title: 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: Cutaneous Oncology Program, University of Colorado Health Sciences Center, PO Box 6510, Mail Stop F703, Aurora, CO 80045, USA. karl.lewis@uchsc.edu
authors: Karl D
authors: KD
authors: Lewis
authors: William A
authors: WA
authors: Robinson
authors: Michael J
authors: MJ
authors: Millward
authors: Alex
authors: A
authors: Powell
authors: Timothy J
authors: TJ
authors: Price
authors: Damien B
authors: DB
authors: Thomson
authors: Euan T
authors: ET
authors: Walpole
authors: Andrew M
authors: AM
authors: Haydon
authors: Brian R
authors: BR
authors: Creese
authors: Kaye L
authors: KL
authors: Roberts
authors: John R
authors: JR
authors: Zalcberg
authors: Rene
authors: R
authors: Gonzalez
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D003288:Contusions / Q000209:etiology; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D006801:Humans; D007279:Injections, Subcutaneous / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D009844:Oligosaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D000099175:Heparanase
chemical_list: D000410:Alanine Transaminase; D005966:Glucuronidase; D009844:Oligosaccharides; D000099175:Heparanase; C120158:phosphomannopentaose sulfate