A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma
| Autor: | Brian R. Creese, Michael Millward, Andrew Haydon, Alex Powell, Timothy J. Price, Damien Thomson, Euan Walpole, Rene Gonzalez, Karl D. Lewis, Kaye L. Roberts, William A. Robinson, John Zalcberg |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Nausea medicine.medical_treatment Contusions Injections Subcutaneous Population Phases of clinical research Oligosaccharides Pain Kaplan-Meier Estimate Gastroenterology Severity of Illness Index Drug Administration Schedule Internal medicine medicine Humans Pharmacology (medical) Progression-free survival Neoplasm Metastasis education Melanoma Fatigue Aged Glucuronidase Pharmacology education.field_of_study Chemotherapy Intention-to-treat analysis business.industry Alanine Transaminase Middle Aged medicine.disease Thrombocytopenia Surgery Treatment Outcome Oncology Female medicine.symptom business Progressive disease |
| Zdroj: | Investigational new drugs. 26(1) |
| ISSN: | 0167-6997 |
| Popis: | 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 >/=20%, there is some evidence of activity and further investigation is warranted. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink