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PI-88. Heparanase inhibitor, Antiangiogenic agent, Oncolytic.

By Edwina N. Scott and Anne L. Thomas

Abstract

This paper was published as Drugs of the Future, 2008, 33 (1), 21. It is available from http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1165464&p_IsPs=N. Doi: 10.1358/dof.2008.033.01.1165464Metadata only entryPI-88 (phosphomannopentaose sulfate) is a mixture of sulfated oligosaccharides prepared by hydrolysis of the extracellular phosphomannan produced from the yeast Pichia holstii. It is the only heparanase inhibitor to date that has undergone clinical trials, both as a single agent and in combination with chemotherapy. The development of PI-88 has been especially exciting as it shows the most promise in two fields of oncology, melanoma and hepatocellular carcinoma, where treatment options are very limited indeed. It has been granted orphan drug status for the treatment of advanced melanoma and as adjuvant treatment following hepatocellular carcinoma resection. Toxicities seen to date include injection-site discomfort, thrombocytopenia, which may be immune-related, and thrombosis. PI-88 on the whole is well tolerated. Different schedules of s.c. PI-88 are currently under investigation, with good patient compliance as the drug is selfadministered at home. PI-88 has also been investigated in patients with non-small cell lung cancer (NSCLC), prostate cancer and multiple myeloma. Analogues of PI-88 are being developed which may confer improved efficacy and pharmacokinetic profiles compared to the parent drug

Publisher: Prous Science
Year: 2008
DOI identifier: 10.1358/dof.2008.033.01.1165464
OAI identifier: oai:lra.le.ac.uk:2381/8521
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