Hycamtin(R) Shows Positive Results in First-Line

Combination Therapy for Patients with Ovarian Cancer ATLANTA (PROTEXT) - New study results demonstrate thattreatment with SmithKline Beecham's Hycamtin(R) (topotecanhydrochloride for injection) and cisplatin followed by treatmentwith paclitaxel and cisplatin shows activity as first-linetherapy in patients suffering from advanced epithelial ovariancancer (E0C). The results, presented this week at the 35th annualmeeting of the American Society for Clinical Oncology (ASCO),showed an 81 percent response rate in patients treatedsequentially with Hycamtin and cisplatin, followed by cisplatinand paclitaxel. Hycamtin is indicated for use in metastaticcarcinoma of the ovary after failure of initial or subsequentchemotherapy and in the United States, Canada, Switzterland andAustralia for the treatment of small cell lung cancer sensitivedisease after failure of first-line chemotherapy. Hycamtin is notcurrently indicated for first-line ovarian cancer therapy. The study, presented by Paul Hoskins, M.D., for the NationalCancer Institute of Canada Clinical Trials Group, was designed toassess the efficacy and safety of the combination of Hycamtin andcisplatin in sequence with cycles of cisplatin and paclitaxel inpatients with advanced epithelial ovarian cancer, a disease whichis rarely curable. More than 28,000 women are diagnosed withovarian cancer in the Eurpoean Community each year. EOC accountsfor 85 to 90 percent of ovarian cancers. "There is a critical need to identify new agents that can beused to treat advanced EOC. These pilot data show that by addingHycamtin to the current standard therapy of cisplatin andpaclitaxel, we can achieve high clinical response rates," saidElizabeth Eisenhauer, M.D., Director, Investigational New DrugProgram, National Cancer Institute of Canada, Clinical TrialsGroup, Queens University in Ontario. "This approach allows theincorporation of an additional active agent in the treatment ofpatients with ovarian cancer but needs further evaluation beforewe can know if it leads to improved outcomes." In this phase II study, patients with advanced EOC receivedcisplatin 50 mg/m squared intravenously on day one and Hycamtin.75 mg/m squared intravenously over 30 minutes daily for fivedays for four 21-day cycles, followed by paclitaxel 135 mg/msquared over 24 hours on day one and cisplatin 75 mg/m squared onday two for four cycles. Of the evaluable patients who completedtreatment (n=36), 81 percent responded to treatment, confirmed bysecond-look surgery. In addition, 64 percent of evaluablepatients who began the study (n=39) had CA 125 normalization (acommon ovarian cancer market) during the first four cycles ofHycamtin and cisplatin, indicating positive responses to thetreatment. The non-hematologic toxicity was primarily grade 1/2.Non-hematologic grade 3/4 toxicities were primarilygastrointestinal (i.e., nausea, loss of appetite, constipation).Eighty-six percent of patients experienced grade 3/4 neutropeniawhile receiving the Hycamtin cisplatin combination. Dosereductions for topotecan were required in 12 percent of coursesand the treatment was delayed in 46 percent of courses. Ovarian Cancer Ovarian cancer is the most lethal of all gynecologicalcancers, killing more women each year than all othergynecological malignancies combined. Ovarian cancer starts in theovary, the female reproductive organ that is the main source ofthe hormones estrogen and progesterone. There are three maintypes of ovarian tumors, each named for the type of cells theystart from. EOC starts in the epithelial cells, which are thecells that cover the surface of the ovary. Most ovarian cancersare of this type. Women who are at a higher risk for ovarian cancer includewomen over 60, women who have never had children and women whohave been diagnosed with breast, intestinal or rectal cancer. Ifdiagnosed and treated at an early stage, the five-year survivalrate from ovarian cancer is 90 percent. However, the five-yearsurvival rate for all stages combined is 42 percent because only23 percent of cases are detected at an early stage. A Novel Mechanism of Action In November 1996, Hycamtin was the first topoisomerase Iinhibitor to be cleared for marketing by the European MedicinesEvaluation Agency (EMEA) and is indicated for the treatment ofpatients with recurrent, metastatic ovarian cancer. This class ofdrugs kills cancer cells by inhibiting the enzyme topoisomeraseI, an enzyme that is essential in the replication of DNA in humancells. Hycamtin is currently approved for second-line treatment ofovarian cancer in the 15 European Union (EU) member countries.Hycamtin has been studied in over 200 clinical trials and iscurrently under clinical investigation for, a number of othercancers including small cell lung cancer, non-small cell lungcancer, colorectal cancer, as well as lymphoma, myeloma andleukemia, breast cancer and pediatric cancers. SmithKline Beecham -- one of the world's leading healthcarecompanies -- discovers, develops, manufactures and marketspharmaceuticals, vaccines, over-the-counter medicines and health-related consumer products, and provides healthcare servicesincluding clinical laboratory testing and disease management. Forcompany information, visit SmithKline Beecham on the World WideWeb at http://www.sb.com. ots Original Text Service: SmithKlineBeecham Internet: http://www.newsaktuell.de Contact: LynneSmith, 44-181-975-2661, or Maria Favorito, 212-598-2807, both forSmithKline Beecham Company News On-Call:http://www.prnewswire.com/comp/801350.html or fax, 800-758-5804,ext. 801350 Web site: http://www.cohnwolfe.com Web site:http://www.sb.com

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