Source: DGNews  |  Posted 6 years ago

By Maggie Schwarz

PHILADELPHIA, PA -- November 22, 2005 -- A phase 2 study is evaluating the efficacy and toxicity associated with the use of sorafenib plus gemcitabine in patients with recurrent epithelial ovarian cancer.

In a presentation here on November 16[^]th[], Amit Oza, MD, Associate Professor of Medicine, Princess Margaret Hospital, University of Toronto, Toronto, Canada, discussed the study.

Sorafenib (BAY 43-9006) is a novel multi-targeted tyrosine kinase inhibitor that targets the RAF/MEK/ERK signaling pathway, vascular endothelial growth factor (VEGF) receptor, platelet derived growth factor receptor, and flt-3.

Phase 1 studies previously demonstrated the safety and tolerability of sorafenib in combination with gemcitabine, with preliminary activity seen in recurrent ovarian cancer.

VEGF is over-expressed in human ovarian tumours and is associated wit poor prognosis and development of ascites, Dr. Oza said. Gemcitabine is known to have single-agent activity in recurrent ovarian cancer. Therefore, sorafenib and gemcitabine are thought to make a rational therapeutic strategy for combination in recurrent ovarian cancer.

The ongoing phase 2, two-stage clinical trial is assessing the activity of sorafenib 400 mg BID administered continuously in combination with gemcitabine 1000 mg/m[^]2[] weekly.

Cycle 1 consists of gemcitabine administration for 7 weeks followed by a 1-week break, then weekly administration for the first 3 weeks of each subsequent 4-week cycle.

Twenty-five patients have been enrolled to date; 21 are evaluable for toxicity having received 42 cycles of treatment, and nine are evaluable for response.

Of patients evaluable for objective response, one patient has had a confirmed partial response and eight have had disease stabilization. These nine patients received a median of five cycles of treatment (range, one to 10 cycles).

Five patients are not evaluable for objective response; two patients had symptomatic disease progression in cycle 1, two patients withdrew consent in cycle 1 and one patient had a grade 3 bowel obstruction in cycle 1.

Grade 3 toxicities that have been seen in more than two patients to date are lymphopenia (n = 6), thrombocytopenia (n = 5), hand-foot syndrome (n = 3), pain (n = 3) and hypokalemia (n = 3).

Dr. Oza presented the study at the International Conference on Molecular Targets and Cancer Therapeutics, organized jointly by the American Association for Cancer Research, the National Cancer Institute, and the European Organisation for Research and Treatment of Cancer (AACR-NCI-EORTC).

[Presentation title: Phase II Study of Sorafenib (Bay 43-9006) in Combination with Gemcitabine in Recurrent Epithelial Ovarian Cancer: a Study of The PMH Phase II Consortium. Abstract A110]