To develop a novel endovascular chemotherapy filter (CF) able to remove excess drug from the blood during intra-arterial chemotherapy delivery (IAC), thus preventing systemic toxicities and thereby enabling higher dose IAC. A flow circuit containing 2.5 mL of ion-exchange resin was constructed. Phosphate-buffered saline (PBS) containing 50 mg doxorubicin (Dox) was placed in the flow model with the hypothesis that doxorubicin would bind rapidly to resin. To simulate IAC, 50 mg of doxorubicin was infused over 10 min into the flow model containing resin. Similar testing was repeated with porcine serum. Doxorubicin concentrations were measured over 60 min and compared to controls (without resin). Single-pass experiments were also performed. Based on these experiments, an 18F CF was constructed with resin in its tip. In a pilot porcine study, the device was deployed under fluoroscopy. A control hepatic doxorubicin IAC model (no CF placed) was developed in another animal. A second CF device was created with a resin membrane and tested in the infrarenal inferior vena cava (IVC) of a swine. In the PBS model, resin bound 76% of doxorubicin in 10 min, and 92% in 30 min (P<0.001). During IAC simulation, 64% of doxorubicin bound in 10 min and 96% in 60 min (P<0.001). On average, 51% of doxorubicin concentration was reduced during each pass in single pass studies. In porcine serum, 52% of doxorubicin bound in 10 min, and 80% in 30 min (P<0.05). CF device placement and administration of IAC were successful in three animals. No clot was present on the resin within the CF following the in vivo study. The infrarenal IVC swine study demonstrated promising results with up to 85% reduction in peak concentration by the CF device. An endovascular CF device was developed and shown feasible in vitro. An in vivo model was established with promising results supporting high-capacity rapid doxorubicin filtration from the blood that can be further evaluated in future studies.

References

References
1.
Altekruse
,
S. F.
,
McGlynn
,
K. A.
, and
Reichman
,
M. E.
,
2009
, “
Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005
,”
J. Clin. Oncol.
,
27
(9), pp.
1485
1491
.10.1200/JCO.2008.20.7753
2.
Roche
,
A.
,
Girish
,
B. V.
,
de Baère
,
T.
,
Baudin
,
E.
,
Boige
,
V.
,
Elias
,
D.
,
Lasser
,
P.
,
Schlumberger
,
M.
,
and Ducreux
,
M.
,
2003
, “
Trans-Catheter Arterial Chemoembolization as First-Line Treatment for Hepatic Metastases From Endocrine Tumors
,”
Eur. Radiol.
,
13
(1), pp.
136
140
.
3.
Stuart
,
K.
,
2003
, “
Chemoembolization in the Management of Liver Tumors
,”
Oncologist
,
8
(5), pp.
425
437
.10.1634/theoncologist.8-5-425
4.
Llovet
,
J. M.
,
Real
,
M. I.
,
Montaña
,
X.
,
Planas
,
R.
,
Coll
,
S.
,
Aponte
,
J.
,
Ayuso
,
C.
,
Sala
,
M.
,
Muchart
,
J.
,
Solà
,
R.
,
Rodés
,
J.
,
Bruix
,
J.
, and the Barcelona Liver Cancer Group,
2002
, “
Arterial Embolisation or Chemoembolisation Versus Symptomatic Treatment in Patients With Unresectable Hepatocellular Carcinoma: A Randomised Controlled Trial
,”
Lancet
,
359
(9319), pp.
1734
1739
.10.1016/S0140-6736(02)08649-X
5.
Hwu
,
W. J.
,
Salem
,
R. R.
,
Pollak
,
J.
,
Rosenblatt
,
M.
,
D'Andrea
,
E.
,
Leffert
,
J. J.
,
Faraone
,
S.
,
Marsh
,
J. C.
,
and Pizzorno
,
G.
, “
A Clinical-Pharmacological Evaluation of Percutaneous Isolated Hepatic Infusion of Doxorubicin in Patients With Unresectable Liver Tumors
,”
Oncol. Res.
,
11
(11-12), pp.
529
537
.
6.
Buijs
,
M.
,
Vossen
,
J. A.
,
Frangakis
,
C.
,
Hong
,
K.
,
Georgiades
,
C. S.
,
Chen
,
Y.
,
Liapi
,
E.
,
and Geschwind
,
J. F.
,
2008
, “
Nonresectable Hepatocellular Carcinoma: Long-Term Toxicity in Patients Treated With Transarterial Chemoembolization—Single-Center Experience
,”
Radiology
,
249
(1), pp.
346
354
.10.1148/radiol.2483071902
7.
Curley, S, A., Newmanm, R, A., Dougherty
,
T. B.
,
Fuhrman
,
G. M.
,
Stone
,
D. L.
,
Mikolajek
,
J. A.
,
Guercio
,
S.
,
Guercio
,
A.
,
Carrasco
,
C. H.
,
and Kuo
,
M. T.
,
1994
, “
Complete Hepatic Venous Isolation and Extracorporeal Chemofiltration as Treatment for Human Hepatocellular Carcinoma: A Phase I Study
,”
Ann. Surg. Oncol.
,
1
(5), pp.
389
399
.10.1007/BF02303811
8.
August
,
D. A.
,
Verma
,
N.
,
Vaerten
,
M. A.
,
Shah
,
R.
,
Andrews
,
J. C.
, and
Brenner
,
D. E.
,
1995
, “
Pharmacokinetic Evaluation of Percutaneous Hepatic Venous Isolation for Administration of Regional Chemotherapy
,”
Surg. Oncol.
,
4
(4), pp.
205
216
.10.1016/S0960-7404(10)80037-4
9.
Ku
,
Y.
,
Tominaga
,
M.
,
Iwasaki
,
T.
,
Fukumoto
,
T.
,
Muramatsu
,
S.
,
Kusunoki
,
N.
,
Sugimoto
,
T.
,
Suzuki
,
Y.
,
Kuroda
,
Y.
,
and Saitoh
,
Y.
,
1998
, “
Efficacy of Repeated Percutaneous Isolated Liver Chemoperfusion in Local Control of Unresectable Hepatocellular Carcinoma
,”
Hepatogastroenterology
,
45
(24), pp.
1961
1965
.
10.
Ku
,
Y.
,
Iwasaki
,
T.
,
Fukumoto
,
T.
,
Tominaga
,
M.
,
Muramatsu
,
S.
,
Kusunoki
,
N.
,
Sugimoto
,
T.
,
Suzuki
,
Y.
,
Kuroda
,
Y.
,
Saitoh
,
Y.
,
Sako
,
M.
,
Matsumoto
,
S.
,
Hirota
,
S.
,
and Obara
,
H.
,
1998
, “
Induction of Long-Term Remission in Advanced Hepatocellular Carcinoma With Percutaneous Isolated Liver Chemoperfusion
,”
Ann. Surg.
,
227
(4), pp.
519
526
.10.1097/00000658-199804000-00012
11.
Ku
,
Y.
,
Iwasaki
,
T.
,
Fukumoto
,
T.
,
Tominaga
,
M.
,
Muramatsu
,
S.
,
Kusunoki
,
N.
,
Sugimoto
,
T.
,
Suzuki
,
Y.
,
Kuroda
,
Y.
,
and Saitoh
,
Y.
,
1998
, “
Percutaneous Isolated Liver Chemoperfusion for Treatment of Unresectable Malignant Liver Tumors: Technique, Pharmacokinetics, Clinical Results
,”
Recent Results Cancer Res.
,
147
, pp.
67
82
.10.1007/978-3-642-80460-1
12.
Ravikumar
,
T. S.
,
Pizzorno
,
G.
,
Bodden
,
W.
,
Marsh
,
J.
,
Strair
,
R.
,
Pollack
,
J.
,
Hendler
,
R.
,
Hanna
,
J.
,
and D'Andrea
,
E.
,
1994
, “
Percutaneous Hepatic Vein Isolation and High-Dose Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Tumors
,”
J. Clin. Oncol.
,
12
(12), pp.
2723
2736
.
13.
Ku
,
Y.
,
Tominaga
,
M.
,
Iwasaki
,
T.
,
Fukumoto
,
T.
, and
Kuroda
,
Y.
,
2002
, “
Isolated Hepatic Perfusion Chemotherapy for Unresectable Malignant Hepatic Tumors
,”
Int. J. Clin. Oncol.
,
7
(2), pp.
82
90
.
14.
Porrata
,
L. F.
, and
Adjei
,
A. A.
,
2001
, “
The Pharmacologic Basis of High Dose Chemotherapy With Haematopoietic Stem Cell Support for Solid Tumours
,”
Br. J. Cancer
,
85
, pp.
484
489
.10.1054/bjoc.2001.1970
15.
Skipper
,
H. E.
,
Schabel
,
F. M.
, Jr.,
Mellett
,
L. B.
,
Montgomery
,
J. A.
,
Wilkoff
,
L. J.
,
Lloyd
,
H. H.
,
and Brockman
,
R. W.
,
1970
, “
Implications of Biochemical, Cytokinetic, Pharmacologic, and Toxicologic Relationships in the Design of Optimal Therapeutic Schedules
,”
Cancer Chemother. Rep.
,
54
(6), pp.
431
450
.
16.
Walker
,
M. C.
,
Parris
,
C. N.
, and
Masters
,
J. R.
,
1987
, “
Differential Sensitivities of Human Testicular and Bladder Tumor Cell Lines to Chemotherapeutic Drugs
,”
J. Natl. Cancer Inst.
,
79
(2), pp.
213
216
.
17.
Doroshaw
,
J.
,
1996
, “
Anthracyclines and Anthracenediones
,”
Cancer Chemotherapy and Biotherapy
,
2nd ed.
, B. Chabner and D. Longo, eds.,
Lippincott-Raven
,
Philadelphia
, pp.
409
434
.
18.
Winchester
,
J. F.
,
Rahman
,
A.
,
Tilstone
,
W. J.
,
Kessler
,
A.
,
Mortensen
,
L.
,
Schreiner
,
G. E.
,
and Schein
,
P. S.
,
1979
, “
Sorbent Removal of Adriamycin In Vitro and In Vivo
,”
Cancer Treat Rep.
,
63
(11-12), pp.
1787
1793
.
19.
Sunil
,
B.
,
Sutanjay
,
S.
, and
Manjula
,
B.
,
2007
, “
Ion Exchange Resins in Drug Delivery
,”
Ion Exchange and Solvent Extraction
,
CRC Press
, Boca Raton, FL, pp.
103
150
.
20.
Lewis
,
A. L.
,
2009
, “
DC Bead: A Major Development in the Toolbox for the Interventional Oncologist
,”
Expert Rev. Med. Devices
,
6
(4), pp.
389
400
.10.1586/erd.09.20
21.
Ku, Y., Fukumoto, T., Iwasaki, T., Tominaga, M., Samizo, M., Nishida, T., Kuroda, Y., Hirota, S., Sako, M., and Obara, H.,
1995
, “
Clinical Pilot Study on High-Dose Intraarterial Chemotherapy With Direct Hemoperfusion Under Hepatic Venous Isolation in Patients With Advanced Hepatocellular Carcinoma
,”
Surgery
,
117
(5), pp.
510
519
.10.1016/S0039-6060(05)80250-8
22.
Pingpank
,
J. F.
,
Libutti
,
S. K.
,
Chang
,
R.
,
Wood
,
B. J.
,
Neeman
,
Z.
,
Kam
,
A. W.
,
Figg
,
W. D.
,
Zhai
,
S.
,
Beresneva
,
T.
,
Seidel
,
G. D.
,
and Alexander
,
H. R.
,
2005
, “
Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies
,”
J. Clin. Oncol.
,
23
(15), pp.
3465
3474
.10.1200/JCO.2005.00.927
23.
Dougherty
,
T. B.
,
Mikolajek
,
J. A.
, and
Curley
,
S. A.
,
1997
, “
Safe Anesthetic Management of Patients Undergoing a Novel Method of Treating Human Hepatocellular Cancer
,”
J. Clin. Anesth.
,
9
(3), pp.
220
227
.10.1016/S0952-8180(97)00031-7
24.
Satyapal
,
K. S.
,
Rambiritch
,
V.
, and
Pillai
,
G.
,
1995
, “
Morphometric Analysis of the Renal Veins
,”
Anat. Rec.
,
241
(2), pp.
268
272
.10.1002/ar.1092410213
25.
Siewiorek
,
G. M.
,
Wholey
,
M. H.
, and
Finol
,
E. A.
,
2007
, “
In Vitro Performance Assessment of Distal Protection Devices for Carotid Artery Stenting: Effect of Physiological Anatomy on Vascular Resistance
,”
J. Endovasc. Ther.
,
14
(5), pp.
712
724
.10.1583/1545-1550(2007)14[712:IVPAOD]2.0.CO;2
26.
Weaver
,
M. E.
,
Pantely
,
G. A.
,
Bristow
,
J. D.
, and
Ladley
,
H. D.
,
1986
, “
A Quantitative Study of the Anatomy and Distribution of Coronary Arteries in Swine in Comparison With Other Animals and Man
,”
Cardiovasc. Res.
,
20
(12), pp.
907
917
.10.1093/cvr/20.12.907
27.
Varga-Szemes
,
A.
,
Kiss
,
P.
,
Brott
,
B. C.
,
Wang
,
D.
,
Simor
,
T.
, and
Elgavish
,
G. A.
,
2012
, “
Embozene Microspheres Induced Nonreperfused Myocardial Infarction in an Experimental Swine Model
,”
Catheterization Cardiovasc. Interv.
,
81
(4), pp. 689–697.10.1002/ccd.24418
28.
August
,
D. A.
,
Verma
,
N.
,
Andrews
,
J. C.
,
Vaerten
,
M. A.
, and
Brenner
,
D. E.
,
1994
, “
Hepatic Artery Infusion of Doxorubicin With Hepatic Venous Drug Extraction
,”
J. Surg. Res.
,
56
(6), pp.
611
619
.10.1006/jsre.1994.1097
29.
Chassany
,
O.
,
Urien
,
S.
,
Claudepierre
,
P.
,
Bastian
,
G.
, and
Tillement
,
J. P.
,
1996
, “
Comparative Serum Protein Binding of Anthracycline Derivatives
,”
Cancer Chemother. Pharmacol.
,
38
(6), pp.
571
573
.10.1007/s002800050529
30.
Ramanathan-Girish
,
S.
, and
Boroujerdi
,
M.
,
2001
, “
Contradistinction Between Doxorubicin and Epirubicin: In-Vitro Interaction With Blood Components
,”
J. Pharm. Pharmacol.
,
53
(6), pp.
815
821
.10.1211/0022357011776162
31.
Lai
,
C. L.
,
Wu
,
P. C.
,
Chan
,
G. C.
,
Lok
,
A. S.
, and
Lin
,
H. J.
,
1988
, “
Doxorubicin Versus no Antitumor Therapy in Inoperable Hepatocellular Carcinoma. A Prospective Randomized Trial
,”
Cancer
,
62
(3), pp.
479
483
.10.1002/1097-0142(19880801)62:33.0.CO;2-L
32.
Simonetti
,
R. G.
,
Liberati
,
A.
,
Angiolini
,
C.
, and
Pagliaro
,
L.
,
1997
, “
Treatment of Hepatocellular Carcinoma: A Systematic Review of Randomized Controlled Trials
,”
Ann. Oncol.
,
8
(2), pp.
117
136
.10.1023/A:1008285123736
33.
Bowles
,
E. J.
,
Wellman
,
R.
,
Feigelson
,
H. S.
,
Onitilo
,
A. A.
,
Freedman
,
A. N.
,
Delate
,
T.
,
Allen
,
L. A.
,
Nekhlyudov
,
L.
,
Goddard
,
K. A.
,
Davis
,
R. L.
,
Habel
,
L. A.
,
Yood
,
M. U.
,
McCarty
,
C.
,
Magid
,
D. J.
,
Wagner
,
E. H.
, and the Pharmacovigilance Study Team,
2012
, “
Risk of Heart Failure in Breast Cancer Patients After Anthracycline and Trastuzumab Treatment: A Retrospective Cohort Study
,”
J. Natl. Cancer Inst.
,
104
(17), pp.
1293
1305
.10.1093/jnci/djs317
34.
Hooning
,
M. J.
,
Botma
,
A.
,
Aleman
,
B. M.
,
Baaijens
,
M. H.
,
Bartelink
,
H.
,
Klijn
,
J. G.
,
Taylor
,
C. W.
,
and van Leeuwen
,
F. E.
,
2007
, “
Long-Term Risk of Cardiovascular Disease in 10-Year Survivors of Breast Cancer
,”
J. Natl. Cancer Inst.
,
99
(5), pp.
365
375
.10.1093/jnci/djk064
35.
Patnaik
,
J. L.
,
Byers
,
T.
,
DiGuiseppi
,
C.
,
Dabelea
,
D.
, and
Denberg
,
T. D.
,
2011
, “
Cardiovascular Disease Competes With Breast Cancer as the Leading Cause of Death for Older Females Diagnosed With Breast Cancer: A Retrospective Cohort Study
,”
Breast Cancer Res.
,
13
(3), p.
R64
.10.1186/bcr2901
36.
Travis
,
L. B.
,
Rabkin
,
C. S.
,
Brown
,
L. M.
,
Allan
,
J. M.
,
Alter
,
B. P.
,
Ambrosone
,
C. B.
,
Begg
,
C. B.
,
Caporaso
,
N.
,
Chanock
,
S.
,
DeMichele
,
A.
,
Figg
,
W. D.
,
Gospodarowicz
,
M. K.
,
Hall
,
E. J.
,
Hisada
,
M.
,
Inskip
,
P.
,
Kleinerman
,
R.
,
Little
,
J. B.
,
Malkin
,
D.
,
Ng
,
A. K.
,
Offit
,
K.
,
Pui
,
C. H.
,
Robison
,
L. L.
,
Rothman
,
N.
,
Shields
,
P. G.
,
Strong
,
L.
,
Taniguchi
,
T.
,
Tucker
,
M. A.
,
and Greene
,
M. H.
,
2006
, “
Cancer Survivorship—Genetic Susceptibility and Second Primary Cancers: Research Strategies and Recommendations
,”
J. Natl. Cancer Inst.
,
98
(1), pp.
15
25
.10.1093/jnci/djj001
37.
Yeh, E. T H., Tong, A. T., Lenihan, D. J., Yusuf, S. W., Swafford, J., Champion, C., Durand, J.-B., Gibbs, H., Zafarmand, A. A., and Ewer, M. S.,
2004
, “
Cardiovascular Complications of Cancer Therapy: Diagnosis, Pathogenesis, and Management
,”
Circulation
,
109
(25),
3122
3131
.10.1161/01.CIR.0000133187.74800.B9
38.
Schmitz
,
N.
,
Kloess
,
M.
,
Reiser
,
M.
,
Berdel
,
W. E.
,
Metzner
,
B.
,
Dorken
,
B.
,
Kneba
,
M.
,
Trumper
,
L.
,
Loeffler
,
M.
,
2006
, “
Four Versus Six Courses of a Dose-Escalated Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) Regimen Plus Etoposide (MegaCHOEP) and Autologous Stem Cell Transplantation: Early Dose Intensity is Crucial in Treating Younger Patients With Poor Prognosis Aggressive Lymphoma
,”
Cancer
,
106
(1), pp.
136
145
.10.1002/cncr.21588
39.
Brenner
,
H.
,
2002
, “
Long-Term Survival Rates of Cancer Patients Achieved by the End of the 20th Century: A Period Analysis
,”
Lancet
,
360
(9340), pp.
1131
1135
.10.1016/S0140-6736(02)11199-8
40.
Du
,
X. L.
,
Fox
,
E. E.
, and
Lai
,
D.
,
2008
, “
Competing Causes of Death for Women With Breast Cancer and Change Over Time From 1975 to 2003
,”
Am. J. Clin. Oncol.
,
31
(2), pp.
105
116
.10.1097/COC.0b013e318142c865
You do not currently have access to this content.