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Title: Rheumatoid Arthritis Biologic Enbrel (Etanercept) Has Potential for Treating Ovarian Cancer: Presented at EORTC-NCI-AACR

"Rheumatoid Arthritis Biologic Enbrel (Etanercept) Has Potential for Treating Ovarian Cancer: Presented at EORTC-NCI-AACR"

By Paula Moyer Special to DG News FRANKFURT, GERMANY -- November 26, 2002 -- The immunomodulator etanercept (Enbrel) may be able to treat ovarian cancer. Dr. Srinivasan Madhusudan, a medical oncologist at Churchill Hospital in Oxford, England, presented the findings here November 25 at the 14th joint meeting of the European Organisation for the Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (EORTC-NCI-AARC): Symposium on Molecular Targets and Cancer Therapeutics. "This is the first tumour necrosis factor inhibitor to be used in the treatment of ovarian cancer," he said. "Our study confirmed preclinical data that showed etanercept's potential for this type of tumour." Etanercept, which is approved for the treatment of rheumatoid arthritis, is an inhibitor of tumour necrosis factor-alpha (TNF-alpha), which plays a role in the pathogenesis of ovarian cancer, said Dr. Madhusudan. In a phase II trial involving 17 patients, they documented the effects of a 25 mg dose of etanercept given subcutaneously on a twice-weekly schedule. All patients received a minimum of three months of treatment up to a maximum of one year. The investigative team evaluated the patients' responses at three monthly intervals. The patients were a median of 54 years old, with a range of 34 to 75 years. Among these patients, 15 had optimal surgery, and two had suboptimal surgery. Among these patients, 13 had a serious subtype of tumour, one had clear cell subtype, two had endometrioid subtype, and one had mixed tumour subtypes. All of the patients had undergone previous chemotherapy consisting of carboplatin with or without paclitaxel (Taxol); of these, 12 were platinum-sensitive and five were platinum-resistant. Among these patients, 11 had undergone a second line of chemotherapy and seven had received a third line. Eleven patients had completed three months or more of etanercept treatment. The surrogate end points that Dr. Madhusudan and colleagues used to evaluate the drug's biological effect included selectin, TNF-alpha, TNF-R1, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-3 (MMP-3), which were measured in the plasma of 13 patients. The investigators also performed a whole blood cytokine release inhibition assay to assess interleukin-6 (IL-6) and MCP-1 levels. The time points at which they made their assessments were pretreatment, 24 hours, seven days, and 28 days, and then every four weeks thereafter. The investigators observed no significant toxicity, Dr. Madhusudan said. Two patients achieved stabilisation of disease for 6.3 and 10 months respectively, along with improvements in quality of life, such as reductions in fatigue, nausea, and alopecia. Median overall survival was 9.6 months. Significant reductions in IL-6 levels were observed in nine of the 13 patients for whom these data were available at the 24-hour point. Among eight of these patients, six patients maintained the reduction at 12 weeks. MCP-1 levels declined in eight of the 12 patients for whom these data were available on day 1. In six of these, levels were inhibited by 50 percent 12 weeks later. None of the other surrogate markers changed significantly with treatment, Dr. Madhusudan said. As a result of these findings, he and colleagues are treating a new cohort of patients with a three-times weekly regimen consisting of 25 mg of etanercept.

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