior
PriorChemotherapy
Chemotherapyi.v.
i.v. Patients
Patients nn(%)
(%) av.
av.No.
No.ofofCourses
Courses
––cyclophosphamide
cyclophosphamide 32
32(89)
(89) 5.8
5.8
––platinum
platinum 34
34(94)
(94) 5.7
5.7
––paclitaxel
paclitaxel 18
18(50)
(50) 4.2
4.2
––others
others 18
18(50)
(50) 6.0
6.0

Average

Averagenumber
numberof
ofCTx
CTxcourses
coursesprior
priorto
to1st
1stIPHC
IPHC nn==12.5
12.5

Median

Mediantimetimefrom
from1st1stDxDxofofOC
OCto
to1st
1stIPHC-Tx
IPHC-Tx 17.9
17.9mos
mos
(Time to Progression/Resistance)
(Time to Progression/Resistance)

Last

Lasttreatment
treatmentfree
freeinterval
intervalpts.
pts.nn(%)
(%) <<44mos
mos 24
24(67)
(67)
(Median
(Median67
67days)
days) 4-12
4-12mos
mos 77(19)
(19)
>>12
12mos
mos 55(14)
(14)
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 IPHC – Treatment (EOC)

 Total number of IPHC-treatments 168

Total number of IPHC-treatments 168
 Follow-up time 3.3
Follow-up time 3.3 yrs.
yrs.
 Follow-up rate 94
Follow-up rate 94 % %
 Number of pts. still alive at time of 77 (censored)
Number of pts. still alive at time of (censored)
assessment
assessment

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Kaplan-Meier Curve for Survival from 1st IPHC-
Treatment of Patients with Ovarian Cancer
(all Patients n = 36)
Survival Function IPHT
1,0

,8

,6

,4
c u m . s u r v iv a l

,2

survival function

0,0 censored
0 1 2 3 4 5 6 7

[Survival from start of IPHT in years]

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Survival from 1st Dx of OC vs. 1st IPHC-Tx
(Kaplan-Meier Estimation)

Survival Function IPHT

1,0

,8

,6

,4

2,00 from IPHT

cum. survival

,2
2,00-censored

1,00 from dx

0,0 1,00-censored
0 2 4 6 8

[overall survival from dx vs. survival from IPHT in years]

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 Median Survival from 1st IPHC
Ascites vs. non-Ascites (Kaplan-Meier Estimation)

Survival Function IPHT

1,0

,8

,6

,4
P=0.4 ASCITES

yeas
c u m . s u r v iv a l

,2
1-censored

no 0

0,0 0-censored
0 1 2 3 4 5 6 7

[Survival from start of IPHT in years]

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Results: Median Survival Time (IPHC-OC)
(Kaplan-Meier-Estimation)
 From 1st IPHC-Treatment Median
(months)
Patients with Ascites ( n = 17) 15 ± 2
[range] [2 – 84+]

 Patients without Ascites (n = 19) 24 ± 2

[range] [4 – 55+]
all Patients (n = 36) 19 ± 4
[range] [2 – 84+]

 From 1st diagnosis of AOC:

 all Patients (n = 36) 49 ± 8
[range] [8 – 88+]

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 Results 2: Survival Rates from 1st IPHC
(Ascites vs. non-Ascites)

1-year
1-year 2-year
2-year 3-year
3-year 4-year
4-year 5-year
5-year
%% %% %% %% %%
From
From1st
1stIPHC-Tx:
IPHC-Tx:
 Pts.
Pts.with
withAscites
Ascites 63
63±±12
12 31
31±±12
12 25
25±±11
11 17
17±±10
10 17
17±±10
10
 Pts.
Pts.without
withoutAscites
Ascites 68
68±±11 45
45±±11
11 34
34 ±±11
11 15
15±±99 15
15±±99
 all
allPatients
Patients 65
65±±88 39
39±± 88 30
30±±88 16
16±±77 16
16±±77

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Adverse Events of IPHC in % of Total Tx
(n = 168)
 WHO-Grade
WHO-Grade 00 11 22 33 44
 Gastrointestinal
Gastrointestinal
––Nausea/Vomiting
Nausea/Vomiting 30
30 29
29 27
27 14
14 --
––Diarrhoe
Diarrhoe 97
97 22 11 -- --
––SGOT/SGPT
SGOT/SGPT 100
100 -- -- -- --
 Blood
Blood
––Leucocytes
Leucocytes 96
96 22 22 -- --
––Platelets
Platelets 99
99 -- -- -- 11
––Haemogobulin
Haemogobulin 92
92 55 33 -- --
 Renal
Renal
--Kreatinin
Kreatinin 92
92 66 22
 Fever 97 33 -- -- --
Fever 97 edh ICHS Shenzhen 2004
 Adverse Events of IPHC in % of Total Tx:
- Treatment Specific -

 Peritoneal irritations 5%*

Peritoneal irritations 5%*
 Subileus symptomatic 2%*
Subileus symptomatic 2%*
 Local reactions (vaccination metastases) 2/36
Local reactions (vaccination metastases) 2/36 pts.
pts.
 Bowel obstruction or perforation 0%*
Bowel obstruction or perforation 0%*
 Catheter related infections 0%*
Catheter related infections 0%*
 **%
%of
oftreatments
treatments(n
(n==168)
168)

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 IPHC
- Contraindications -

 Extensive
ExtensiveGI-adhesions
GI-adhesions

 Large
Largetumor
tumorvolume
volume

 Fistulae
Fistulae

 Subileus
Subileus(advanced
(advancedstage)
stage)

 Peritonitis
Peritonitis

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 Summary

1.1. IPHC
IPHC isis technically
technically feasible,
feasible, safe
safe and
and well
well tolerated
tolerated
2.2. High
High response
response rates rates are
are obtained
obtained in in pts.
pts. with
with recurrent,
recurrent,
chemotherapy
chemotherapy refractory
refractory oror resistant,
resistant, peritoneal
peritoneal
disseminated
disseminated AOC AOC
3.3. Reversal
Reversal of of drug
drug resistance
resistance isis possible
possible
4.4. Increase
Increase in in overall
overall survival
survival isis substantial
substantial
5.5. Quality
Quality ofof life
life can
can be
beimproved
improved
6.6. Adverse
Adverse drug
drug reactions
reactionsareareless
lesssevere
severe compared
compared to to
systemic
systemic chemotherapy
chemotherapy
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 Conclusions
1.1. Optimal
Optimal dosedose and
and schedule
schedule has has still
still to
to be
be defined
defined
2.2. IPHC
IPHC could
could be be recommended
recommended as as „palliative“
„palliative“ therapy
therapy for
for
pts.
pts. with
with CTx-refractory
CTx-refractory or or –resistent
–resistent peritoneal
peritoneal
carcinomatosis
carcinomatosis or or sarcomatosis
sarcomatosis fromfrom AOC AOC
3.3. IPHC
IPHC will
will be
be 11ooTx
Tx for
for elimination
elimination of of ascites
ascites
4.4. Could
Could bebe ofof advantage
advantage in in aa „salvage“
„salvage“ therapy
therapy setting.
setting.
Phase
Phase IIII studies
studies should
should bebeperformed.
performed.
5.5. IPHC
IPHC maymay be be possible
possible asas „consolidation“
„consolidation“ therapy
therapy ofof
stage
stage III/IV
III/IV pts.
pts. with
with PR
PR oror MR
MR to to standard
standard induction
induction
therapy.
therapy. RCTRCT should
should bebe performed.
performed.

edh ICHS Shenzhen 2004

Intravesicular Hyperthermic
Perfusion Chemotherapy (IVHC)

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Intravesicular Perfusion Hyperthermia with Catheter

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IVHC with Microwaves

Radiativ (intravesicular microwave antennae, f.e. SYNERGO®)

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IVHC of Pts. with Superficial Bladder Cancer with
intravesicular MW-Antennae (915 MHz) (neoadjuvant)

Colombo, R. et al.: J. Urol. 1996;155:1227-1252

Colombo, R. et al.: Eur. Urol. 1999;35 Suppl. 2
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Advanced Bladder Cancer

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Bladder Cancer – IVHC

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Bladder Cancer – PR/SD

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 Carcinoma of the Bladder:
Study Design & Eligibility Criteria

 Study Design:
 Prospective, Open Lable, Single-Arm Phase II-Study

 Inclusion Criteria:
 Recurrent and/or Progressive* Bladder Carcinoma
 rcTis,a,1/2 rcN0 rcM0, Rx, rG 2-3
 Prior TUR-B and Chemo-/Immunotherapy
 Indication for Cystectomy**
 Informed Consent
* infiltration (T-stage), dedifferentiation (G-Stage), Recurrence rate
**pt. refused/delayed surgery
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 Cancer of the Bladder- IVHP
Study-Endpoints

Primary Endpoints - Recurrence rate

- Recurrence free survival

Secondary Endpoints - Prevention of cystectomy

- Clinical benefit (QoL)
- Downstaging (T&G)

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Statistics

 Recurrent free survival Kaplan-Meier-Estimation

 Recurrence rates descriptive

 Intention-to-treat analysis

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Patient Characteristics I

 Number of Patients (male/female) 10 (8/2)

 Median Age (yr) (Range) 61 (50 - 68)
 Karnofsky Index 100 % (n = 4) 90 % (n = 6)
 Stage n
rc T1 8
r T2 2
 Grading
 r G2 7
 r G3 3
 Histology
 urothelium carcinoma 9
 unknown 1 edh 09/01
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 Patient Characteristics II
Recurrence before IVHP

 Av. No. of total Recurrences/pt. (range) 6.3 (1 - 12)

 total Recurrence Rate (RR*) (range) 15.5 (7 - 28.7)

number of positive cystoscopies

* RR = -----------------------------------------
months reexaminations

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 Treatment and Statistics

 Total No. of IVHP- Tx 56

 Mean No. of IVHP-Tx/Pt. (Range) 4.9 (1-13)

 Mean Follow-up Time* 74 months

 Follow-up Rate 100 %

 No. Pts. Alive at Time of Estimation 9

* since last IVHP

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 Prior Chemotherapy and IVHP

 Prior Chemotherapy* Pts. n av. # of Courses

Mitomycin 5 4
Doxorubicin 2 10

 Mean Time from 1st dx to 1st IVHP-Tx: 2.8 yrs (0.3 - 7.6)

 *intravesical

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Cancer of the Bladder
IVHP - Intervention

 Intravesical Perfusion Volume 100-300 ml saline dialysate

 Intravesical Chemotherapy Mitomycin (MMC) 10 mg

 Intravesical Temperature Input T 46-48°C

 Intravesical T 42-43°C
 Output T 41-42°C

 Perfusion Time at 42-43o C 1h

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 Results: Case reports of pts. with
Reccurent Bladder Cancer
K.E. * 03.12.40

2
1,8
1,8
1,6
Relapses/Year

1,4
1,2
1
0,8
0,6
0,4
0,2
0
0
6/3,3 Years 0/3,5 Years

Prae/Post IVHT(n = 1 treatment) U.G. *29.01.26

1,4
1,25
1,2

1
Relapses/Year

0,8

0,6

0,4

0,2

0
0
9/7,2 Years 0/3,9 Years

Prae/Post IVHT (n = 4 treatments)

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Case Report B.M.

Bladder Cancer (case report B.M.) - Recurrences

6 MMC, KLH

5
IVHC

4
No Foci

0
Sep 96 Mrz 97 Sep 97 Mrz 98 Sep 98 Mrz 99 Sep 99 Mrz 00 Sep 00 Mrz 01

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Results: Interavesicular Hyperthermic Perfusions-Chemo-
therapie (IVHC) in Patients with recurrent Bladder Cancer

IVHT - Blasenkarzinom
4,00

3,50

3,00

2,50
Rezidivrate/Jahr

Recurrence-prae
2,00
Recurrence-post
Pat. 1: zystektomiert
1,50

1,00
alle Patienten
0,50

0,00
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Patienten-Nr.

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Results: Recurrence Rate of Bladder Cancer
after IVHC - Kaplan-Meier-Estimation -

p < 0.01

edh ICHS Shenzhen 2004

Adverse Effects of IVHP in % of Total Treatments (n = 39)

 WHO-Grade 0 1 2 3 4

 Pain 100 - - - -

 Infection/Fever 100 - - - -

 Cystitis 86 14 - - -

 Uremia 100 - - - -

edh 10/98
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 Summary & Conclusions

 IVHP combined with CTx seems to be a feasible, safe and

promising approach for the treatment of recurrent bladder
cancer

 Chemotherapy-resistance may be reduced by heat

 Recurrence rate/recurrence-free suvival decreased

significantly

 Bladder-sparing seems to be possible by IVHC

 The efficacy should be demonstrated in larger randomized

trials
edh ICHS Shenzhen 2004
Conclusions:
Indications for IVHP-CTx

 Neoadjuvant therapy (downstaging)

 Adjuvant therapy (relapse prophylaxis after TUR-B)

 Bladder-sparing therapy for superficial and invasive,

recurrent bladder cancer

edh ICHS Shenzhen 2004

Recurrence Rate of Bladder Cancer after IVHC

Bladder Cancer - IVHT

1.0

0.8
GROUP
1
Probability

0.6 2
3

0.4

0.2

0.0
0 500 1000 1500 2000 2500
Time: to recurrence/recurrence-IVHT
edh ICHS Shenzhen 2004
 Randomised controlled and observational trials with
intravesicular hyperthermic perfusion chemotherapy

Tumor site Experi-mental Con-trol No. of OR [%] OR [%] Survival Re- Ref.
pts. Control with HT benefit marks

Bladder, neoadj. MW + CT CT 52 CR: 22 CR: 66 Yes RCT 53

Bladder, adj. MW + CT CT 58 Rec: 64 Rec: 15 Yes RCT 54

Bladder, recurrent hyperthermic   10   90 Yes OT 55

perfusion +
CT

Abbreviations: RT: radiotherapy; CT: chemotherapy; MW: microwaves; RCT: randomised controlled trial; OT: open-label observational study; CR: complete
response; Rec: recurrence after adjuvant treatment; neoadj.: neoadjuvant; adj.: adjuvant

edh ICHS Shenzhen 2004

Summary & Conclusion
 Long-term, percutaneous or intravesicular
hyperthermic perfusion-chemotherapy is one
of the most powerful new treatments in
oncology

 It is feaseable and has minimal side effects

compared to standard chemotherapy

 It can be repeated oftenly (> 30 Tx)

edh ICHS Shenzhen 2004