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
vs. 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 min.
degadation by -amylase
fragments: Dalton (water-soluble)

4. advantages of a degradable material
Chemoembolization –
advantages of a degradable material
Angiographic documentation of vessels
permanent embolization N
collateral tumor vessels
6 h 4
4 h 5 3
2 h
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. 5-fu-concenttration in tumor and liver
(locoregional with and without amilomer) 15 30 45 60
90 Min 10 20 40 50 70
µg/g 5-FU
Tumor
Liver
25,09 µg/g
58,65 µg/g
10 mg 5-FU i.a.
AUC: 10 mg 5-FU i.a.
versus 10 mg 5-FU + 6 mg Amilomer i.a.
655
62655
1704
27822
5-FU i.a.
5-FU+Amilomer i.a.
95 x
60000
50000
40000
AUC ( min) µg/g*min 15 30 45 60 90
2 h
4 h
8 h
12 h
24 h
100
200
300
400
500
600
700
µg/g 5-FU
Tumor
Liver
µg/g
µg/g
20000
10000
10 mg 5-FU i.a mg Amilomer
Chirurgische Klinik I Universitätsklinikum Benjamin Franklin FU Berlin

7. Pharmacokinetic with de beads: Tumor doxorubicin concentration
Doxorubicin in tumor (nmoles/g)
450
400
350
300
250
200
150
100 50
Time from doxorubicin administration (hours)
HAI
DE Beads
Hong K, et al. Clin Cancer Res 2006;12:2563–7, Courtesy: R. Lencioni, Pisa 7

8. AUC ? EmboCept S vs. Beads Pk data 0 100 200 300 400 + 3 x
Doxorubicin in tumor (nmoles/g)
450
400
350
300
250
200
150
100 50
TACE
DE Beads
+ 3 x
AUC ?
Time from doxorubicin administration (hours)
5-FU-concentration in tumor and liver (locoregional with and without Amilomer) 8

9. Tumor growth and necrosis
Dt. Krebskongress Berlin2014

10. Dsm (EmboCept® s) vs. Dc beads
pharmacokinetics
clinics
therapeutic/technical recommendation

11. Dsm – clinical data clinics (TACE) Taguchi, T. (1992):
random. phase III - study
indications: 1) HCC (n=60) 2) liver metastases (n=60)
Taguchi et al. Reg Cancer Treatment 3-4:

12. Dsm – clinical data clinics (TACE) Taguchi, T. results (HCC) DSM CR PRMR NC PD
Median
survival*
(days)
With 2 6
36,4 4 10
661
without
9,5 1 11 7
259
Taguchi et al. Reg Cancer Treatment 3-4:

13. Dc beads – clinical data

14. Dc beads vs. DSM-TACE – tolerability
PRECISION V
Bonn data
Event
DC beads
(N=93)
Lipiodol TACE
(N=108)
(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
Vogl et al. AJR , Schlee et al. 1999

15. c-TACE vs. dsm-tace – tolerability
Schlee et al. 1999

16. long term results of a retrospective analysis
Sequence of repeated non-selective non-occlusive TACE of far advanced HCC with degradable starch microspheres (DSM) –
long term results of a retrospective analysis
Thomas Albrecht, Julian Wirsching, Gerd Berger
Institut für Radiologie und Interventionelle Therapie Vivantes-Klinikum Neukölln, Berlin
Charité, Campus BF, Berlin

17. Dsm (EmboCept® s) vs. Dc beads
pharmacokinetics
clinics
therapeutic/technical recommendation

18. Handling of dc beads

19. Handling of dsm
application modus 1

20. Handling of dsm
application modus 2

21. Handling of dsm
application modus 3

22. non-selective (incl. IA ports)
Dsm (emboCept® S) vs. Dc beads
application modus
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)

23. indications and schedules
Dsm-tace –
indications and schedules
Indication
(liver mets)
Active substances in combination
Cycles
Pancreatic Ca
Gemcitabin, Mitomycin C
every 3-4 weeks
CRC
Irinotecan, Oxaliplatin, Mitomycin C
Neuroendocrine Tm
Doxorubicin, Mitomycin C
Breast Ca
Gemcitabin,
Mitomycin C,
Taxanes
Melanoma
Fotemustine,
cisDDP

24. DSM (Embocept® s) in comparison
vs. DC Beads
Pharmacokinetics
Clinics
Therapeutic/technical recommendation
vs. lipiodol

25. Chemoembolization –
Lipiodol ® + / - dsm

26. Chemoembolization – Lipiodol® + / - DSM Randomization
60-80 mg cisplatin +
Lipiodol(4.8+/-2 mL) DSM mg Lipiodol 4.1+/-2 mL + (+CM) DSM 427+/-405 mg +
CM (until stasis)
Yamasaki T et al. J Gastroenterol (2011) 46:

27. Chemoembolization – Lipiodol® + / - Dsm Results 2
(progression-free survival):
1y 2y 3y
Lipiodol-group: 13 % 13 %
DSM-group: 27 %
Lipiodol+DSM-group: 53 % 13 % 7 %
p=0.02/0.035
Yamasaki T et al. J Gastroenterol (2011) 46:

28. of hepatocellular carcinoma (HCC):
Transarterial chemoembolization (tace)
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
Institut of Diagnostic and Interventional Radiology Johann Wolfgang Goethe-University, Frankfurt am Main

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 Radiology Johann Wolfgang Goethe-University, Frankfurt am Main

30. Material and methods (3-15) Patients: n = 50
Recruitment time:
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 Radiology Johann Wolfgang Goethe-University, Frankfurt am Main

31. Material and methods TACE-protocol: chemotherapy Mitomycin (n=50)
Embolization
Lipiodol (n=25)
lipiodol + DSM (n=25)
Institut of Diagnostic and Interventional Radiology Johann Wolfgang Goethe-University, Frankfurt am Main

32. Material and methods Evaluation:
Radilogical tumor response: MRT, CT (RECIST-criterias)
Statistical significance:
(Wilcoxon-Mann-Whitney-Test)
Institut of Diagnostic and Interventional Radiology Johann Wolfgang Goethe-University, Frankfurt am Main

33. Results Amount of liver metastasis: multiple (≥ 5): 50% (n=25)
Location of the metastasis:
both sides: 70% (n=35)
Right lobe: 30% (n=15)
left lobe: 0% (n=0)
Institut of Diagnostic and Interventional Radiology Johann Wolfgang Goethe-University, Frankfurt am Main

34. Results Local tumor control (RECIST- criterias):
►partial response (PR): 26 % (n=13)
►stable disease (SD): 60 % (n=30)
►progressive disease (PD): 14 % (n=7)
Institut of Diagnostic and Interventional Radiology Johann Wolfgang Goethe-University, Frankfurt am Main

35. Results Tumor response (PR + SD) Lipiodol-group DSM-lipiodol-group
Institut of Diagnostic and Interventional Radiology Johann Wolfgang Goethe-University, Frankfurt am Main

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