If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  Incel Enhances Efficacy Of Chemotherapy In Prostate Cancer Patients WASHINGTON, DC -- November 18, 1999 -- Vertex Pharmaceuticals Incorporated reported results of a Phase II clinical trial of Incel(TM) (biricodar dicitrate) for treatment of advanced hormone-refractory prostate cancer. The trial results suggest that Incel has activity against cancer multidrug resistance, contributing to reduction of PSA levels in some patients who had not previously received treatment with chemotherapeutic agents. Nine of 33 patients (27 percent) on study achieved a partial response, defined as a drop in serum PSA levels of 80 percent or more, and in each patient the response was sustained for greater than 6 weeks. The data were reported 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 prostate cancer patients, we saw that Incel may enhance the activity of mitoxantrone/prednisone, which is one of a few approved treatments for this late-stage, hormone-refractory population," said Dr. Randy Rago, Assistant Professor of Medicine, Division of Medical Oncology and Hematology, Genitourinary Oncology Program, at H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida and a lead investigator on the study. "These data suggest that Incel, an inhibitor of multidrug resistance, may offer a therapeutic benefit to patients who have not previously received chemotherapeutic agents." The Phase II clinical trial evaluated the safety, tolerability, pharmacokinetics, and efficacy of Incel in combination with Novantrone(R) (mitoxantrone) and prednisone in hormone-refractory prostate cancer. Upon enrollment in the study, all 33 evaluable patients had progressive prostatecancer refractory to hormone therapy. The trial has completed enrollment with 40 patients. Patients received 120 mg/m2/hr of Incel, administered by intravenous infusion over a 72-hour period, 12 mg/m2 of mitoxantrone, administered intravenously 4 hours after the start of the Incel infusion, and 5 mg of prednisone twice a day. This regimen was repeated every 21 days. The trial measured reduction of serum prostate specific antigen (PSA), a prostate tumor marker, from baseline values upon study entry. Results of the trial showed that 13 of 33 patients (39 percent) had a 50 percent or greater reduction in serum PSA levels, and 9 of these 13 patients (27 percent of patients in the study) had an 80 percent or greater reduction in serum PSA levels. The 80 percent or greater drop in serum PSA levels qualified as a partial response in this study. In each of the nine patients (27 percent) whose PSA decline was greater than or equal to 80 percent, this decrease was sustained for greater than six weeks. In a previously published clinical trial that treated patients with mitoxantrone and hydrocortisone alone, only 7 percent of patients achieved a PSA decline greater than or equal to 80 percent lasting for more than six weeks. Both prednisone and hydrocortisone are corticosteriods used in chemotherapeutic regimens. Treatment with Incel and mitoxantrone/prednisone was well-tolerated. Adverse events observed in the study were similar to those experienced by patients treated with mitoxantrone/prednisone alone. "This data indicates that Incel may increase both the depth and duration of response to treatment with mitoxantrone and prednisone," said Dr. Vicki Sato, Senior Vice President of Research and Development and Chief Scientific Officer of Vertex. "Long-term follow-up on these patients will help determine Incel's potential clinical benefit and its potential to increase quality of Prostate cancer is the most common solid tumor cancer in the United States. The American Cancer Society estimates that there will be about 179,300 new cases of prostate cancer in the United States this year, and about 37,000 men will die of this disease. Many patients go on to develop advanced cancer that is not responsive to treatment with hormonal therapy. The study is part of a broad Phase II program evaluating Incel's potential to resensitize drug-resistant tumors to chemotherapy in a range of cancer types and therapeutic regimens, with the goal of designing Phase III clinical trials of Incel in cancer patients. Phase II studies of the activity of Incel in patients with relapsing breast cancer and soft tissue sarcoma have completed enrollment. Two Phase II studies investigating the activity of Incel in combination with chemotherapy for the treatment of small cell lung cancer and ovarian cancer are ongoing. 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 prostate cancer that is refractory to chemotherapy.
Related Link: Vertex Pharmaceuticals Incorporated.
|
