1

DSM – TACE in comparison with c- and DEB-TACE

EmboCept® S, DSM 35 – 50*

*) DSM = degradable starch microspheres (Amilomer)

2

DSM (EMBOCEPT® S) IN COMPARISON

EmboCept® Svs. DC Beads Pharmacokinetics Clinics Therapeutic/technical recommendation

vs. lipiodol

3

CHEMOEMBOLIZATION – DSM-TACE

EmboCept® S - parameters

• cross-linked, partially hydrolyzed starch

• polymere matrix

• median diameter: 50 /um (lodge in precapillary vessel area)

• half-time: app. 35-40 min.

• degadation by -amylase

• fragments: 100 - 106 Dalton (water-soluble)

4

Angiographic documentation of vessels

permanent embolization N collateral tumor

vessels

6 h 4 4

4 h 5 3

2 h 5 0

CHEMOEMBOLIZATION – advantages of a degradable material

Persson BG et al. World J Surg 1987;11(5):672–7

5

DSM (EMBOCEPT® S) VS. DC BEADS

pharmacokinetics

clinics

therapeutic/technical recommendation

6

AUC: 10 mg 5-FU i.a. versus 10 mg 5-FU + 6 mg Amilomer i.a.

10000

20000

40000

50000

AU

C (

15

-12

0 m

in)

µg

/g*m

in655

62655

1704

27822

5-FU i.a. 5-FU+Amilomer i.a.0

95 x

60000

10 mg 5-FU i.a.

0 15 30 45 60 90 Min0

10

20

30

40

50

60

70

µg

/g 5

-FU

Tumor

Liver

25,09 µg/g

58,65 µg/g

10 mg 5-FU i.a. + 6 mg Amilomer0 15 30 45 60 90 2 h4 h 8 h12 h24 h0

100

200

300

400

500

600

700

µg

/g 5

-FU

Tumor

Liver

433.39 µg/g

664.39 µg/g

5-FU-CONCENTTRATION IN TUMOR AND LIVER(locoregional with and without amilomer)

Chirurgische Klinik I Universitätsklinikum Benjamin Franklin FU Berlin

7

PHARMACOKINETIC WITH DE BEADS:TUMOR DOXORUBICIN CONCENTRATION

Hong K, et al. Clin Cancer Res 2006;12:2563–7, Courtesy: R. Lencioni, Pisa

Dox

oru

bic

in in t

um

or

(nm

ole

s/g)

450

400

350

300

250

200

150

100

50

0

Time from doxorubicin administration (hours)

0 100 200 300 400

HAI

DE Beads

8

0 15 30 45 60 90 2 h 4 h 8 h 12 h 24 h0

100

200

300

400

500

600

700

µg/g

5-F

U

+ 30 x

Time from doxorubicin administration (hours)

Dox

oru

bic

in in

tu

mor

(nm

ole

s/g

)

450

400

350

300

250

200

150

100

50

0

0 100 200 300 400

TACE

DE Beads

0 15 30 45 60 90 2 h 4 h 8 h 12 h 24 h0

100

200

300

400

500

600

700

5-FU + DSM

µg/g

5-F

U

+ 30 x

5-FU-concentration in tumor and liver (locoregional with and without Amilomer)

AUC ?+ 3 x

EMBOCEPT S VS. BEADSPK DATA

9

TUMOR GROWTH AND NECROSIS

Dt. Krebskongress Berlin2014

10

DSM (EMBOCEPT® S) VS. DC BEADS

pharmacokinetics

clinics

therapeutic/technical recommendation

11

DSM – CLINICAL DATA

Taguchi et al. Reg Cancer Treatment 3-4:117 1992

clinics (TACE)

Taguchi, T. (1992): random. phase III - study

indications: 1) HCC (n=60)2) liver metastases (n=60)

12

DSM – CLINICAL DATA

Taguchi et al. Reg Cancer Treatment 3-4:117 1992

clinics (TACE)

Taguchi, T. results (HCC)

*) p<0,05

DSM CR PR CR+PR* (%)

MR NC PD Mediansurvival*

(days)

With 2 6 36,4 4 10 0 661

without

0 2 9,5 1 11 7 259

13

DC BEADS – CLINICAL DATA

14

PRECISION V

Event DC beads(N=93)

Lipiodol TACE(N=108)

Lipiodol TACE

(N=263)

DSM-TACE(N=98)

PES (pain)

25 26 23 2

Nausea 16 14 15 3

Vomiting 11 13 10 4

Pyrexia 17 24 17 3

Bonn data

DC BEADS VS. DSM-TACE – TOLERABILITY

Vogl et al. AJR 197 2011, Schlee et al. 1999

15

C-TACE VS. DSM-TACE – TOLERABILITY

Schlee et al. 1999

16

Thomas Albrecht, Julian Wirsching, Gerd Berger

Institut für Radiologie und Interventionelle TherapieVivantes-Klinikum Neukölln, Berlin

Charité, Campus BF, Berlin

thomas.albrecht@vivantes.de

Sequence of repeated non-selective non-occlusive TACE of far advanced HCC with degradable starch microspheres (DSM) –

long term results of a retrospective analysis

17

DSM (EMBOCEPT® S) VS. DC BEADS

pharmacokinetics

clinics

therapeutic/technical recommendation

18

HANDLING OF DC BEADS

19

HANDLING OF DSMapplication modus 1

20

HANDLING OF DSMapplication modus 2

21

HANDLING OF DSMapplication modus 3

22

 

DC beads® EmboCept® S

Vials 2x2 1

Preparation time app. 24 h app. 5 min.

Catheter positioning (super-) selective

non-selective (incl. IA ports)

Micro-catheter X -

Additional embol. material(e.g. Bead block) X -

DSM (EMBOCEPT® S) VS. DC BEADSapplication modus

23

Indication(liver mets)

Active substances in combination

Cycles

Pancreatic Ca Gemcitabin, Mitomycin C

every 3-4 weeks

CRC Irinotecan, Oxaliplatin, Mitomycin C

every 3-4 weeks

Neuroendocrine Tm Doxorubicin, Mitomycin C

every 3-4 weeks

Breast Ca Gemcitabin,Mitomycin C,Taxanes

every 3-4 weeks

Melanoma Fotemustine,cisDDP

every 3-4 weeks

DSM-TACE –indications and schedules

24

DSM (EMBOCEPT® S) IN COMPARISON

EmboCept® Svs. DC BeadsPharmacokineticsClinicsTherapeutic/technical recommendationvs. lipiodol

25

CHEMOEMBOLIZATION – LIPIODOL ® + / - DSM

26

60-80 mg cisplatin +

Lipiodol(4.8+/-2 mL) DSM 120-3000 mg Lipiodol 4.1+/-2 mL + (+CM) DSM 427+/-405 mg +

CM (until stasis)

CHEMOEMBOLIZATION – LIPIODOL® + / - DSM

Yamasaki T et al. J Gastroenterol (2011) 46: 359-66

Randomization

27

1y 2y 3y

Lipiodol-group: 13 % 13 %

DSM-group: 27 %

Lipiodol+DSM-group:53 % 13 % 7 %p=0.02/0.035

CHEMOEMBOLIZATION – LIPIODOL® + / - DSM

Yamasaki T et al. J Gastroenterol (2011) 46: 359-66

Results 2(progression-free survival):

28

TRANSARTERIAL CHEMOEMBOLIZATION (TACE)

Institut of Diagnostic and Interventional RadiologyJohann Wolfgang Goethe-University, Frankfurt am Main

of hepatocellular carcinoma (HCC):

Comparison of tumor response rates between c(lipiodol)-TACE and DSM-TACE plus lipiodol

 Gruber-Rouh T, Nagy N, Eichler K, Lehnert T, Harth M, Zangos S, Beeres M,

Nour-Eldin NE, Vogl TJ

29

PURPOSE

Evaluation and comparison of local tumor response

under transarterial chemoembolization (TACE) of HCC

with lipiodol or lipiodol plus DSM-microspheres

(EmboCept® S)

Institut of Diagnostic and Interventional RadiologyJohann Wolfgang Goethe-University, Frankfurt am Main

30

MATERIAL AND METHODS

Patients: n = 50

Recruitment time: 2010-2012

Median Age: 60,3 years (39-80)

TACE: n = 367 medium: 7,3 treatments/patient (3-15) therapeutic interval:: 4 weeks

Institut of Diagnostic and Interventional RadiologyJohann Wolfgang Goethe-University, Frankfurt am Main

31

MATERIAL AND METHODS

Institut of Diagnostic and Interventional RadiologyJohann Wolfgang Goethe-University, Frankfurt am Main

chemotherapy

Embolization

Mitomycin (n=50)

Lipiodol (n=25)

lipiodol + DSM (n=25)

TACE-protocol:

32

MATERIAL AND METHODS

Evaluation:

Radilogical tumor response: MRT, CT (RECIST-criterias)

Statistical significance:(Wilcoxon-Mann-Whitney-Test)

Institut of Diagnostic and Interventional RadiologyJohann Wolfgang Goethe-University, Frankfurt am Main

33

RESULTS

Amount of liver metastasis: multiple (≥ 5): 50% (n=25) 1: 18% (n=9) 2: 16% (n=8) 3-4: 16% (n=8)

Location of the metastasis: both sides: 70% (n=35) Right lobe: 30% (n=15) left lobe: 0% (n=0)

Institut of Diagnostic and Interventional RadiologyJohann Wolfgang Goethe-University, Frankfurt am Main

34

RESULTS

Local tumor control (RECIST- criterias):

Institut of Diagnostic and Interventional RadiologyJohann Wolfgang Goethe-University, Frankfurt am Main

PR26%

SD60%

PD14%

►partial response (PR): 26 % (n=13)

►stable disease (SD): 60 % (n=30)

►progressive disease (PD): 14 % (n=7)

35

RESULTS

Institut of Diagnostic and Interventional RadiologyJohann Wolfgang Goethe-University, Frankfurt am Main

Lipiodol-group DSM-lipiodol-

group

Tumor response(PR + SD)

80% (n=20)

92% (n=23)p =

0,32

36

SUMMARY 1/4

DSM – TACE: highest accumulation of co-applicated drugs within the tumor tissue

EmboCept® S (DSM 35/50) – short-time embolization:

• no initiation signals for collateral tumor vessel• comparable high tumor necrosis

37

SUMMARY 2/4

DSM-TACE comparable to DEB-TACE in tumor response, but better in tolerability

DSM-TACE better than c-TACE

38

SUMMARY 3/4

DSM-TACE: options for new scientific concepts

combination with:• LITT/RF,• Radiation / SIRT• immune-/ genembolization

39

SUMMARY 4/4

EmboCept® S: unique chemoembolization material

• combination

• indication

• application