Cancer Research SABCS Protein Translation and Cancer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kisker, O.
Right arrow Articles by Folkman, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kisker, O.
Right arrow Articles by Folkman, J.
[Cancer Research 61, 7669-7674, October 15, 2001]
© 2001 American Association for Cancer Research

Tumor Biology

Continuous Administration of Endostatin by Intraperitoneally Implanted Osmotic Pump Improves the Efficacy and Potency of Therapy in a Mouse Xenograft Tumor Model1

Oliver Kisker, Christian M. Becker, Daniela Prox, Michael Fannon, Robert D’Amato, Evelyn Flynn, William E. Fogler, B. Kim Lee Sim, Elizabeth N. Allred, Steven R. Pirie-Shepherd2 and Judah Folkman3

Division of Surgical Research [O. K., C. M. B., D. P., M. F., R. D., E. F., S. R. P-S., J. F.] and Department of Neurology [E. N. A.], Children’s Hospital, Boston, Massachusetts 02115; University Hospital Marburg, Department of General Surgery, Philipps University, Marburg, Germany [O. K.]; University Hospital Benjamin Franklin, Department of Gynecology and Obstetrics, Free University Berlin, Berlin, Germany [C. M. B.]; Departments of Ophthalmology [R. D.] and Surgery and Cell Biology [J. F.], Harvard Medical School Boston, Massachusetts 02115; and EntreMed, Inc., Rockville, Maryland 20850 [W. E. F., B. K. L. S.]

In the first Phase I clinical trials of endostatin as an antiangiogenic therapy for cancer, the protein was administered as an i.v. bolus for ~20–30 min each day. This protocol was based on experimental studies in which animals were treated by s.c. bolus once a day. However, it was not clear in the previous studies whether this schedule could be maximized further. Therefore, we developed experimental models involving continuous administration of endostatin to determine the potency and efficacy of this approach. Endostatin was administered to tumor-bearing mice either s.c. or i.p. in single bolus doses. The efficacy of these regimens was compared with endostatin administered continuously via an i.p. implanted mini-osmotic pump. Our results show that endostatin remains stable and active in mini-osmotic pumps for at least 7 days. We show that endostatin injected i.p. is rapidly cleared within 2 h, whereas endostatin administered continuously via mini-osmotic pump maintains systemic concentrations of 200–300 ng/ml for the duration of administration. Furthermore, continuous i.p. administration of endostatin results in more effective tumor suppression at significantly reduced doses (5-fold), compared with bolus administration. Additional experiments using a human pancreatic cancer model in severe combined immunodeficient mice showed that there was a significant decrease in the microvessel density between the treatment groups and the control group. These data show that continuous administration of human endostatin results in sustained systemic concentrations of the protein leading to: (a) increased efficacy manifested as increased tumor regression; and (b) an 8–10-fold decrease in the dose required to achieve the same antitumor effect as the single daily bolus administration of endostatin. On the basis of this approach, an additional clinical trial has been designed and initiated and is under way in two countries.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
E. Briasoulis, P. Pappas, C. Puozzo, C. Tolis, G. Fountzilas, U. Dafni, M. Marselos, and N. Pavlidis
Dose-Ranging Study of Metronomic Oral Vinorelbine in Patients with Advanced Refractory Cancer
Clin. Cancer Res., October 15, 2009; 15(20): 6454 - 6461.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. Lu, K. Zhang, S. Chen, and W. Wen
Grape seed extract inhibits VEGF expression via reducing HIF-1{alpha} protein expression
Carcinogenesis, April 1, 2009; 30(4): 636 - 644.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Prevention ResearchHome page
W. Wen, J. Lu, K. Zhang, and S. Chen
Grape Seed Extract Inhibits Angiogenesis via Suppression of the Vascular Endothelial Growth Factor Receptor Signaling Pathway
Cancer Prevention Research, December 1, 2008; 1(7): 554 - 561.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. G. Marneros, H. She, H. Zambarakji, H. Hashizume, E. J. Connolly, I. Kim, E. S. Gragoudas, J. W. Miller, and B. R. Olsen
Endogenous endostatin inhibits choroidal neovascularization
FASEB J, December 1, 2007; 21(14): 3809 - 3818.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
Y. Fu, M. L. Ponce, M. Thill, P. Yuan, N. S. Wang, and K. G. Csaky
Angiogenesis Inhibition and Choroidal Neovascularization Suppression by Sustained Delivery of an Integrin Antagonist, EMD478761
Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5184 - 5190.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
X. Zhang, J. Xu, J. Lawler, E. Terwilliger, and S. Parangi
Adeno-Associated Virus-Mediated Antiangiogenic Gene Therapy with Thrombospondin-1 Type 1 Repeats and Endostatin
Clin. Cancer Res., July 1, 2007; 13(13): 3968 - 3976.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. C.M. Martinico, S. Jezzard, N. J. H. Sturt, G. Michils, S. Tejpar, R. K. Phillips, and G. Vassaux
Assessment of Endostatin Gene Therapy for Familial Adenomatous Polyposis-Related Desmoid Tumors
Cancer Res., August 15, 2006; 66(16): 8233 - 8240.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. H. Kulke, E. K. Bergsland, D. P. Ryan, P. C. Enzinger, T. J. Lynch, A. X. Zhu, J. A. Meyerhardt, J. V. Heymach, W. E. Fogler, C. Sidor, et al.
Phase II Study of Recombinant Human Endostatin in Patients With Advanced Neuroendocrine Tumors
J. Clin. Oncol., August 1, 2006; 24(22): 3555 - 3561.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
X.-P. Li, C. Y.S. Li, X. Li, Y. Ding, L. L.Y. Chan, P.-H. Yang, G. Li, X. Liu, J. S. Lin, J. Wang, et al.
Inhibition of human nasopharyngeal carcinoma growth and metastasis in mice by adenovirus-associated virus-mediated expression of human endostatin
Mol. Cancer Ther., May 1, 2006; 5(5): 1290 - 1298.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. E. M. Dirkx, M. G. A. oude Egbrink, K. Castermans, D. W. J. van der Schaft, V. L. J. L. Thijssen, R. P. M. Dings, L. Kwee, K. H. Mayo, J. Wagstaff, J. C. A. B. ter Steege, et al.
Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors
FASEB J, April 1, 2006; 20(6): 621 - 630.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I. Celik, O. Surucu, C. Dietz, J. V. Heymach, J. Force, I. Hoschele, C. M. Becker, J. Folkman, and O. Kisker
Therapeutic Efficacy of Endostatin Exhibits a Biphasic Dose-Response Curve
Cancer Res., December 1, 2005; 65(23): 11044 - 11050.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
A. H. G. Hansma, H. J. Broxterman, I. van der Horst, Y. Yuana, E. Boven, G. Giaccone, H. M. Pinedo, and K. Hoekman
Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer
Ann. Onc., October 1, 2005; 16(10): 1695 - 1701.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
H.-M. Cho, J. D. Rosenblatt, Y.-S. Kang, M. L. Iruela-Arispe, S. L. Morrison, M. L. Penichet, Y.-G. Kwon, T.-W. Kim, K. A. Webster, H. Nechustan, et al.
Enhanced inhibition of murine tumor and human breast tumor xenografts using targeted delivery of an antibody-endostatin fusion protein
Mol. Cancer Ther., June 1, 2005; 4(6): 956 - 967.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. M. Tjin Tham Sjin, R. Satchi-Fainaro, A. E. Birsner, V.M. S. Ramanujam, J. Folkman, and K. Javaherian
A 27-Amino-Acid Synthetic Peptide Corresponding to the NH2-Terminal Zinc-Binding Domain of Endostatin Is Responsible for Its Antitumor Activity
Cancer Res., May 1, 2005; 65(9): 3656 - 3663.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
X. Zhang, E. Galardi, M. Duquette, M. Delic, J. Lawler, and S. Parangi
Antiangiogenic Treatment with the Three Thrombospondin-1 Type 1 Repeats Recombinant Protein in an Orthotopic Human Pancreatic Cancer Model
Clin. Cancer Res., March 15, 2005; 11(6): 2337 - 2344.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. K. Skovseth, M. J. T. Veuger, D. R. Sorensen, P. M. De Angelis, and G. Haraldsen
Endostatin dramatically inhibits endothelial cell migration, vascular morphogenesis, and perivascular cell recruitment in vivo
Blood, February 1, 2005; 105(3): 1044 - 1051.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
O. Benny, M. Duvshani-Eshet, T. Cargioli, L. Bello, A. Bikfalvi, R. S. Carroll, and M. Machluf
Continuous Delivery of Endogenous Inhibitors from Poly(Lactic-Co-Glycolic Acid) Polymeric Microspheres Inhibits Glioma Tumor Growth
Clin. Cancer Res., January 15, 2005; 11(2): 768 - 776.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A.-K. Olsson, I. Johansson, H. Akerud, B. Einarsson, R. Christofferson, T. Sasaki, R. Timpl, and L. Claesson-Welsh
The Minimal Active Domain of Endostatin Is a Heparin-Binding Motif that Mediates Inhibition of Tumor Vascularization
Cancer Res., December 15, 2004; 64(24): 9012 - 9017.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
K. S. Moulton, B. R. Olsen, S. Sonn, N. Fukai, D. Zurakowski, and X. Zeng
Loss of Collagen XVIII Enhances Neovascularization and Vascular Permeability in Atherosclerosis
Circulation, September 7, 2004; 110(10): 1330 - 1336.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. K. Chang, G. Garcia-Cardena, F. Farnebo, M. Fannon, E. J. Chen, C. Butterfield, M. A. Moses, R. C. Mulligan, J. Folkman, and A. Kaipainen
Dose-dependent response of FGF-2 for lymphangiogenesis
PNAS, August 10, 2004; 101(32): 11658 - 11663.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. L. Feldman, W. G. Stetler-Stevenson, N. G. Costouros, V. Knezevic, G. Baibakov, H. R. Alexander Jr., D. Lorang, S. M. Hewitt, D.-W. Seo, M. S. Miller, et al.
Modulation of Tumor-host Interactions, Angiogenesis, and Tumor Growth by Tissue Inhibitor of Metalloproteinase 2 via a Novel Mechanism
Cancer Res., July 1, 2004; 64(13): 4481 - 4486.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Yu, K. S. Moulton, M. K. Khan, S. Vineberg, E. Boye, V. M. Davis, P. E. O'Donnell, J. Bischoff, and D. S. Milstone
E-selectin is required for the antiangiogenic activity of endostatin
PNAS, May 25, 2004; 101(21): 8005 - 8010.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. W. Nap, A. W. Griffioen, G. A. J. Dunselman, J. C. A. Bouma-Ter Steege, V. L. J. L. Thijssen, J. L. H. Evers, and P. G. Groothuis
Antiangiogenesis Therapy for Endometriosis
J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1089 - 1095.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Ponnazhagan, G. Mahendra, S. Kumar, D. R. Shaw, C. R. Stockard, W. E. Grizzle, and S. Meleth
Adeno-Associated Virus 2-Mediated Antiangiogenic Cancer Gene Therapy: Long-Term Efficacy of a Vector Encoding Angiostatin and Endostatin over Vectors Encoding a Single Factor
Cancer Res., March 1, 2004; 64(5): 1781 - 1787.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. O. Schmidt, M. Ziu, G. Carrabba, C. Giussani, L. Bello, Y. Sun, K. Schmidt, M. Albert, P. Mcl. Black, and R. S. Carroll
Antiangiogenic Therapy by Local Intracerebral Microinfusion Improves Treatment Efficiency and Survival in an Orthotopic Human Glioblastoma Model
Clin. Cancer Res., February 15, 2004; 10(4): 1255 - 1262.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. I. Kim, K. S. Kim, H. S. Kim, D. S. Kim, Y. Jang, K. H. Chung, and Y. S. Park
Inhibitory Effect of the Salmosin Gene Transferred by Cationic Liposomes on the Progression of B16BL6 Tumors
Cancer Res., October 1, 2003; 63(19): 6458 - 6462.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
D Kurosaka, K Yoshida, J Yasuda, T Yokoyama, I Kingetsu, N Yamaguchi, K Joh, M Matsushima, S Saito, and A Yamada
Inhibition of arthritis by systemic administration of endostatin in passive murine collagen induced arthritis
Ann Rheum Dis, July 1, 2003; 62(7): 677 - 679.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Giussani, G. Carrabba, M. Pluderi, V. Lucini, M. Pannacci, D. Caronzolo, F. Costa, M. Minotti, G. Tomei, R. Villani, et al.
Local Intracerebral Delivery of Endogenous Inhibitors by Osmotic Minipumps Effectively Suppresses Glioma Growth in Vivo
Cancer Res., May 15, 2003; 63(10): 2499 - 2505.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
R. Auerbach, R. Lewis, B. Shinners, L. Kubai, and N. Akhtar
Angiogenesis Assays: A Critical Overview
Clin. Chem., January 1, 2003; 49(1): 32 - 40.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Capillo, P. Mancuso, A. Gobbi, S. Monestiroli, G. Pruneri, C. Dell'Agnola, G. Martinelli, L. Shultz, and F. Bertolini
Continuous Infusion of Endostatin Inhibits Differentiation, Mobilization, and Clonogenic Potential of Endothelial Cell Progenitors
Clin. Cancer Res., January 1, 2003; 9(1): 377 - 382.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Bocci, K. C. Nicolaou, and R. S. Kerbel
Protracted Low-Dose Effects on Human Endothelial Cell Proliferation and Survival in Vitro Reveal a Selective Antiangiogenic Window for Various Chemotherapeutic Drugs
Cancer Res., December 1, 2002; 62(23): 6938 - 6943.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
N. Ortega and Z. Werb
New functional roles for non-collagenous domains of basement membrane collagens
J. Cell Sci., November 15, 2002; 115(22): 4201 - 4214.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. H. M. Schellens and M. J. Ratain
Endostatin: Are the 2 Years Up Yet?
J. Clin. Oncol., September 15, 2002; 20(18): 3758 - 3760.
[Full Text] [PDF]

Home page
 JCOHome page
J. P. Eder Jr, J. G. Supko, J. W. Clark, T. A. Puchalski, R. Garcia-Carbonero, D. P. Ryan, L. N. Shulman, J. Proper, M. Kirvan, B. Rattner, et al.
Phase I Clinical Trial of Recombinant Human Endostatin Administered as a Short Intravenous Infusion Repeated Daily
J. Clin. Oncol., September 15, 2002; 20(18): 3772 - 3784.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. S. Herbst, K. R. Hess, H. T. Tran, J. E. Tseng, N. A. Mullani, C. Charnsangavej, T. Madden, D. W. Davis, D. J. McConkey, M. S. O'Reilly, et al.
Phase I Study of Recombinant Human Endostatin in Patients With Advanced Solid Tumors
J. Clin. Oncol., September 15, 2002; 20(18): 3792 - 3803.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. A. Scappaticci
Mechanisms and Future Directions for Angiogenesis-Based Cancer Therapies
J. Clin. Oncol., September 15, 2002; 20(18): 3906 - 3927.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Ye, C. Feng, S. Wang, X. Liu, Y. Lin, and M. Li
Antiangiogenic and Antitumor Effects of Endostatin on Follicular Thyroid Carcinoma
Endocrinology, September 1, 2002; 143(9): 3522 - 3528.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
E. M. Hammond, A. J. Giaccia, T. Browder, J. Folkman, P. Hahnfeldt, J. Heymach, L. Hlatky, M. Kieran, M. S. Rogers, Robert. S. Kerbel, et al.
Antiangiogenic Therapy and p53
Science, July 26, 2002; 297(5581): 471a - 471.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.