Public Release: 

Updated data compares DOXIL (R)/CAELYX (TM) (doxorubicin HCl liposome injection) to Topotecan

Researchers present data in women with recurrent epithelial ovarian cancer

Sensei Health

Bridgewater, NJ, November 4, 2003 - Researchers have presented updated data comparing DOXIL®/CAELYX™ (doxorubicin HCl liposome injection) to topotecan HCl in patients with recurrent ovarian cancer. These data, from a randomized, controlled, multi-center, open-label, Phase III clinical study, were presented during a poster session at the 12th meeting of the Federation of European Cancer Societies (ECCO 12) in Copenhagen, Denmark.1

The National Cancer Institute estimates that in 2003, 25,000 American women will be diagnosed with ovarian cancer, and 14,000 women will die from it.2 This analysis compared DOXIL and topotecan - another common treatment for recurrent ovarian cancer - in epithelial ovarian cancer patients whose disease recurred after or did not respond to first-line, platinum-based chemotherapy. The primary objective of this long-term follow up analysis was to measure the overall survival and progression-free survival of these patients.

Researchers reported the median overall survival was three weeks longer for patients treated with DOXIL compared to those treated with topotecan (63 and 60 weeks, respectively, HR 0.82 [95 percent CI = 0.68 to 1.00]; p = 0.05). In addition, the overall progression-free survival was 16.1 weeks for DOXIL compared to 17.0 weeks topotecan (HR 0.88 [95 percent CI = 0.73 to 1.06]; p = 0.171).

Among platinum-sensitive patients (those who had a PFS interval of greater than six months after first-line, platinum-based chemotherapy), the median survival of patients receiving DOXIL was 112 weeks versus 77 weeks for patients receiving topotecan (HR 0.63 [95 percent CI = 0.47 to 0.85]; p = 0.002). DOXIL patients also saw a significant advantage in median PFS versus those receiving topotecan (28.9 and 23.1 weeks, respectively, HR = 0.76 [95 percent CI = 0.58 to 1.00]; p = 0.046).

In the subset of patients with platinum-refractory disease (those whose disease progressed during initial platinum-based chemotherapy, demonstrated stable disease or relapsed within six months after completing platinum-based chemotherapy), median survival was similar in the two treatment groups (36 weeks for DOXIL and 41 weeks for topotecan, HR = 1.01 [95 percent CI = 0.78 to 1.31]; p = 0.943), as was PFS (median 9.4 and 13.6 weeks respectively, HR = 1.00 [95 percent CI = 0.77 to 1.29]; p = 0.983).

"These updated results provide important information in terms of future research directions and treatment options in recurrent epithelial ovarian cancer," commented Alan N. Gordon, M.D., Director of Research in Gynecology for US Oncology, and lead author of the study.

In the study, a total of 474 patients were randomly assigned to receive either DOXIL 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). A total of 239 patients received DOXIL; 235 patients received topotecan. This analysis was performed after 90 percent of the subjects either had died or were lost to follow-up. An analysis of these data was first published in the July 15, 2001 edition of the Journal of Clinical Oncology.3

No signs or symptoms of congestive heart failure were reported in either treatment group. Severe hematologic toxicities for DOXIL and topotecan, respectively, included neutropenia (an abnormal decrease in the number of neutrophils, a type of white blood cell; 35 percent vs. 81 percent), anemia (reduced red blood cell count; 35 percent vs. 72 percent), thrombocytopenia (low platelet count; 13 percent vs. 65 percent) and leukopenia (low white blood cell count; 36 percent vs. 64 percent).

Additionally, alopecia (hair loss) was reported in 16 percent of DOXIL-treated patients and in 49 percent 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 percent of DOXIL-treated patients and in one percent of topotecan-treated patients. The incidence of stomatitis (inflammation of the oral mucosa) was 40 percent for DOXIL and 15 percent for topotecan. Most patients were able to continue therapy with dose modification, symptomatic therapy or both.

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

About Ovarian Cancer and DOXIL
Ovarian cancer is the most deadly form of gynecologic cancer. Roughly 75 percent of women with ovarian cancers are not diagnosed until the disease reaches advanced stages and is more difficult to manage.4 As a result, approximately 31 percent of patients with advanced disease survive as long as five years.5

DOXIL is an advanced form of doxorubicin, a liposomal formulation of doxorubicin, which means that doxorubicin is encapsulated by a coating made up of fatty bubbles, called liposomes. Through a process known as pegylation, the liposomes are coated with a layer of hair-like strands made from methoxypolyethylene glycol (MPEG). Pegylation helps protect the drug from the immune system, resulting in the product circulating in the blood for a longer period of time. The longer circulation allows dosing once every four weeks.

DOXIL is indicated for the treatment of metastatic carcinoma of the ovary in patients with disease that is refractory to both paclitaxel- and platinum-based chemotherapy regimens. Refractory disease is defined as disease that has progressed while on treatment, or within six months of completing treatment. DOXIL also is indicated for the treatment of AIDS-related Kaposi's sarcoma in patients with disease that has progressed on prior combination chemotherapy or in patients who are intolerant to such therapy.

These indications are based on objective tumor response rates. No results are available from controlled trials that demonstrate a clinical benefit resulting from this treatment, such as improvement in disease-related symptoms or increased survival.

In clinical trials, the most common side effects reported with DOXIL therapy included reduced red blood cell count (anemia), reduced white blood cell count (neutropenia), nausea, hand-foot syndrome, mouth sores (stomatitis), weakness, vomiting, rash, mild hair loss, constipation, appetite loss, diarrhea, and tiredness. Some patients experienced infusion-related reactions and skin reactions. Hand-foot syndrome, also known as PPE, is characterized by symptoms of swelling, pain, redness and, for some patients, peeling of the skin on the hands and feet; in 17 percent of patients, these symptoms were moderate to severe. In some patients, heart-related side effects were reported, some of which were severe. Due to the serious, potentially permanent effects of some of these events, including the potential for bone marrow suppression, close monitoring is necessary.

Experience with DOXIL at high cumulative doses is too limited to have established its effects on the myocardium. Therefore, it should be assumed that DOXIL will have myocardial toxicity similar to conventional formulations of doxorubicin HCl. DOXIL should be administered to patients with a history of cardiovascular disease only when the benefit outweighs the risk. Acute infusion-associated reactions have occurred in up to 10 percent of patients treated with DOXIL. Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have been reported. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. Severe myelosuppression may occur. Dosage should be reduced in patients with impaired hepatic function. Accidental substitution of DOXIL for doxorubicin HCl has resulted in severe side effects. DO NOT SUBSTITUTE. The use of DOXIL should be limited to physicians experienced in the use of cancer chemotherapeutic agents.

DOXIL® (doxorubicin HCl liposome injection) is marketed in the United States by Ortho Biotech Products, L.P. and in Israel by Janssen-Cilag. Schering-Plough Pharmaceuticals, under a licensing agreement, markets CAELYX™ throughout the rest of the world.

For more information about DOXIL, please visit www.DOXIL.com.

Full prescribing information for DOXIL is available at http://www.doxil.com/05_shared_pages/01_prescribing_info.html.com.

About Ortho Biotech Products, L.P.
Ortho Biotech Products, L.P., marketer of DOXIL, was established in Raritan, New Jersey in 1990 as the first biotechnology subsidiary of Johnson & Johnson. Since that time, Ortho Biotech and its worldwide affiliates have earned a global reputation for researching, manufacturing and marketing innovative healthcare products that extend and enhance the quality of patients' lives. Ortho Biotech, now headquartered in Bridgewater, New Jersey, is committed to leading the fight against cancer. Additionally, the company markets drugs for the treatment of anemia associated with chronic illnesses, a rare form of leukemia, life-threatening fungal infections and organ transplant rejection.

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, September 22, 2003 (poster).

2National Cancer Institute. SEER Cancer Statistics Review 1975-2000. Table I-1: Estimated new cancer cases and deaths for 2003.

3Gordon AN, Fleagle JT, Guthrie D, et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 2001;19:3312-3322.

4American Cancer Society. Cancer Facts & Figures 2003. Pages 15-17.

5Idem.

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