PI-88: A novel inhibitor of angiogenesis

Expert Opinion on Investigational Drugs

Volumn 17, Issue 11, 2008, Pages 1769-1776

  Kudchadkar, Ragini ^a   Gonzalez, Rene ^a   Lewis, Karl D ^a  

^a UNIVERSITY OF COLORADO CANCER CENTER   (United States)

Author keywords

Angiogenesis; Heparan sulfate; Heparanase; Hepatocellular carcinoma; Lung cancer; Melanoma; PI 88; Prostate cancer; Vascular endothelial growth factors

Indexed keywords

ANGIOGENESIS INHIBITOR; BEVACIZUMAB; CORTICOSTEROID; DACARBAZINE; DOCETAXEL; FIBROBLAST GROWTH FACTOR; HEPARANASE; HEPARIN; MONOCLONAL ANTIBODY; PI 88; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PLATINUM COMPLEX; PROTEOHEPARAN SULFATE; SORAFENIB; SUNITINIB; TYROSINE KINASE RECEPTOR; VASCULOTROPIN; VASCULOTROPIN RECEPTOR;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTERY THROMBOSIS; ARTICLE; BRAIN HEMORRHAGE; CANCER INHIBITION; CLINICAL TRIAL; CONTINUOUS INFUSION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG ELIMINATION; DRUG EXCRETION; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG WITHDRAWAL; ENZYME INHIBITION; FEBRILE NEUTROPENIA; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; INJECTION SITE REACTION; LIVER CELL CARCINOMA; LUNG CANCER; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; MONOTHERAPY; PROSTATE CANCER; SIGNAL TRANSDUCTION; SOLID TUMOR; STRUCTURE ANALYSIS; THROMBOCYTOPENIA;

ANGIOGENESIS INHIBITORS; ANIMALS; CLINICAL TRIALS AS TOPIC; HUMANS; NEOPLASMS; OLIGOSACCHARIDES; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 54949134525     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.17.11.1769     Document Type: Article

References (25)

1. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182-6
2. Shahi P, Pindeda I. Tumoral Angiogenesis: Review of the literature. Cancer Invest 2008;26:104-8
3. Kerbel R. Tumor Angiogenesis. N Engl J Med 2008;358:2039-49
4. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005;23:1011-27
5. Joyce J, Freeman C, Meyer-Morse N, et al. A functional heparan sulfate mimetic implicates both heparanase and heparan sulfate in tumor angiogenesis and invasion in a mouse model of multistage care. Oncogene 2005;24:4037-51
6. Parish C, Freeman C, Hulett M. Heparanase: a key enzyme involved in cell invasion. Biochim Biophys Acta 2001;1471:99-108
7. Rapraeger A. The coordinated regulation of heparin sulfate, syndecans and cell behavior. Curr Opin Cell Biol 1993;5:844-53
8. Vlodavsky I, Miao H, Medalion B, et al. Involvement of heparan sulfate and related molecules in sequestration and growth promoting activity of fibroblast growth factor. Cancer Metastasis Rev 1996;15:177-86
9. Yayon A, Klagsbrun M, Esko JD, et al. Cell surface, heparin-like molecules are required for the binding of basic fibroblast growth factor to its high affinity receptor. Cell 1991;64:841-8
10. Turnbull J, Powell A, Guinmond S. Heparan sulfate: decoding a dynamic multifunctional cell regulator. Trends Cell Biol 2001;11:75-82
11. Bar-Ner M, Mayer M, Schirrmacher V, et al. Involvement of both heparanase and plasminogen activator in lymphoma cell-medicated degradation of heparan sulfate in the subendothelial extracellular matrix. J Cell Biol 1986;128:299-306
12. Francis D, Parish C, McGarry M, et al. Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88. Circ Res 2003;92:70-7
13. Risau W. Mechanism of angiogenesis. Nature 1997;386:671-4
14. Ferro V, Fewings K, Palermo M, et al. Large-scale preparation of the oligosaccharide phosphate fraction of Pichia holstii NRRL Y-2448 phosphomannan for use to manufacture of PI-88. Carbohydr Res 2001;332:183-9
15. Parish C, Freeman C, Brown K, et al. Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity. Cancer Res 1999;59:3433-41
16. King A, Dickenson RG. Disposition of 35S-PI-88 following intravenous, oral and subcutaneous administration to mate rats. Centre Stud Drug Dispos, May 2002
17. Marriott L. The disposition of total radioactivity in the cynomolgus monkey following single oral, single subcutaneous and single intravenous administration of [35S]PI-88. Quintiles Preclinical Services report no. DESW1001, 12 March 2002
18. Basche M, Gustafon D, Holden S, et al. A Phase I pharmacological and biological study of heparanase inhibitor PI-88 in patients with advanced solid tumors. Clin Cancer Res 2006;12:5471-80
19. PI-88 Investigators Brochure, edition 10, Progen Pharmaceuticals Ltd., Brisbane; May 30,2008
20. Rosenthal MA, Rischin D, McArthur G, et al. Treatment with the novel anti-angiogenic agent PI-88 is associated with immune mediated thrombocytopenia. Ann Oncol 2002;13:770-6
21. Chow L, Gustafon D, O'Bryant C, et al. A Phase I pharmacological and biological study of PI-88 and docetaxel in patients with advanced malignancies. Cancer Chemother Pharmacol 2008;[Epub]
22. Lewis KD, Robinson WA, Millward MJ, et al. A Phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma. Invest New Drugs 2008;26:89-94
23. Millward M, Hamilton A, Thomson D, et al. Final results of a Phase I study of daily PI-88 as a single agent and in combination with dacarbazine (D) in patients with metastatic melanoma [abstract 8532]. J Clin Oncol 2007;25(18S):
24. Marx GM, Pavlakis N, McCowatt S, et al. Phase I/II study of PI-88, a novel heparanase inhibitor, in combination with docetaxel (D) in patients with hormone refractory prostate cancer (HRPC) [abstract 182]. Am Soc Clin Oncol 2008;Genitourinary Cancers Symposium
25. Chen PJ, Lee PH, Lin DY, et al. PI-88, a Novel Heparanase Inhibitor, as adjuvant therapy for Hepatocellular Carcinoma: A Large randomised Phase II Clinical Trial. EASL Annual Meeting; Barcelona Spain, April 11-15 2007