TY - JOUR
T1 - A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma
AU - Lewis, Karl D.
AU - Robinson, William A.
AU - Millward, Michael J.
AU - Powell, Alex
AU - Price, Timothy J.
AU - Thomson, Damien B.
AU - Walpole, Euan T.
AU - Haydon, Andrew M.
AU - Creese, Brian R.
AU - Roberts, Kaye L.
AU - Zalcberg, John R.
AU - Gonzalez, Rene
PY - 2008/2/1
Y1 - 2008/2/1
N2 - 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.
AB - 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.
KW - Heparanase inhibitor
KW - Melanoma
KW - PI-88
UR - https://www.scopus.com/pages/publications/38149089538
U2 - 10.1007/s10637-007-9080-5
DO - 10.1007/s10637-007-9080-5
M3 - Article
C2 - 17891338
AN - SCOPUS:38149089538
SN - 0167-6997
VL - 26
SP - 89
EP - 94
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 1
ER -