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| |  Incel May Reduce Disease Progression In Ovarian Cancer Patients WASHINGTON, DC -- November 18, 1999 -- Vertex Pharmaceuticals Incorporated reported interim results of a Phase II clinical trial of Incel(TM) (biricodar dicitrate), in combination with paclitaxel, for treatment of ovarian cancer refractory to chemotherapy. Study results suggest that Incel was well-tolerated and may restore tumor sensitivity to chemotherapy, as measured by a 12 percent objective tumor response rate and a greater than or equal to 50 percent reduction in CA-125 levels (a marker for ovarian cancer disease progression) in 52 percent of patients. The data were reported in a poster session at the American Association for Cancer Research-National Cancer Institute- European Organization for Research and Treatment of Cancer (AACR-NCI-EORTC) International Conference, being held this week in Washington, DC.
"In this study of ovarian cancer patients who had failed a prior course of paclitaxel, we saw evidence that Incel can restore or enhance the activity of a subsequent course of paclitaxel," said Dr. Michael Seiden, Assistant Professor of Medicine, Gillette Center for Women's Cancers at Massachusetts General Hospital, and a lead investigator on the study. "These data suggest that ovarian tumor resistance mechanisms can be partially, and in one case, completely, reversed. We are continuing the study to assess the efficacy Incel may have in a larger number of ovarian cancer patients." The Phase II clinical trial is evaluating the safety, tolerability, pharmacokinetics and efficacy of Incel administered intravenously in combination with paclitaxel to patients with ovarian cancer refractory to paclitaxel therapy. Approximately 55 patients are expected to enroll in the study. At interim analysis, there were 25 evaluable patients. Patients enrolled in the study have advanced ovarian cancer, with a diagnosis of either progressive disease after failing prior treatment with paclitaxel, or relapsing disease within four months of study entry. The treatment regimen consists of 120 mg/m2/hr of Incel, administered by intravenous infusion over a 24-hour period, and 80 mg/m2 of paclitaxel, administered intravenously over a 3-hour period. This regimen is repeated every 21 days. The interim analysis shows that treatment with Incel and paclitaxel is well-tolerated. The incidence of adverse events is similar to those associated with treatment with paclitaxel therapy alone. The interim analysis of the Phase II study demonstrates that the Incel/paclitaxel combination displays anti-tumor activity in patients with treatment-refractory advanced ovarian cancer. In this study, three out of 25 patients (12 percent) exhibited an objective tumor response, based on a significant reduction in tumor size (greater than or equal to 50 percent) after treatment with Incel and paclitaxel. One patient achieved a complete response, with no detectable tumor evident after treatment with Incel and paclitaxel. Two patients achieved a partial response, with 50 percent or more tumor regression observed after treatment with Incel and paclitaxel. Among the three patients who achieved an objective response to therapy, the duration of response ranged from 1.5 months to longer than three months. In two of the three patients with objective response to therapy, their cancer had progressed on previous treatment with paclitaxel. Twelve of 23 patients (52 percent) with an elevated CA-125 level had a 50 percent or greater reduction in CA-125 levels that was sustained for up to 24 weeks following treatment with Incel and paclitaxel. CA-125 is a blood protein marker for ovarian tumors. Reductions in CA-125 levels have been correlated with improved outcome in retrospective studies of ovarian cancer patients. "These findings are among the strongest for Incel to date, and support the strategy of overcoming or reversing cancer multidrug resistance by blocking drug pumps that may be overexpressed in tumors," said Dr. Vicki Sato, Senior Vice President of Research and Development and Chief Scientific Officer of Vertex. "Based on results to date, we believe that ovarian cancer is a promising indication in which to pursue Phase III development and product registration. Pending further results from our remaining ongoing studies, including the study in small cell lung cancer, we anticipate initiating Phase III trials with Incel." Ovarian cancer is diagnosed in about 27,000 American women annually. About 15,000 women die of the disease every year. Paclitaxel is a widely used chemotherapy agent approved for treatment of advanced ovarian cancer and breast cancer. Approximately 70 percent of advanced ovarian cancer patients receive paclitaxel therapy, and the majority of patients relapse following their initial therapy. Multidrug resistance significantly limits the efficacy of many cancer chemotherapy regimens and is a major factor in the failure of cancer chemotherapy. Clinical response to therapy is correlated to the presence of molecular "pumps" that expel chemotherapy drugs from the tumor cells, and thus prevent the cancer from being eliminated. Two drug pumps commonly found in cancer are P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP). Vertex's research suggests that Incel can enhance the accumulation of chemotherapy agents in tumor cells by blocking both P-gp and MRP, and thereby restore the sensitivity of tumor cells to treatment with chemotherapeutic agents. P-gp and MRP overexpression have been associated with ovarian cancer that is refractory to chemotherapy. BioChem Pharma Inc. (Nasdaq:BCHE; ME, TSE:BCH), Vertex's partner for the development and marketing of Incel in Canada, participated in the ovarian cancer trials. Vertex Pharmaceuticals Incorporated discovers, develops and markets small molecule drugs that address major unmet medical needs. The Company has nine drug candidates in clinical development to treat viral diseases, inflammation, cancer, autoimmune diseases and neurological disorders. Vertex has created its pipeline using a proprietary approach, information-based drug design, that integrates multiple technologies in biology, chemistry and biophysics aimed at increasing the speed and success rate of drug discovery. Vertex's first approved product is Agenerase(TM) (amprenavir), an HIV protease inhibitor, which Vertex co-promotes with Glaxo Wellcome.
Related Link: Vertex Pharmaceuticals Incorporated and BioChem Pharma Inc.
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