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Study Demonstrates That Xeloda Is Equivalent To Standard of Care in Adjuvant Colon Cancer

NEW ORLEANS, June 6 /PRNewswire/ -- Xeloda, an oral tablet, could replace the most widely-used intravenous (IV) chemotherapy for colon cancer, according to new results from a large international Phase III study presented today at the 40th annual American Society of Clinical Oncology (ASCO) meeting.

The X-ACT (Xeloda in Adjuvant Colon Cancer Therapy) study successfully met its primary endpoint in demonstrating that disease-free survival(1) for Xeloda is at least equivalent to intravenous 5-fluorouracil/leucovorin (5-FU/LV), also known as the Mayo Clinic Regimen, in the adjuvant treatment of Stage III colon cancer patients (or patients whose cancer has spread to the lymph nodes). The results show that treatment with Xeloda produced a 13 percent reduction in the risk of disease relapse or death from any cause when compared to intravenous 5-FU/LV. Xeloda also caused significantly fewer serious side effects, such as neutropenia and stomatitis compared to 5-FU/LV.

Hand-and-foot syndrome -- a common toxicity seen with fluoropyrimidines -- was significantly higher in the Xeloda arm in this study.

"This data shows the significant potential of Xeloda to treat more patients with early stage colon cancer," said Professor Jim Cassidy, Cancer Research UK Professor of Oncology and Chair of Medical Oncology, Beatson Oncology Centre, and University of Glasgow in Glasgow, Scotland, and presenter of the X-ACT data at ASCO. He also said, "The results of the trial further justify the ongoing and planned adjuvant studies of Xeloda in combination with other chemotherapies and targeted therapies in the treatment of colorectal cancer."

While intravenous 5-FU/LV regimens have been the foundation of colon cancer treatment for 40 years, researchers have long noted the need for more convenient treatment regimens. Intravenous therapy for colon cancer negatively impacts patient convenience: the Mayo Clinic Regimen typically requires at least 30 clinic visits over the 24-week treatment course, compared to a minimum of eight visits for patients receiving Xeloda.

Xeloda is currently indicated as first-line treatment of patients with metastatic colorectal cancer when treatment with fluoropyrimidine therapy alone is preferred. The X-ACT results will be submitted to the U.S. Food and Drug Administration to support the use of Xeloda in the adjuvant treatment setting later this year.

Highlights from the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT)

This international, randomized, open-label efficacy and safety study evaluated 1,987 patients receiving 24 weeks of treatment with either Xeloda 1250 mg/m2, twice daily on days 1-14 of a three week cycle (n=1004), or intravenous bolus 5-FU 425 mg/m2 with intravenous leucovorin 20 mg/m2 on days 1-5, repeated every 28 days (n=983) was accrued over a three-year period.

The primary endpoint of the study was to show that Xeloda's disease-free survival was at least equivalent to intravenous 5-FU/LV. Relapse-free survival(2) rates for Xeloda (a secondary endpoint of the trial) were statistically superior. The three-year relapse free survival rates were 65.5 percent for patients treated with Xeloda, compared to 61.9 percent treated with 5-FU/LV. This analysis measures the number of patients who remained disease-free at three years or who did not die as a result of their colon cancer or their treatment. The difference between the arms of the study translates into a 14 percent reduction in risk of relapse from colon cancer among patients treated with Xeloda (p=0.041). The benefits seen in the entire patient population were also maintained in patients over 70 years of age -- a patient group less likely to receive optimal treatment.

"These findings have the potential to bring a change to the current standard of adjuvant treatment for colon cancer because they show that a convenient oral regimen can be used in place of hours of cumbersome chemotherapy," said Dr. Howard Burris of the Sarah Cannon Cancer Center, Nashville, Tennessee, and investigator in the X-ACT Study.

Further, safety analysis showed that patients treated with Xeloda experienced significantly fewer severe (grade 3/4) toxicities, including less stomatitis and neutropenic fever/sepsis when compared to those receiving intravenous 5-FU/LV. Another study finding indicated that treatment with Xeloda was tolerated similarly by patients under and over age 65; furthermore, both age groups experienced a similarly low incidence of severe toxicities. Hand-and-foot syndrome -- a common toxicity seen with fluoropyrimidines -- was significantly higher in the Xeloda arm in this study.

"Since colon cancer is most often diagnosed in older patients, it is important to understand the effectiveness and safety of treatments in this age group," stated Carolyn Aldige, president of the Cancer Research and Prevention Foundation. "Because older Americans often do not always receive optimal treatment for their disease, these findings reinforce the importance of safe and effective agents for this population."

About Colon Cancer and Adjuvant Treatment

Colorectal cancer -- cancer of the colon or rectum -- is the second- leading cause of cancer-related deaths in the United States, with the American Cancer Society estimating that approximately 57,000 people die of the disease annually. The SEER Cancer Statistics Review estimates 106,370 colon cancer cases will be diagnosed in 2004. Benchmarks provided in the National Cancer Data Base (NCDB) show approximately 24,000 new patients will be diagnosed with Dukes' C colon cancer, the specific type and stage of the disease studied in X-ACT. Adjuvant treatment (chemotherapy following surgery) is one of the most common treatment strategies in patients diagnosed during the later stage of the disease.

About Xeloda

Xeloda is currently 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 over 5-FU/LV has not been demonstrated with Xeloda monotherapy. Use of Xeloda instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the survival advantage. The most common treatment-related side effect experienced in the patients receiving Xeloda was hand-foot syndrome, a skin condition that in metastatic colorectal cancer studies has been effectively managed through patient education, treatment interruption and, if necessary, dose reduction.

Xeloda is covered by Medicare. Xeloda Safety Information

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 prothrombin time (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.

Xeloda is contraindicated in patients who have a known hypersensitivity to 5-fluorouracil, and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. Xeloda is contraindicated in patients with severe renal impairment. For patients with moderate renal impairment, dose reduction is required.

The most common adverse events (greater than or equal to 20%) of Xeloda monotherapy were anemia, diarrhea, hand-and-foot syndrome, nausea, fatigue, vomiting, hyperbilirubinemia, dermatitis, stomatitis, anorexia, paresthesia, abdominal pain, lymphopenia, neutropenia and thrombocytopenia.

When Xeloda was combined with docetaxel, additional common adverse events (greater than or equal to 20%) included leukopenia, alopecia, edema, pyrexia, asthenia and constipation. Adverse events were more common in patients 80 years of age receiving monotherapy; and in patients 60 years of age receiving combination therapy. Patients with severe diarrhea should be carefully monitored.

As with any cancer therapy, there is a risk of side effects, and these are usually manageable and reversible with dose modification or interruption. Visit http://www.xeloda.com/ or call Roche at 800-526-6367 for full prescribing information.

(1) Disease-free survival: Relapse/new occurrence of disease due to colon cancer and all deaths. (2) Relapse-free survival: Relapse/new occurrence of disease due to colon cancer and/or treatment.

Source: Roche

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