Treatment with the novel anti-angiogenic agent PI-88 is associated with immune-mediated thrombocytopenia

M. A. Rosenthal, D. Rischin, G. McArthur, K. Ribbons, B. Chong, J. Fereed, G. Toner, M. D. Green, R. L. Basser

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Background: The novel molecule PI-88 is a highly sulfonated oligosaccharide which inhibits heparanase activity and competes with heparan sulfate binding of growth factors such as FGF and VEGF. Preclinical data demonstrates that PI-88 inhibits angiogenesis and has anti-metastatic effects. The aim of this phase I study was to determine the recommended dose and toxicity profile of PI-88. Patients and Methods: PI-88 was given intravenously in increasing duration of administration (0.57 mg/kg for 2 h, 0.57 mg/kg/day for 1 day, 4, 7 and 14 consecutive days) and then increasing dose for 14 consecutive days (1.14 mg/kg/day and 2.28 mg/kg/day) in patients with advanced malignancies until dose-limiting toxicity (DLT) was observed. Fourteen assessable patients with advanced malignancies received PI-88 intravenously. Results: DLT was thrombocytopenia. The thrombocytopenia appeared to be immunologically mediated with the development of anti-heparin platelet factor 4 complex antibodies. There were no other significant toxicities. At the final dose and schedule (2.28 mg/kg/day for 14 days), there was limited evidence of biological activity as measured by the surrogate marker activated partial thromboplastin time (APTT), although two patients had stabilisation of disease. Conclusions: In conclusion, PI-88 at a dose of 2.28 mg/kg/day for 14 days resulted in dose-limiting thrombocytopenia which appeared to be immune related. Limited evidence of biological activity was noted. Alternate scheduling and routes of administration are now being explored.

Original languageEnglish
Pages (from-to)770-776
Number of pages7
JournalAnnals of Oncology
Issue number5
StatePublished - 1 Jan 2002
Externally publishedYes


  • Anti-angiogenic
  • PI-88
  • Thrombocytopenia

ASJC Scopus subject areas

  • Hematology
  • Oncology


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