Drug Eluting Beads for TACE

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Drug Eluting Beads for TACE

• T de Baere
• Institut Gustave Roussy, Villejuif

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Clinical results of Drug eluting beads -
Rational - HCC - NET (neuroendocrine tumors)
or GEP (gastroanteropancreatic endocrine
tumors) - Colrectal cancer metastases
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Rational
(Pohlen, U et al. J Surg Res 2000 92 165-70)

• High clearance (CL)
• High extraction ratio (Er)
• Er at first pass
• Keep it longer in the liver
• Low blood flow (Qa)
• Embolization

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Pharmakokinetic in animal
Rational
Courtesy of J Geschwind
Courtesy of J Geschwind
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Pharmakokinetic in animal
Rational
Courtesy of J Geschwind
Courtesy of J Geschwind
Pharmakokinetic in human
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Preliminary clinical results
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Difficulties in evaluating Preliminary
clinical results
64
Response rate
Varela M, Llovet J, Bruix J, J Hepatol
2007
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Difficulties in evaluating Preliminary
clinical results
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35-37
44
EASL
RECIST
Lo C, Hepatology 2002 Llovet JM, Lancet
2002 Varela M, Llovet J, Bruix J, J Hepatol
2007
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Difficulties in evaluating Preliminary
clinical results
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• 71 patients
• HCC (3-10cm)
• Child A (27), Child B (44)
• EASL (intention to treat)
• CR 15.5
• OR 66.2 to 85.5 across the 4 treatments

(Malagari K, Abdominal imaging 2007)
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• 71 patients
• HCC (3-10cm)
• Child A (27), Child B (44)
• EASL (intention to treat)
• CR 15.5
• OR 66.2 to 85.5 across the 4 treatments

Best Overall response 53/71 74
(Malagari K, Abdominal imaging 2007)
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• 71 patients
• HCC (3-10cm)
• Child A (27), Child B (44)
• EASL (intention to treat)
• CR 15.5
• OR 66.2 to 85.5 across the 4 treatments
• Survival
• 97.5 _at_ 12 months
• 91.1 _at_ 18 months
• 88.2 _at_ 30 months

(Malagari K, Abdominal imaging 2007)
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4ml of 300-500 mm DEB 100 mg doxorubicin

• Neuroendocrine liver metastases
• Morphologic RECIST _at_ 1 months
• Partial response 8/20 (40)
• Minor response 2/20 (10)
• Stable disease 5/20 (25)
• Progressive disease 1/20 (5)

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4ml of 300-500 mm DEB 100 mg doxorubicin

• Neuroendocrine liver metastases
• Morphologic RECIST _at_ 1 months - 3 months
• Partial response 8/20 (40) - 16/20 (80)
• Minor response 2/20 (10) - 2/20 (10)
• Stable disease 5/20 (25) - 1/20 (5)
• Progressive disease 1/20 (5) - 1/20 (5)

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DEB preliminary results
4ml of 300-500 mm DEB 100 mg doxorubicin

• Neuroendocrine liver metastases
• Morphologic RECIST _at_ 1 months - 3 months
• Partial response 8/20 (40) - 16/20 (80)
• Minor response 2/20 (10) - 2/20 (10)
• Stable disease 5/20 (25) - 1/20 (5)
• Progressive disease 1/20 (5) - 1/20 (5)
• 20 peripheral liver necrosis associate with more
  post-procedural pain

(In press, JVIR)
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DEB preliminary results
4ml of 300-500 mm DEB 100 mg doxorubicin

• Neuroendocrine liver metastases
• Morphologic RECIST _at_ 1 months - 3 months
• Partial response 8/20 (40) - 16/20 (80)
• Minor response 2/20 (10) - 2/20 (10)
• Stable disease 5/20 (25) - 1/20 (5)
• Progressive disease 1/20 (5) - 1/20 (5)

Lipiodol TACE PR 41 MR 33 SD 15 (A
Roche T de Baere Europ Radiol 2003)
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Irinotecan DEBProof-of-Concept Study Design

• Evaluation of TACE in a rat liver metastasis
  model
• Model Diffuse liver metastasis is induced by
  injecting 4x106 CC531-lac-Z rat colorectal
  carcinoma cells into the portal vein of male
  Wag/Rij rats
• Objectives
• Compare embolization only to Irinotecan (low and
  high dose)
• Doses chosen 20 mg/kg and 30 mg/kg Irinotecan
• Determine the effectiveness in terms
• reduction in tumor cell load
• liver weight

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Irinotecan DEB Proof-of-Concept Study
Preliminary Data

• Preliminary results presented at AACR
  (Washington, April 06)

p0.07
p0.05
DC Bead
Irinotecan 20mg/kgDEB
Irinotecan 30mg/kgDEB
Embolizqtion
No Drug
Chemoemebolization of rat colorectal liver
metastases with drug eluting beads loaded with
irinotecan or doxorubicin. Clin Exp Metastasi
2008. Eyol E et al
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DC beads and colorectal metastases

• 62 patients with CRC metastases
• At least 2 previous lines of chemotherapy
• Tumor burden lt 70
• Bilirubin w X2 normal value
• 138 courses of TACE with Irinotecan-DEB
• 2ml DEB 100-300 2ml 300-500 / 200 mg
  irinotecan
• 1-3 courses TACE every 3/4 weeks
• 55 right, 47 left, 39 rightleft
• 48 X 2ml 90 X 4ml

(Aliberti C, Fiorentini G, Cancer Research 2006)
(Aliberti C, Fiorentini G, CIRSE 2008)
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DC beads and colorectal metastases

• 62 patients with CRC metastases
• Med Follow-up 15.4 months
• Response
• EASL 85
• RECIST 78 _at_ 3 months
• Improvement of QOL 90 during 3-12 months
  (med 6.5)
• Survival
• Median survival not reached at 22 months
• Median free of symptioms 5.3 months
• Median to new chemo 6.3 months

(Aliberti C, Fiorentini G, Cancer Research 2006)
(Aliberti C, Fiorentini G, CIRSE 2008)
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Combined treatment
CT immediately post DEB injection
CT at 6 weeks
Angiogram Post RF of colorectal mets
(R Lencioni, J Hepatology 2008)
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DEB future

• Randomization DEB / Conventional
• Precision V in Europe (completed)
• MRI at 3m and 6m
• Efficacy (treatment response).
• European Association for the Study of the Liver
  (EASL)
• Response Evaluation Criteria in Solid Tumours
  (RECIST)
• SURVIVAL ?
• Colo-rectal cancer
• Hudge population, numerous drugs in 1st to 3rd
  lines

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Drug Eluting Beads

• Reproducibility gt Lipiodol
• Low systemic level drug
• Increase in efficacy
• Decrease toxicity
• Encouraging preliminary results
• combination with so called targeted therapy ?
• sorafenib, sunitinib,