Treatment with the novel anti-angiogenic agent PI-88 is associated with immune-mediated thrombocytopenia.
| Autor: | Rosenthal MA; Department of Medical Oncology and Clinical Hematology, Royal Melbourne Hospital, Parkville, Victoria, Australia. mark.rosenthal@mh.org.au, Rischin D, McArthur G, Ribbons K, Chong B, Fareed J, Toner G, Green MD, Basser RL |
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| Jazyk: | angličtina |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2002 May; Vol. 13 (5), pp. 770-6. |
| DOI: | 10.1093/annonc/mdf117 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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