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Longer Survival Time Seen With Pegylated Doxorubicin Versus Topotecan in Phase III Study

Copenhagen, Denmark, September 26/PRNewswire/ -- Schering-Plough Europe reported that researchers at the 12th meeting of the Federation of European Cancer Societies (ECCO 12)(1) presented data demonstrating that patients treated with CAELYX(TM)/DOXIL(R) (pegylated liposomal doxorubicin hydrochloride) showed a statistically significant increase in overall survival (OS) as compared to those treated with topotecan. These data were from a randomised, controlled, multicentre, open-label, Phase III clinical study.

In this Phase III study, the analysis compared CAELYX and topotecan -- another anticancer agent -- in epithelial ovarian cancer patients whose disease recurred after or did not respond to first-line, platinum-based chemotherapy. The objective of this long-term follow up analysis was to update the OS data for these patients.

Researchers reported that OS was statistically significantly longer for patients treated with CAELYX compared to those treated with topotecan (hazard ratio [HR] 0.82; p = 0.05). In addition, progression-free survival (PFS) also favoured CAELYX (HR 0.88; p = 0.17), although this was not statistically significant.

Among platinum-sensitive patients (those who had a PFS interval of greater than six months after first-line, platinum-based chemotherapy), the survival of patients receiving CAELYX was significantly longer than for patients receiving topotecan and this difference is highly significant (HR 0.63; p = 0.002). CAELYX patients in this subgroup also had a significant advantage in PFS vs. those receiving topotecan (HR = 0.76; p = 0.046).

In the subset of patients with platinum-refractory disease (those whose disease progressed during initial platinum-based chemotherapy or within six months after completing platinum-based chemotherapy), survival and PFS were similar in the two treatment groups.

"These updated results are consistent with previously reported data for pegylated liposomal doxorubicin and topotecan," commented Alan N. Gordon, M.D., Director of Research in Gynecology for US Oncology, and lead author of the study. "This study suggests that CAELYX is a valuable treatment option in patients with recurrent epithelial ovarian cancer."

In the study, 481 patients were randomly assigned to receive either CAELYX 50 mg/m2 every 28 days (up to six cycles) or topotecan 1.5 mg/m2/day for five consecutive days every 21 days (up to eight cycles), and 474 patients received study drug. A total of 239 patients received CAELYX; 235 patients received topotecan. This analysis was performed after 90 per cent of the patients either had died (n=199, CAELYX; n=214, topotecan) or were lost to follow up (n=11, CAELYX; n=9, topotecan). An analysis of these data was first published in the July 15, 2001, edition of the Journal of Clinical Oncology. (2)

No signs or symptoms of congestive heart failure were reported in either treatment group. Severe haematologic toxicities for CAELYX and topotecan, respectively, included neutropenia (an abnormal decrease in the number of neutrophils, a type of white blood cell; 35 per cent vs. 81 per cent), anaemia (reduced red blood cell count; 36 per cent vs. 72 per cent), thrombocytopenia (low platelet count; 13 per cent vs. 65 per cent) and leukopenia (low white blood cell count; 36 per cent vs. 63 per cent).

Additionally, alopecia (hair loss) was reported in 16 per cent of CAELYX-treated patients and in 49 per cent of those receiving topotecan. Hand-foot syndrome (also known as palmar-plantar erythrodysesthesia, or PPE), a skin reaction that usually occurs on the palms of the hands and the soles of the feet, was reported in 49 per cent of CAELYX-treated patients and in 1 per cent of topotecan-treated patients. The incidence of stomatitis (inflammation of the oral mucosa) was 40 per cent for CAELYX and 15 per cent for topotecan. Most patients were able to continue therapy with dose modification, symptomatic therapy or both.

This research was supported by Ortho Biotech Products, L.P.

CAELYX is currently marketed in the European Union (EU) as monotherapy for metastatic breast cancer in patients who are at increased cardiac risk. CAELYX is also marketed in the EU for the treatment of advanced ovarian cancer in women who have failed first-line, platinum-based therapy, and for the treatment of AIDS-related Kaposi's sarcoma in patients with low CD4 counts ( CAELYX is a long-circulating pegylated liposomal formulation of doxorubicin hydrochloride, a widely used cytotoxic agent. Cytotoxic agents are designed to prevent the replication of cells that divide rapidly, including those in tumours. Schering-Plough has exclusive ex-US marketing rights to CAELYX, except in Japan and Israel, through a distribution agreement with ALZA, a wholly-owned subsidiary of Johnson & Johnson of New Brunswick, N.J., USA. The product is marketed in the United States under the trade name DOXIL(R) by Ortho Biotech Products, L.P., a biotechnology subsidiary of Johnson & Johnson.

Schering-Plough Europe, based in Brussels, Belgium, is the European country operation of Schering-Plough Corporation (NYSE:SGP) of Kenilworth, N.J., USA, a research-based company engaged in the discovery, development, manufacturing and marketing of pharmaceutical products worldwide.

(1) Gordon AN, Teitelbaum A, and the 30-49 Study Group. "Overall Survival Advantage for Pegylated Liposomal Doxorubicin Compared to Topotecan in Recurrent Epithelial Ovarian Cancer." Presented at the 12th meeting of the Federation of European Cancer Societies (ECCO 12), Copenhagen, Denmark, Sept. 22, 2003 (poster).

(2) Gordon AN, Fleagle JT, Guthrie D, et al. "Recurrent epithelial ovarian carcinoma: a randomised phase III study of pegylated liposomal doxorubicin versus topotecan;" J Clin Oncol 2001;19:3312-3322.

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Source: Schering-Plough Europe

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