A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma.

Abstract

Treatment options for advanced melanoma are limited. PI-88, a potent inhibitor of heparanase, demonstrates anitangiogenic properties and has shown activity against melanoma in phase I studies. This was an open-label, multicenter, phase II study of PI-88 in patients with advanced melanoma. Patients received a fixed-dose of 250 mg/day given subcutaneously for four consecutive days followed by three drug-free days per week in a 28-day cycle. A total of 44 patients were enrolled in the intent to treat population, with 59.1% having received previous therapy. The median time to progression and overall survival was 1.7 months and 9 months, respectively. Forty-one patients are included in the efficacy analysis. One (2.4%) patient achieved a partial response, six (14.6%) patients had stable disease as best response, and 30 (73.2%) had progressive disease. At the end of six cycles of treatment, three of the 41 evaluable patients had non-progressive disease. Treatment was generally well tolerated. Injection site bruising occurred in 45% of patients. Serious bleeding did occur in two patients and three patients developed a positive anti-platelet antibody test during the study. One of these four patients experienced an associated thrombosis. In patients with advanced melanoma, PI-88 demonstrates an overall survival and time to progression similar to standard chemotherapy. Although the current study did not meet the primary end-point of progression free survival of >or=20%, there is some evidence of activity and further investigation is warranted.

• Authors: Karl D Lewis, William A Robinson, Michael J Millward, Alex Powell, Timothy J Price, Damien B Thomson, Euan T Walpole, Andrew M Haydon, Brian R Creese, Kaye L Roberts, John R Zalcberg, Rene Gonzalez
• Journal: Investigational new drugs (Invest New Drugs) Vol. 26 Issue 1 Pg. 89-94 (Feb 2008) ISSN: 0167-6997 [Print] United States
• PMID: 17891338 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Oligosaccharides
• phosphomannopentaose sulfate
• Alanine Transaminase
• heparanase
• Glucuronidase

Topics

• Adult
• Aged
• Alanine Transaminase (blood)
• Contusions (etiology)
• Drug Administration Schedule
• Fatigue (chemically induced)
• Female
• Glucuronidase (antagonists & inhibitors)
• Humans
• Injections, Subcutaneous (adverse effects)
• Kaplan-Meier Estimate
• Male
• Melanoma (drug therapy, pathology)
• Middle Aged
• Nausea (chemically induced)
• Neoplasm Metastasis
• Oligosaccharides (administration & dosage, adverse effects, therapeutic use)
• Pain (etiology)
• Severity of Illness Index
• Thrombocytopenia (chemically induced)
• Treatment Outcome