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Irinotecan eluting DC Bead® M1 for Treatment of Colorectal Liver Metastases: Preliminary Results Peter Huppert Department of Diagnostic and Interventional.

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Presentation on theme: "Irinotecan eluting DC Bead® M1 for Treatment of Colorectal Liver Metastases: Preliminary Results Peter Huppert Department of Diagnostic and Interventional."— Presentation transcript:

1 Irinotecan eluting DC Bead® M1 for Treatment of Colorectal Liver Metastases: Preliminary Results Peter Huppert Department of Diagnostic and Interventional Radiology Klinikum Darmstadt Academic Teaching Hospital Universities Heidelberg/Mannheim & Frankfurt Germany GEST 2011

2 TACE of Colorectal Cancer Liver Metastases pts. linedrugsembx.ORR(%)PFSV(mo) mOSV (mo) Tellez `98 30 SLC/D/Mcollagen n.r.n.r. 9 Leichman `99 31 FLC/D/Mcollagen 298 14 Salman `02 24 SLFU/INFPVA 21n.r. 11 Müller ´03 66 FSLFU/MelIO/GF 438 8 Hong ´09 21 FSLC/D/MPVA n.r.n.r. 8 Vogl `09 463 SLM/Gem/IIO/DSM 15*n.r. 14 Albert `10 121 SLC/D/MIO/PVA 2*3 9 Drugs: C= Cisplatin; D=Doxorubicin; M=Mitomycin C; FU=5-FU; INF=Interferon; Mel=Melphalan; Gem= Gemcitabin, I=Irinotecan; *RECIST

3 TACE of Colorectal Cancer Liver Metastases pts. linedrugsembx.ORR(%)PFSV(mo) mOSV (mo) Tellez `98 30 SLC/D/Mcollagen n.r.n.r. 9 Leichman `99 31 FLC/D/Mcollagen 298 14 Salman `02 24 SLFU/INFPVA 21n.r. 11 Müller ´03 66 FSLFU/MelIO/GF 438 8 Hong ´09 21 FSLC/D/MPVA n.r.n.r. 8 Vogl `09 463 SLM/Gem/IIO/DSM 15*n.r. 14 Albert `10 121 SLC/D/MIO/PVA 2*3 9 Drugs: C= Cisplatin; D=Doxorubicin; M=Mitomycin C; FU=5-FU; INF=Interferon; Mel=Melphalan; Gem= Gemcitabin, I=Irinotecan; *RECIST -No improvement of local oRR compared to historical HAI studies -No comparative studies to systemic treatment in SL setting T.P. Pwint : „…the role of chemoembolization in liver metastases from CRC has not been established.“ (Semin Oncol 2010;37:149-159) -rationale for Irinotecan eluting Microspheres

4 Rart : advantage of IA vs IV CL : total body clearance QA : arterial flow Er :extraction ratio /1st pass CL R art = Q A (1 - E r ) Regional Advantage of i.a. Irinotecan

5 Rart : advantage of IA vs IV CL : total body clearance QA : arterial flow Er :extraction ratio /1st pass CL R art = Q A (1 - E r ) Regional Advantage of i.a. Irinotecan Drug % Liver extraction Clearance TB (l/min) 5-FU 22-452-5 FUDR 69-925-15 IRINOTECAN 38-729-25 MITO-C 7-183-5 CDDP 8-500.3-0.5 DOXO 45-50-

6 DC Beads + Irinotecan® DC Bead before irinotecan loading DC Bead after irinotecan loading

7 Loading procedure of DEBIRI  1 Vial 2 cc Beads + 6 cc saline  aspirate saline

8 Loading procedure of DEBIRI  1 Vial 2 cc Beads + 6 cc saline  aspirate saline  add 100 mg Irinotecan (5 cc Campto®, Pfizer)

9 Loading procedure of DEBIRI  1 Vial 2 cc Beads + 6 cc saline  aspirate saline  add 100 mg Irinotecan (5 cc Campto®, Pfizer)  loading time 120 min  aspirate excess  add CM (5 cc plus X) and water (X cc)

10 Irinotecan eluting Beads  Precisely calibrated size 70-150 µm 100-300µm 300-500µm  Loading by ion exchange 50 mg I/cc Beads 100 mg / Vial in vitro  Uptake (3h) 93%  Release (1w) 100%  t75% 66 min Jordan et al. 2010 JVIR 21:1084-90 Forni et al Cancer Res. 2008

11 Will Beads enter colorectal cancer metastases?

12

13 Yes! 100 mg Irinotecan loaded in 2 cc Beads 70-150 µm + 5 cc CM

14 Prospective Single Center Single Arm Study Ph I/II Irinotecan eluting DC Beads TACE in CRC-LMts. (1-9 / 2010) Protocol (12 Patients, 31 TACE)  100 mg Irinotecan/ 2cc Beads  35-200 mg (mean: 178 mg) Irinotecan/trx.  sel. injection via 3 F micro-cath. if possible  endpoint: stopflow*  i.v. Kevatril®, Dexam., Morphine, Metamizol  TACE/pt. mean: 2.5, range: 2-3  Trx.interval mean: 4.9 w, range: 2-12 w  study endpoints: response (EASL, RECIST), TTP, overall SV, side effects 100-300 µm

15 Inclusion criteria  Unresectable liver metastases  Progression after standard systemic treatment or intolerable side effects  Approved by the local ethics committee  Patients informed consent

16 Case # 1 DC Beads CR/PR Age/sexLMtsSyst. Trx.TACEIrinotcDEBEASLRECISTSV 58y / f10/0811/05-2/10

17 Case # 1 DC Beads 100-300 µm CR/PR Age/sexLMtsSyst. Trx.TACEIrinotcDEBEASLRECISTSV 58y / f10/0811/05-2/1011.02.10 23.02.10 100 mg 2 cc 2 cc Beads 100-300 µm 100 mg Irinotecan

18 Case # 1 DC Beads 100-300µm CR/PR Age/sexLMtsSyst. Trx.TACEIrinotcDEBEASLRECISTSV 58y / f10/0811/05-2/1011.02.10 23.02.10 100 mg 2 cc PR (70%) PR (3mo) al. 3 months 2 months baseline

19 Results DEBIRI 100-300µm DC BeadsCRPRSDPD 3-Mo EASL23%41%18% 3-Mo RECIST06%71%23% 6-Mo RECIST0043%57% median TTP5 mo Median OSV9 mo PainNausea/vomitingHypertension Grade 1 14%Grade 1 50%22% Grade 2 23%Grade 2 37% Grade 3 35%Grade 3 13% Grade 4 28%Grade 4 0

20 Case # 2 DC Beads 100-300µm Recurrency Age/sexLMtsSyst. Trx.TACEIrinotcDEBEASLRECISTSV 72 Y / m3/074/07-2/1009.03.10 30.03.10 18.05.10 100mg 2.0 cc PR (80% -20%) SD (4 mo) al 22.2.1022.4.109.6.10 no complete necrosis

21 Case # 3 DC Beads 100-300µm Recurrency ++ Age/sexLMtsChthTACEIrinotcHeSphEASLRECISTSV 64 Y / m9/079/07-5/0802/07/08 05/08/08 10/09/08 200 mg 150 mg 200 mg 50mg 38 mg 50mg PD 8 05/06/08 11/09/08 06/10/08 18/12/08

22 Potential Advantages DC Beads® M1 (70-150 µm)  Deep penetration into tumor vascular bed  Shrinking after loading to 65-120 µm  Preventing collateral supply  Complete necrosis

23 DC Beads M1 (70-150 µm) 28/09/10 Age/sexLMtsChthTACEIrinotcM1 BeadsEASLRECISTSV 78 Y / m9/099/0-8/1028/09/10100 mg2cc (70-150 µm) Dyna- perfusion CT hypovascular tumor

24 DC Beads M1 (70-150 µm) 28/09/10 29/09/10 Age/sexLMtsChthTACEIrinotcM1 BeadsEASLRECISTSV 78 Y / m9/099/0-8/1028/09/10100 mg2cc (70-150 µm) 1 cc M1 2 cc M1 During/after TACE

25 DC Beads M1 (70-150 µm) 28/09/10 29/09/10 Age/sexLMtsChthTACEIrinotcM1 BeadsEASLRECISTSV 78 Y / m9/099/0-8/1028/09/10100 mg2cc (70-150 µm) 1 cc M1 2 cc M1 During/after TACE intensive uptake of Beads/CM

26 DC Beads M1 (70-150 µm) Age/sexLMtsChthTACEIrinotcM1 BeadsEASLRECISTSV 78 Y / m9/099/0-8/1028/09/10100 mg2cc (70-150 µm) 10/10 28/09/1029/09/10 01/1010 Intensive uptake of DC Beads® M1: complete necrosis of hypovascular tumor +3d+1d

27 DC Beads M1 (70-150 µm) Age/sexLMtsChthTACEIrinotcM1 BeadsEASLRECISTSV 78 Y / m9/099/0-8/1028/09/10100 mg2cc (70-150 µm) 10/10 28/09/1029/09/10 01/1010 +3d+1d 70-150 µm Beads have the potential of deep penetration into tumor vascular bed inducing complete necrosis even in hypovascular tumors

28 Prospective Single Center Single Arm Study Ph I/II Irinotecan eluting DC Beads M1 TACE in CRC-LMts. Protocol M1 (8 Patients, 18 TACE)  100 mg Irinotecan/ 2cc Beads  80-200 mg (mean: 118 mg) Irinotecan/trx.  sel. injection via 3 F micro-cath. if possible  endpoint: stopflow*  i.v. Kevatril®, Dexam., Morphine, Metamizol  TACE/pt. mean: 2.5, range: 2-3  Trx.interval mean: 6.1 w, range: 2-16 w  study endpoints: uptake of Beads/CM response (EASL, RECIST), TTP, overall SV, side effects 70-150 µm

29 Patients Characteristics Patients8 age50-82 (71) m/f6/2 prior syst. Trx.7/8 prior syst. Irinotecan Trx.7/8 Liver involvement 50%4/2/2 Extrahepatic Mts.4/8 Indication for DEBIRI: PD/side effects6/2

30 Results DEBIRI M1 Uptake of Beads/CM (+1d)grade 0-4 (1.8) Necrosis (%)50%-100% (77%) First response (EASL)CR 4/8; PR 2/8; PD 2/8 Best response (RECIST) @3Mo.SD 6/8; PD 2/8 TTP (median)1mo-5mo (3.0mo) Extrahepatic PD2/8 Side effects grade 1/2/35/2/1 Complications0 grade 3grade 4grade 2grade 1

31 Preliminary comparison Beads 100-300µm vs. 70-150µm M1 Beads 100-300 µmBeads 70-150 µm (M1) Tumor necrosis56%77% first response (EASL)CR 23% / PR 41%CR 50% / PR 25% Side effects grade 1/2/350/37/13%62/25/13%

32 Preliminary Conclusions  High-grade uptake of M1/CM is associated with complete tumor necrosis.

33 Preliminary Conclusions  Low-grade uptake of M1/CM is associated with incomplete necrosis.

34 Preliminary Conclusions  High-grade uptake of M1/CM occurs in metastases with hypervascularization.

35 Preliminary Conclusions  High-grade uptake of M1/CM occurs in metastases with hypervascularization.

36 Preliminary Conclusions  High-grade uptake of M1/CM occurs in metastases with hypervascularization.

37 Preliminary Conclusions  High-grade uptake of M1/CM occurs in metastases with hypervascularization.

38 Preliminary Conclusions  High-grade uptake of M1/CM also occurs in metastases with low- grade vascularization.

39 Preliminary Conclusions  High-grade uptake of M1/CM also occurs in metastases with low- grade vascularization.

40 Preliminary Conclusions  High-grade uptake of M1/CM also occurs in metastases with low- grade vascularization.

41 Preliminary Conclusions  Singular arterial supply of metastases is associated with high- grade uptake of M1/CM. S4

42 Preliminary Conclusions  Singular arterial supply of metastases is associated with high- grade uptake of M1/CM. S4

43 Preliminary Conclusions  Multiple arterial supply of metastases is associated with low- grade uptake of M1/CM.

44 Preliminary Conclusions  Multiple arterial supply of metastases is associated with low- grade uptake of M1/CM.

45 Preliminary Conclusions  Multiple arterial supply of metastases is associated with low- grade uptake of M1/CM.

46 Preliminary Conclusions  Multiple arterial supply of metastases is associated with low- grade uptake of M1/CM.

47 Preliminary Conclusions  Multiple arterial supply of metastases is associated with low- grade uptake of M1/CM. S4 multiple feeders

48 Preliminary Conclusions  Preliminary results are encuraging in terms of uptake of Beads® and local tumor response.  Treatment intervals are shorter compared to TACE in HCC.  Median TTP in a salvage situation was 3.0 months.  No complications, tolerable side effects.  Continuation of the studies necessary.

49 Drug eluting Microspheres in CRC Mts.- Questions to answer:  Selective vs. non-selective TACE?  Optimal treatment interval 2…..6 weeks?  Combination with systemic biological Trx. (activation of VEGF and HIF-1)

50 Thank You for Your Attention!

51 Mark your calendar! Submit your abstracts by February 11, 2011!


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