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The Journal Of Clinical Oncology Publishes Phase III Clinical Study Using Oral Chemotherapy Xeloda (Capecitabine) In Combination With Taxotere (Docetaxel) For Metastatic Breast Cancer

Xeloda With Taxotere is the First Breast Cancer Combination Treatment To Demonstrate Survival Advantage

NUTLEY, NJ -- June 14, 2002 -- The June 15^th issue of the Journal of Clinical Oncology features a phase III clinical study about the use of Roche's XelodaŽ (capecitabine), an oral chemotherapy, in combination with Aventis' TaxotereŽ (docetaxel) for Injection Concentrate, given by infusion, for the treatment of metastatic breast cancer. The U.S. Food and Drug Administration recently approved the use of Xeloda in combination with Taxotere for the treatment of metastatic breast cancer based on the data from this phase III trial.

The results of this phase III study demonstrate that the combination of Xeloda and Taxotere provides a statistically significant survival benefit compared to Taxotere monotherapy (median 14.5 months vs. 11.5 months, log rank p= 0.0126). The survival advantage is a 23 percent less risk of death with Xeloda and Taxotere in combination compared to Taxotere alone (Hazard Ratio=0.775).

In addition, the study also shows a statistically significant superior objective tumor response of 42 percent for patients treated with the combination of Xeloda + Taxotere, compared to Taxotere monotherapy (30 percent, p=0.006). Time to disease progression is significantly longer for patients treated with Xeloda+Taxotere: median 6.1 months vs. 4.2 months with Taxotere alone (p=0.0001, Hazard Ratio=0.652), which translates into a 35 percent risk reduction for tumor progression in patients treated with Xeloda+Taxotere compared to Taxotere alone.

"We believe that the survival advantage of the combination of Xeloda+Taxotere may benefit many patients with metastatic breast cancer," said Georges Gemayel, Vice President, National Specialty Care Business Operation, at Roche.

This phase III study involved 511 patients with locally advanced or metastatic breast cancer and compared Xeloda in combination with Taxotere to Taxotere alone. The study endpoints included overall survival, time to disease progression and tumor response rate. Women with metastatic breast cancer whose anthracycline treatment had failed were randomized into either combination (oral Xeloda - 1250mg/m˛ twice daily, days 1-14 with one week of rest - plus i.v. Taxotere - 75mg/m˛, day 1 of each 21 day treatment cycle) or monotherapy (i.v. Taxotere 100mg/m˛, day 1 of each 21-day treatment cycle) groups.

"The combination of Xeloda and Taxotere is a major advancement in treating women with metastatic breast cancer, due in large part to the significant survival advantage observed with the combination," said Joyce O'Shaughnessy, M.D., Co-Director of breast cancer research at Baylor-Sammons Cancer Center and US Oncology. "This represents a crucial development, as improvements in patient survival are the bottom line, and the data from this study show early and consistent benefits for women treated with Xeloda and Taxotere, including survival, overall response rates and time to disease progression."

Breast cancer is the second most common cancer among women in the U.S., and approximately 203,500 new cases are expected this year. One in nine women in the U.S. will develop breast cancer in her lifetime. This year, a new case of breast cancer will be diagnosed every three minutes. Only 5-10 percent of breast cancers are due to heredity. This year alone, an estimated 39,600 women will die of breast cancer.

About Xeloda
Xeloda is an oral drug that is enzymatically converted into the cancer- fighting substance 5-FU. The enzyme thymidine phosphorylase (TP), occurs at higher levels at the site of the tumor than surrounding normal tissue. This finding has not been adequately studied in the clinical setting.

About Xeloda Monotherapy

Metastatic Colorectal Cancer:
Xeloda is indicated as first-line treatment of patients with metastatic colorectal cancer when treatment with fluoropyrimidine therapy alone is preferred. Combination chemotherapy has shown a survival benefit compared to 5-FU/LV alone. A survival benefit has not been demonstrated with Xeloda monotherapy as with the combination chemotherapy in colorectal cancer. Use of Xeloda instead of 5-FU/LV combinations has not been adequately studied to assure safety or preservation of the survival advantage.

Metastatic Breast Cancer:
Xeloda is also indicated for the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated. Resistance is defined as progressive disease while on treatment, with or without an initial response, or relapse within six months of completing treatment with an anthracycline-containing adjuvant regimen.

Xeloda is covered by Medicare.

To further improve patient safety, Roche submitted data from a clinical trial that confirmed an interaction between Xeloda and warfarin. To heighten physicians' awareness, Roche has agreed with the FDA to make the Xeloda and warfarin interaction information in a black box warning statement and support an ongoing program for physician and patient awareness of the potential interaction between Xeloda and coumarin derivative anticoagulants, such as warfarin.

Xeloda Safety Information
Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly. A clinically important drug interaction between XELODA and warfarin has been demonstrated; altered coagulation parameters and/or bleeding and death have been reported. Clinically significant increases in PT and INR have been observed within days to months after starting Xeloda, and infrequently within one month of stopping Xeloda. For patients receiving both drugs concomitantly, frequent monitoring of INR or PT is recommended. Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.

The most common adverse events (? 20%) of Xeloda in combination with docetaxel were lymphocytopenia, leukopenia, neutropenia/granulocytopenia, anemia, diarrhea, stomatitis, hand-and-foot syndrome, nausea, alopecia, thrombocytopenia, vomiting, edema, abdominal pain, pyrexia, asthenia, fatigue, constipation, and hyperbilirubinemia. Adverse events were more common in patients ? 60 years of age. Patients with severe diarrhea should be carefully monitored. Xeloda is contraindicated in patients who have a known hypersensitivity to 5-fluorouracil, and in patients with severe renal impairment. For patients with moderate renal impairment, dose reduction is required. As with any cancer therapy, there is a risk of side effects, and these are usually manageable and reversible with dose modification or interruption.

To further evaluate the role of Xeloda in breast and colorectal cancer in addition to numerous other solid tumors, there are multiple clinical trials currently on-going and planned. For further information on Xeloda, please visit http://www.xeloda.com or call Roche at 800-526-6367 for full prescribing information.

Xeloda is a registered trademark of Hoffmann-La Roche Inc.

About Taxotere
Taxotere, a drug in the taxoid class of chemotherapeutic agents, inhibits cancer cell division by essentially "freezing" the cell's internal skeleton, which is comprised of microtubules. Microtubules assemble and disassemble during a cell cycle. Taxotere promotes their assembly and blocks their disassembly, thereby preventing cancer cells from dividing and resulting in cancer cell death. Taxotere is currently approved in the United States to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy, and patients with locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy. According to Aventis, the most common severe side effects associated with Taxotere include low blood cell count, fatigue, fluid retention and mouth sores.

The most common non-severe side effects included hair loss, neurosensory, cutaneous, nail changes, nausea and diarrhea. These side effects are generally reversible and manageable. A premedication regimen with corticosteroids is recommended in order to prevent or reduce hypersensitivity and fluid retention. Taxotere is not appropriate therapy for patients with significant liver impairment or a low white blood cell count. Visit http://www.taxotere.com or http://www.aventisoncology.com for complete Taxotere prescribing information, including boxed WARNING.

About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. prescription drug unit of the Roche Group, a leading research-based health care enterprise that ranks among the world's leaders in pharmaceuticals, diagnostics and vitamins. Roche discovers, develops, manufactures and markets numerous important prescription drugs that enhance people's health, well-being and quality of life. Among the company's areas of therapeutic interest are: dermatology; genitourinary disease; infectious diseases, including influenza; inflammation, including arthritis and osteoporosis; metabolic diseases, including obesity and diabetes; neurology; oncology; transplantation; vascular diseases; and virology, including HIV/AIDS and hepatitis C.

For more information on the Roche pharmaceuticals business in the United States, visit the company's web site at: http://www.rocheusa.com

Taxotere is manufactured by Aventis.


SOURCE: Hoffmann-La Roche Inc.

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