Download DC Bead® with irinotecan Offering the benefits of DC Bead to more

DEBIRI* for Metastatic
Colorectal Cancer
* Drug-Eluting Bead Irinotecan
DC Bead® with irinotecan
Offering the benefits of DC Bead
to more patients
DC Bead® with irinotecan
Offering the benefits of DC Bead
to more patients
DC Bead is a Drug Delivery Embolisation System capable of loading and
releasing in a controlled manner high doses of chemotherapeutic agents.
†
DC Bead Presentation
• Novel N-fil technology sulphonate modified hydrogel polymer
• Blue tinted to aid visualisation
• Delivered as vials containing 2ml Beads in 6ml saline
• Precise calibration to achieve an accurate level of embolisation
“My experience in using DEBIRI to treat more than 80 patients, with in excess of 180 procedures, shows that
DEBIRI is an effective treatment option for patients with refractory metastatic colorectal disease. The lack of
major complications with good control of post-embolisation syndrome gives DEBIRI a favourable safety profile”
Camillo Aliberti, Professor of Interventional Radiology
Delta Hospital Lagosanto, Ferrara, Italy
DC Bead Irinotecan Mode of Loading
Irinotecan Mode of Action
Hydrated Beads
Irinotecan is enzymatically cleaved in the body to the active metabolite SN-38
Grafting point
PVA macromer
backbone
-
SO3
3
SO
Sulphonated polymer
chain backbone
-
SO3
Irinotecan and its active metabolite SN-38 bind to the topoisomerase
I-DNA complex and prevent religation of these single-strand breaks
-
SO3
3
SO
SO
-
SO3
3
-
SO3
-
SO3
Hydration shell
associated with PVA
and ionic groups
This inhibits Topoisomerase I which relieves torsional strain in DNA by
inducing reversible single-strand breaks.
-
SO3
-
SO3
O
-
SO3
N
Bulk
(non-bound) water
3
SO
N
C
O
O
N
Irinotecan Solution
N
Drug-loaded Beads
O
Irinotecan
H2O
Irt
O
OH
SO3
Irt
Interaction of irinotecan (Irt)
with SO3- groups by an
ion-exchange process
displaces water from
the hydration shells
Irt
SO3
SO3
Irt
SO3
Irt
SO3
Irt
Irt
Instructions For Use.
SO3
SO3
Irt
SO3
SO3
† Biocompatibles
SO3
O
Irt
Irt
Irt
SO3
Irt
SO3
Irt
SO3
N
N
C
OH
HO
O
N
N
O
SN-38
O
OH
“After more than 3 years experience with DC Bead, we are now giving 200mg of irinotecan and a
solution of 2-4ml of 100-300µm and/or 300-500µm microspheres mixed with non-ionic contrast
medium. This solution is injected into the artery. Our results show that DEBIRI is effective in the
control of colorectal liver metastases recalcitrant to first and second-line chemotherapy”
Giammaria Fiorentini, Professor of Medical Oncology
General Hospital Nuovo San Giuseppe, Empoli (Florence), Italy
DEBIRI ALGORITHM – Colorectal Metastases
Note: These notes are for guidance only and should not be seen as a recommendation or used in isolation to make clinical decisions that relate to patient care or medication
1. Initial scanning assessment:
Use 3 Phase CT +/- PET scan (if available) to confirm the extent
of the disease and whether the disease is liver dominant – defined
as the extent of liver involvement being greater than 80% of
the overall tumour burden. If <80%, then the large amount of
extrahepatic disease may pose a greater risk of mortality than
that contained within the liver, and the benefits of liver-directed
therapy must be carefully reconsidered.
• Position the catheter in the right or left hepatic artery depending
on the lobe to be treated.
2. Define amount of liver replacement:
Unilobar or Bilobar and up to 60% of the liver replaced by
tumour or greater than 60% liver replacement.*
• Give a slow injection of loaded DC Bead in 1ml aliquots followed
by saline over an approx 3-5 minute period.
a. Unilobar disease and up to 60% liver replacement:
Plan two treatments, each of them with a maximum of 100mg
irinotecan loaded in one 100-300µm DC Bead vial,
separated by four weeks.
b. Bilobar disease and up to 60% liver replacement:
Plan four lobar treatments each of them with one vial of
100-300µm DC Bead loaded with 100mg irinotecan every
two weeks (treat alternate lobes – first treatment right lobe,
wait two weeks and then treat the left lobe. Two weeks later,
perform a second treatment of the right lobe, wait two weeks and
then a second treatment of the left lobe. Repeat scan
three months from FIRST dose. Patients should be closely
monitored for signs and symptoms of hepatic and systemic
toxicity, and consideration given to extending the intervals
between treatments as necessary.
* In case of greater than 60% liver replaced by tumour,
chemoembolisation treatment is not recommended
• Identify the cystic artery and that the catheter tip is placed past
the cystic artery prior to injecting DC Bead.
• Remove excess irinotecan solution from the vial of irinotecanloaded DC Bead. Mix the loaded DC Bead with non-ionic contrast
media as per the instructions for use.
• Inject sufficient loaded DC Bead to the point where either
the desired dose is injected or near stasis is achieved. The
injection of additional embolic is not required.
4. Response – use modified RECIST or PET response:
• If less than 80% objective response is observed, estimate
the location and amount of residual disease and repeat the
treatment based on this observation. If extrahepatic progression
is observed/detected, collaboration with medical oncologist is
required to decide next treatment steps and whether continued
DEBIRI treatment alone, DEBIRI in combination with systemic
therapy or systemic therapy alone is required.
• If greater than 80% objective response is observed, then
repeat CT or CT-PET every 3-4 months for the first year and every
six months in the second year. If progress occurs in the liver,
evaluate location and extent of liver involved and re-treat
as above. If extrahepatic progression is observed/detected,
collaboration with medical oncologist is required to decide
next treatment steps and whether continued DEBIRI treatment
alone, DEBIRI in combination with systemic therapy or
systemic therapy alone is required.
3. Chemoembolisation procedure:
• Peri-procedural medication:
- Pain management protocol should include a major opioid (eg
morphine) plus intra-arterial lidocaine (1% without adrenaline)
injection 2-4ml prior to DC Bead injection.
5. Additional medications:
• Certain patients have demonstrated hypertension after DEBIRI.
Some investigators have found enalapril (IV 1.25mg or 2.5mg) has
been effective in its management.
- Antibiotic prophylaxis and all other peri-procedural medication
(including anti-emetics) will be according to standard practice for
a liver metastases chemoembolisation procedure.
• Repeat treatment with DC Bead may lead to more severe
nausea and a more aggressive anti-emetic therapy is
recommended.
“Critically, metastatic patients need to be approached for hepatic arterial therapy differently
from those with HCC. Specifically my experience with DEBIRI would indicate that to
optimise the therapy and ensure best practice patient management:
1. Include the use of intra-arterial lidocaine 2-4ml 1% prior to bead delivery as part of the pain management protocol
2. Plan for at least 2 treatments to appropriately assess response
3. To evaluate clinically relevant response, response should be assessed at least one month after treatment
4. Dynamic response criteria - EASL or PET should be utilised to assess response to therapy”
Robert Martin, Associate Professor of Surgery
Division of Surgical Oncology
University of Louisville. Kentucky, USA
DEBIRI ALGORITHM – Colorectal Metastases
Note: These notes are for guidance only and should not be seen as a recommendation or used in isolation to make clinical decisions that relate to patients care or medication.
Patient with liver predominant metastases from colorectal cancer
Yes
Unilobar Disease
Lobar DEBIRI
100mg irinotecan in one
100-300µm vial
No
Bilobar Disease
Lobar DEBIRI in most affected lobe
100mg irinotecan in one
100-300µm vial
2 weeks
Second lobe DEBIRI
100mg irinotecan in one
100-300µm vial
4 weeks
2 weeks
DEBIRI first lobe
100mg irinotecan in one
100-300µm vial
2 weeks
Lobar DEBIRI
100mg irinotecan in one
100-300µm vial
DEBIRI second lobe
100mg irinotecan in one
100-300µm vial
3 months tumour response, then every 3-4 months
for 1 year, then every 6 months for second year
Tumour response <80%
Extrahepatic progression?
No
Yes
Repeat treatment
whenever residual
tumour is found
Other
treatment
options
Tumour
response >80%
Imaging
follow
up
“Currently available data suggest that patients with metastatic colorectal cancer may benefit from
the addition of Drug-Eluting Bead irinotecan (DEBIRI) to their standard systemic chemotherapy.”
Robert Martin, Associate Professor of Surgery
Division of Surgical Oncology, University of Louisville. Kentucky, USA
“From a Medical Oncologist’s perspective, I consider DEBIRI to be a valid treatment option for my patients
with metastatic colorectal disease who have failed first-line systemic chemotherapy. DEBIRI could bring
some hope to these patients whose response to systemic chemotherapy is very low.”
Giammaria Fiorentini, Professor of Medical Oncology
General Hospital Nuovo San Giuseppe, Empoli (Florence), Italy
Surgical downstaging and neoadjuvant therapy in metastatic colorectal carcinoma with
Drug-Eluting Bead irinotecan (DEBIRI)
• Disease control, defined as complete response (CR), partial response (PR) and stable disease (SD),
was seen in 89% of patients at 3 months, 80% at 6 months, 88% at 12 months.
• Eleven patients (20%) were downstaged to resection or ablation.
• DEBIRI is safe and shows potential efficacy in downstaging patients with unresectable colorectal metastases of the liver.
Tumour Response (RECIST)
3 Months
6 Months
12 Months
18 Months
Complete Response
6%
7%
6%
8%
Partial Response
33%
35%
50%
83%
Stable Disease
52%
54%
32%
0%
Progressive Disease
9%
4%
12%
8%
Source: Dr Matthew Bower, University of Louisville, USA. Oral Presentation American Hepato-Pancreato-Biliary Association Annual Meeting, Miami, Florida, USA. March 14th 2009
Hepatic intra-arterial injection of irinotecan Drug-Eluting Beads in unresectable colorectal
liver metastases refractory to standard systemic chemotherapy
• Systemic chemotherapy for unresectable metastatic colorectal cancer (MCC) is the optimal initial management
of these patients. However, after a patient has failed first-line and in some case second-line chemotherapy, the
response rates fall to as low as 12%. The aim of this study was to evaluate the efficacy of precision hepatic
arterial irinotecan therapy in MCC patients who have failed first-line and/or second-line chemotherapy.
• Hepatic arterial infusion with irinotecan was safe and effective in the treatment of MCC refractory to multiple
lines of systemic chemotherapy.
Total N = 55
Prior Therapy
#
Patients
Median # DEBIRI
Treatments (Range)
Median Total Dose
Irinotecan (Range)
SAE
Tumour Response
(EASL)
FOLFOX + Avastin
17
2 (1-3)
200 (50-600)
1 (6%)
Grade 3
75% 3 Months
55% 6 Months
60% 12 Months
FOLFOX + Avastin &
FOLFIRI + Eribitux
14
2 (1-4)
200 (50-450)
1 (7%) Grade 3
1 (7%)
Grade 5
80% 3 Months
70% 6 Months
75% 12 Months
FOLFOX + Avastin &
FOLFIRI + Eribitux &
Xelox + Vectibex
Other
24
2 (1-5)
200 (50-600)
2 (8%) Grade 3
1 (4%)
Grade 5
50% 3 Months
60% 6 Months
75% 12 Months
Source: Dr Robert Martin, University of Louisville, USA. Abstract, ASCO Gastrointestinal Cancers Symposium, San Francisco, California, USA. January 15-17th 2009
Loading of DC Bead® Using Irinotecan DC Bead should be prepared under aseptic conditions
1ml of DC Bead absorbs up to 50mg of irinotecan
Step 1
Step 3
Remove as much saline as possible
from DC Bead vial(s). using a syringe with
a small gauge needle. Pierce bung with
a second needle to eliminate vacuum.
During the 2-hour loading
period, agitate the beads
occasionally. This will help
ensure effective loading.
A change in the bead colour
from blue to turquoise will
be observed.
If a filter needle is not available,
place flattened tip of needle
against side of vial to
prevent beads
being drawn
up the needle.
Step 4
At the end of the loading time,
remove excess solution from
the vial and discard.
Label
Colour
Nominal
Bead Size
Loading
Time
Product
Code
Yellow
100-300µm
2 hours
DC2V103
Step 2
Using a syringe and needle add the appropriate
volume of irinotecan solution to the DC Bead
vial(s) to give the desired dose and total
DC Bead volume.
Step 5
Prior to use, add 5ml of water for
injection and 5ml of non-ionic
contrast medium to the vial.
Transfer the contents of the
vial to a syringe. Invert the
syringe gently to obtain an
even suspension of beads.
DC Bead Bibliography
Intraarterial Hepatic
Chemoembolization of Liver
Metastases from colorectal cancer
Adopting Irinotecan-eluting Beads:
Results of a Phase II Clinical Study.
Preservation of the active
lactone form of irinotecan
using drug eluting beads
for the treatment of colorectal
cancer metastases.
Fiorentini, G., Aliberti, C., Turrisi, G. et al
In vivo 21: 1085-1092 (2007)
Tang, Y., Czuczman, P.R., Chung, S.T. et al
Journal of Controlled Release 127 (2008) 70-78
Trans-arterial Chemoembolization
(TACE) of Liver Metastases
from colorectal cancer Using
Irinotecan-Eluting Beads:
Preliminary Results.
Irinotecan drug eluting beads
for use in chemo-embolization:
In vitro and in vivo evaluation
of drug release properties.
Aliberti C., Tilli M., Benea G., Fiorentini G.
Anticancer Research 26:3779-3782 (2006).
Reprinted from Anticancer Research 26, with permission from the Anticancer Research Institute.
DC Bead is a registered trademark of Biocompatibles UK Ltd. DC
Bead® is not currently available for sale or distribution in the USA.
EC09-033(T) © 2009 Biocompatibles UK Ltd.
Chemoembolisation of rat
colorectal liver metastases
with drug eluting beads loaded
with irinotecan or doxorubicin.
Eyol, E., Boleij, A., Taylor, R. et al
Clinical and Experimental Metastasis
(2008) 25: 273-282
Taylor, R.R., Tanga, Y., Gonzalez, M.V. et al.
European Journal of Pharmaceutical Sciences
30 (2007) 7-14.
Reprinted from European Journal of Pharmaceutical Sciences 30, with permission from Elsevier.
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