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Trisenox, ATRA Combination Produces High Remission Rates in Acute Promyelocytic Leukemia

SAN DIEGO, Dec. 9 /PRNewswire-FirstCall/ -- In two separate presentations at the 45th Annual Meeting of the American Society of Hematology (ASH), data were provided on arsenic trioxide in combination with an analog of vitamin A, all-trans retinoic acid (ATRA), that showed complete response (CR) rates in excess of 90 percent with newly diagnosed or previously untreated APL. APL is a rare and potentially fatal form of leukemia that afflicts approximately 1,500 to 2,000 people each year in the United States. Cell Therapeutics, Inc. (CTI) (NASDAQ:CTIC) markets TRISENOX (arsenic trioxide) in the United States and Europe for the treatment of relapsed or refractory APL.

The first study (Poster session abstract #2283) included 20 patients with newly diagnosed APL who were treated with ATRA (45 mg/m2) daily and TRISENOX (0.15 mg/kg) beginning at day 10 of treatment. According to the protocol, patients who had an elevated white blood cell count (WBC >10,000) or who did not achieve molecular remission within a certain timeframe were given gemtuzumab (9mg/m2). Approximately half of the patients received gemtuzumab in addition to the TRISENOX and ATRA combination. Eighteen patients (90 percent) achieved a CR within an average of 28 days of starting treatment. Fifteen patients with results available at the time of presentation, were PCR positive at the time of CR. PCR positive patients are patients who have not achieved a molecular remission. One patient has relapsed, 11 of the PCR positive patients achieved molecular, remission becoming PCR negative on TRISENOX and ATRA and ten remain PCR negative at a median of ten months from CR. In general therapy was well tolerated with manageable side effects consistent with those expected of ATRA and TRISENOX and with no increased toxicity from the combination.

"This front-line trial of TRISENOX in combination with ATRA was conducted to determine if TRISENOX could minimize or eliminate the need for standard chemotherapy," noted Elihu Estey, M.D., of The University of Texas, M. D. Anderson Cancer Center, an investigator on one of the trials. "Due to the long-term side effects, such as heart failure or secondary leukemias, reported with the use of standard anthracycline chemotherapy, the combination of these two active agents in this disease makes good clinical sense. These results support the potential for TRISENOX as a front-line treatment of APL. The CR rate is similar to what we have observed with standard therapy and the high rate of PCR negativity is noteworthy."

The second study (Oral session abstract #486) randomized 61 patients with previously untreated APL to receive either ATRA, arsenic trioxide or the combination of ATRA plus arsenic trioxide. While the CR rate in each arm was high (greater than or equal to 90 percent), the combination of arsenic trioxide and ATRA resulted in better clinical and molecular remission than the monotherapy arms. Patients on the combination arm achieved CR faster (median 26 days) than the ATRA arm (median 41 days) or arsenic trioxide arm (median 31 days). With a median follow up of 15 months, all 20 patients (100 percent) in the combination ATRA plus arsenic trioxide therapy arm remained in CR whereas seven of 37 patients in the monotherapy arms relapsed (p In two additional presentations, one on TRISENOX(R) as a front-line treatment in pediatric patients with APL (Poster session abstract #2288) and another testing TRISENOX(R) as a consolidation therapy in adults with APL (Poster session abstract #2287), use of TRISENOX(R) either reduced or eliminated the need for anthracycline-based therapy. In the pediatric population of patients, TRISENOX(R) was shown to produce nine of 10 hematologic remissions (90 percent) at a mean duration of 49 days (range: 41-60) with no significant short-term side effects.

Arsenic trioxide was also prominently featured by Zhen-yi Wang, M.D., of the Shanghai Institute of Hematology, in the Ham-Wasserman lecture on Saturday, Dec. 6, in his presentation entitled, "Treatment of Acute Leukemia by Inducing Differentiation and Apoptosis."

About TRISENOX(R)
TRISENOX(R) (arsenic trioxide) is marketed by Cell Therapeutics, Inc. (CTI). TRISENOX(R) was approved for marketing in 2000 by the U.S. Food and Drug Administration to treat patients with relapsed or refractory Acute Promyelocytic Leukemia (APL), a rare, life-threatening form of cancer of the blood. TRISENOX(R) was granted marketing authorization from the European Commission in March 2002. APL, one of eight subtypes of acute myeloid leukemia (AML), represents 10-15 percent of the more than 20,000 patients diagnosed with AML each year. TRISENOX(R) is currently being studied in more than 40 clinical trials in a variety of cancers.

U.S. marketing approval for TRISENOX(R) was granted based on results from a U.S. multicenter study in which 40 relapsed APL patients were treated with TRISENOX(R) 0.15 mg/kg until bone marrow remission or a maximum of 60 days. Thirty-four patients (85 percent) achieved CR. When the results for these 40 patients were combined with those for the 12 patients in a pilot trial, an overall response rate of 87 percent was observed.

WARNING: TRISENOX(R) should be administered under the supervision of a physician who is experienced in the management of patients with acute leukemia. Some patients with acute promyelocytic leukemia (APL) treated with TRISENOX(R) have experienced APL differentiation syndrome -- with symptoms similar to retinoic acid-acute promyelocytic leukemia (RA-APL) syndrome. Arsenic trioxide can cause QT prolongation (which can lead to torsade de pointes) and complete atrioventricular block.

The most common adverse events associated with TRISENOX(R) have been generally manageable, reversible and usually did not require interruption of therapy. These have included hypokalemia, hypermagnesemia, hyperglycemia and thrombocytopenia as reported in 13 percent of the patients (n=40). Abdominal pain, dyspnea, hypoxia, bone pain and neutropenia were reported in 10 percent of these patients, while arthralgia, febrile neutropenia and disseminated intravascular coagulation were reported in eight percent of patients.

Source: Cell Therapeutics, Inc.

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