By Michael Casasnovas
TAMPA, Fla -- March 14, 2008 -- Women with ovarian cancer that is resistant to platinum-based chemotherapy appear to respond to treatment with the novel agent SNS-595, researchers said here at the Society of Gynecologic Oncologists (SGO) 2008 Annual Meeting on Women's Cancer.
"SNS-595 has demonstrated clinical activity in patients with platinum-resistant ovarian cancer, several of whom have failed prior therapy with pegylated liposomal doxorubicin as well," said William McGuire, MD, Clinical Professor of Medicine, University of Maryland School of Medicine, and Director, Harriett and Jeanette Weinberg Cancer Institute, Franklin Square Hospital Center, Baltimore, Maryland.
SNS-595, which being developed by Sunesis Pharmaceuticals, South San Francisco, California, is delivered intravenously and has shown activity in several cancers, including acute leukaemia, ovarian cancer, non-small-cell lung cancer, and small-cell lung cancer. SNS-595 is a DNA-damaging agent that causes irreversible growth arrest and promotes apoptosis of cancer cells.
Dr. McGuire and colleagues treated 65 women with advanced platinum-resistant epithelial ovarian cancer with progressive disease. In a poster presentation on March 11, he reported on outcomes in 35 of the women for whom evaluation was possible. The women were about 57 years of age and most were white. The patients had previously progressed on a median of two platinum-based therapies. Nineteen of the women progressed despite previous treatment with pegylated liposomal doxorubicin in addition to platinum therapy.
Patients were eligible for enrolment in the study if they had a good performance status and adequate haematological, hepatic, and renal status. Doctors administered SNS-595 over 10 minutes on day 1 of a 21-day cycle at doses of 48 mg/m2 for 6 cycles with a possibility of extending the cycles further. The most common adverse events consisted of nausea, fatigue, and alopecia.
Dr. McGuire said that 1 of the 35 evaluable patients achieved a complete response, 4 patients achieved partial responses, and 26 patients were able to stabilise their disease. The other 4 patients experienced disease progression.
Incidence of treatment-related adverse events was low, Dr. McGuire said. "The rate of febrile neutropenia in this study is low (9%), indicating that SNS-595 is a generally well-tolerated drug in this population," he said.
In preclinical studies, SNS-595 appeared to be a potent inhibitor of proliferation of tumour cells derived from ovarian biopsies, according to Dr. McGuire and colleagues.
Given the safety profile observed to date, as well as encouraging indications of activity, the dose of SNS-595 has been increased to 60 mg/m2 and cycling has been extended to 28 days. The study continues to enrol patients.
Funding for this study was provided by Sunesis Pharmaceuticals
[Presentation title: A Phase 2 Trial of SNS-595 in Women With Platinum Resistant Epithelial Ovarian Cancer. Abstract 290]
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