Roche Files for Application with the FDA to Market the Oral Cancer Drug Xeloda® for Adjuvant Treatment of Colon Cancer

NUTLEY, N.J. -- Roche has announced the submission of a supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration (FDA) to market Xeloda® (capecitabine) for the treatment of colon cancer after surgery (adjuvant therapy). Simultaneously, Roche also has filed with the European Medicines Agency (EMEA) to market Xeloda for this indication in the European Union. Xeloda is currently indicated as first-line treatment of patients with metastatic colorectal cancer when treatment with fluoropyrimidine therapy alone is preferred.

Lars Birgerson, MD, PhD, vice president of medical affairs, Roche U.S., said, "Roche is dedicated to continually looking for ways to advance cancer treatments. We will work closely with regulatory authorities to make Xeloda available as quickly as possible as a new, convenient oral option for patients in need of adjuvant treatment for their colon cancer."

The submission to the FDA is based on results from the landmark X-ACT trial (Xeloda in Adjuvant Colon Cancer Therapy), a global study of nearly 2,000 patients that was first presented in June at the American Society of Clinical Oncology (ASCO) Annual Meeting in New Orleans. The trial successfully met its primary endpoint in demonstrating that disease-free survival¹ for Xeloda is at least equivalent to intravenous 5-fluorouracil/ leucovorin (5-FU/LV) in the adjuvant treatment of Stage III colon cancer patients (or patients whose cancer has spread to the lymph nodes). The results also showed that treatment with Xeloda produced statistically superior relapse-free survival² rates (a secondary endpoint of the trial) and caused significantly fewer serious side effects (e.g., neutropenia and stomatitis) when compared to intravenous 5-FU/LV. Hand-and-foot syndrome -- a common side effect seen with fluoropyrimidines -- was significantly higher in the Xeloda arm in this study.

"I expect Xeloda to become a new standard of care in the treatment of adjuvant colon cancer, providing tremendous benefit for patients," said Dr. Howard Burris of the Sarah Cannon Cancer Center, Nashville, Tenn., and investigator in the X-ACT Study. "Not only have the data shown that Xeloda is at least as effective as the Mayo Clinic regimen (5-FU/LV), the current standard, but it also shows that a convenient oral regimen can be used in place of hours of cumbersome intravenous chemotherapy."

The results of the X-ACT study support ongoing and planned studies of the oral chemotherapy treatment Xeloda in combination with other chemotherapies and targeted therapies, enrolling more than 6,000 patients on a global level.

"Colon cancer kills 57,000 Americans each year. Researchers around the world have long noted the need for more effective and convenient treatment regimens. We commend this continuing commitment to research to effect improvement in the treatment of this preventable and treatable disease," stated Carolyn Aldige, president of the Cancer Research and Prevention Foundation.

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 percent) 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 percent) 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.

Source: Roche