To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Doxil (Liposomal Doxorubicin) Shows Potential In Recurrent Ovarian Cancer URL: http://www.pslgroup.com/dg/201F52.htm Doctor's Guide July 26, 2001
RARITAN, NJ -- July 26, 2001 -- A study featured in the current issue of The Journal of Clinical Oncology compares Doxil® (liposomal doxorubicin HCl) with topotecan, another common treatment for recurrent ovarian cancer. The randomized, multi-center study, evaluating 474 patients at 104 research centers in the United States and Europe, is one of the largest conducted among women suffering from ovarian cancer. This study presents the results of a phase III clinical trial between Doxil and topotecan. Further studies will be required to establish the clinical benefit of Doxil. The objective of the study was to compare the efficacy and safety of Doxil versus topotecan in patients with epithelial ovarian carcinoma following failure of first-line, platinum-based chemotherapy. The primary endpoint of the study was to determine time to progression. The results of the study showed that median time to progression (overall progression-free survival) for Doxil was 16.1 weeks and 17.0 weeks for topotecan (p=0.095). Overall response rates for Doxil and topotecan were 19.7 percent and 17.0 percent, respectively (p=0.390). Doxil-treated patients survived an average of 60 weeks and topotecan-treated patients survived an average of 56.7 weeks. Doxil is indicated to treat metastatic ovarian cancer in women whose disease is refractory to paclitaxel- and platinum-based chemotherapy. This indication is 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. Refractory ovarian cancer is defined as disease that has progressed during treatment or within six months after completing treatment. As prospectively planned and outlined in the protocol's study analysis, the researchers conducted a subset analysis and found that Doxil-treated patients who were still responsive to platinum-based chemotherapy showed statistically significant increases in the length of survival time compared with topotecan treated patients (2.1 years versus 1.4 years, p=0.008). Platinum-sensitive patients demonstrated a significant improvement in progression-free survival (p=0.037) with Doxil, 28.9 weeks versus 23.3 weeks. Response rates of 28.4 percent (Doxil) and 28.8 percent (topotecan) were not statistically different (p=0.964). The platinum-refractory subgroup demonstrated a non-statistically significant survival trend in favor of topotecan (p=0.733). Response rates and times to progression in this subgroup were not statistically different between the two treatment arms. These results suggest another trial is warranted to confirm these findings. "Treating women with advanced, recurring ovarian cancer is an incredible challenge," said Alan Gordon, M.D., Director of Gynecologic Research for U.S. Oncology at the Sammons Cancer Center, Baylor University Medical Center in Dallas. "Since up to 80 percent of ovarian cancer patients will relapse, physicians need treatment options for patients with refractory ovarian cancer." In the study, 77 percent of topotecan treated patients experienced NCI (National Cancer Institute) Common Toxicity Grade 3/4 (severe/life threatening) neutropenia, compared to 12 percent of Doxil treated patients. In the topotecan group, there were three deaths attributed to resulting infections, including neutropenia and sepsis. Seventeen percent of patients in the study's Doxil arm experienced grade 4 toxicities, and there were no treatment-associated deaths in the Doxil group. Grade 3/4 anemia occurred in 28 percent of the topotecan-treated group compared to 5 percent of the Doxil-treated group. Forty-nine percent of patients in the Doxil-treated group and 1 percent of patients in the topotecan-treated group experienced skin toxicities, specifically Palmar-plantar erthrodysesthesia or PPE. Forty percent of patients in the Doxil-treated group presented with mouth sores compared to 15 percent of those receiving topotecan. The side effects in the Doxil group were managed by lengthening the time between doses of Doxil. Doxil was administered via a single hour-long infusion once every 28 days; women treated with topotecan received daily 30-minute infusions for five days every 21 days. "Continuing clinical research is needed to define the therapeutic role Doxil can play in the treatment of advanced ovarian cancer," said Ed Schnipper, MD, vice president of clinical development at ALZA Corporation. "Dr. Gordon's study adds support to the role of Doxil as an additional choice for the treatment of women with refractory ovarian cancer." Doxil is a pegylated liposomal formulation of doxorubicin, an intravenous chemotherapy agent. Doxil uses a novel, targeted delivery system called Stealth® technology to help evade recognition and uptake by the immune system, so the liposomes can circulate in the body longer. 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, soreness of the mouth (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 Palmar-plantar erthrodysesthesia (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 about 5 percent to 10 percent of patients treated with Doxil. 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.
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