NUTLEY, N.J., June 29 /PRNewswire/ -- Landmark data published in this week’s prestigious New England Journal of Medicine show that Xeloda(R) (capecitabine) -- an innovative oral chemotherapy -- is an effective alternative to intravenous 5-FU/LV, which has been the foundation of adjuvant (post-surgical) treatment for patients with Dukes’ C colon cancer for 40 years.
According to the study’s authors, physicians and patients alike have long desired more convenient treatment options for colon cancer, provided efficacy is not compromised. Intravenous 5-FU/LV treatment for colon cancer, also known as the Mayo Clinic regimen, can require up to 30 clinic visits over the 24-week treatment course, compared to a minimum of eight visits for patients receiving Xeloda.
“Our research suggests that Xeloda is equivalent to the Mayo Clinic Regimen in the adjuvant treatment of colon cancer with improved convenience,” said Principal Investigator Chris Twelves, MD, University of Leeds and Tom Connors Cancer Research Centre in Bradford, United Kingdom.
Professor Jim Cassidy, Cancer Research UK Professor of Oncology and Chair of Medical Oncology, Beatson Oncology Centre, and University of Glasgow in Glasgow, Scotland, another of the lead investigators of the X-ACT trial agreed, commenting, “According to some recent studies, most patients with cancer would prefer a convenient oral chemotherapy if they did not have to sacrifice efficacy.”
In the accompanying NEJM editorial, authors Carmen Allegra, MD, and Daniel J. Sargent, Ph.D, also stated that “disease free survival, relapse-free survival (as distinguished from disease-free survival by the exclusion of deaths from causes other than colon cancer), and overall survival all numerically favored capecitabine (Xeloda), with Pvalues hovering close to 0.05.” [Note: Later data showed the overall survival Pvalue to be 0.169.]
Based on the X-ACT (Xeloda in Adjuvant Colon Cancer Therapy) trial, Xeloda recently received approval by the U.S. Food and Drug Administration (FDA) for the adjuvant treatment of patients with Dukes’ C colon cancer when fluoropyrimidine therapy alone is preferred. The pivotal data showed that Xeloda met its primary endpoint of non-inferiority to intravenous 5-FU/LV for disease-free survival (DFS). At this time, neither Xeloda nor combination chemotherapy has been shown to prolong overall survival; combination chemotherapy has demonstrated an improvement in disease-free survival compared to 5-FU/LV.
About the X-ACT Trial
Between 1998 and 2001, 1,987 patients (1,004 patients were randomly assigned to Xeloda; 983 were assigned to intravenous 5-FU/LV) were enrolled at 164 centers worldwide. As reported in the article, the primary aim of the study was to show equivalence in disease-free survival between Xeloda and intravenous 5-FU/LV. Secondary endpoints included relapse-free survival, overall survival and safety. The study was designed and initiated by investigators at and employees of the sponsor, F. Hoffmann-La Roche.
Key Study Findings
The study authors reported that the three-year disease-free survival rates were 64.2 percent for patients treated with Xeloda, compared to 60.6 percent treated with 5-FU/LV. The overall incidence of grade 3-4 toxicities were similar between Xeloda and 5-FU/LV. Patients treated with Xeloda experienced fewer severe (grade 3-4) toxicities for certain events including less stomatitis and neutropenic fever/sepsis when compared to those receiving intravenous 5-FU/LV. Hand-and-foot syndrome -- a common toxicity seen with fluoropyrimidines -- was higher in the Xeloda arm in this study (grade 3-4).
According to Dr. Howard Burris of the Sarah Cannon Research Institute in Nashville, Tennessee, and lead U.S. investigator of the X-ACT trial, “More early-stage colon cancer patients now have the option of being treated with an oral chemotherapy pill that can be taken at home, rather than with intravenous 5-FU/LV that has to be repeatedly administered in a clinic.”
About Colon Cancer and Adjuvant Treatment
Colorectal cancer (cancer of the colon or rectum) is the third leading cause of cancer-related deaths in the United States, and the second worldwide. The American Cancer Society (ACS) estimates that in 2005, more than 145,000 Americans will be diagnosed with colorectal cancer and more than 56,000 will die from the disease - a number that could be cut in half if Americans followed ACS recommendations to begin screening at age 50. 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 indicated as a single agent for adjuvant treatment in patients with Dukes’ C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. Xeloda was non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS). Although neither Xeloda nor combination therapy prolongs overall survival (OS), combination chemotherapy has been demonstrated to improve disease-free survival compared to 5-FU/LV. Physicians should consider these results when prescribing single-agent Xeloda in the adjuvant treatment of Dukes’ C colon cancer.
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. Xeloda can induce diarrhea, sometimes severe. Patients with severe diarrhea should be carefully monitored. Patients 80 and older receiving Xeloda monotherapy may experience a greater incidence of grade 3 or 4 adverse events. Xeloda may cause fetal harm when given to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Xeloda. It is recommended that nursing be discontinued when using Xeloda. Men should use birth control when using Xeloda.
Common adverse events in the adjuvant setting were: diarrhea (Xeloda 47%, 5-FU/LV 65%), nausea (Xeloda 34%, 5-FU/LV 47%), stomatitis (Xeloda 22%, 5-FU/LV 60%), vomiting (Xeloda 15%, 5-FU/LV 21%,), fatigue (Xeloda 16%, 5-FU/LV 16%) and hand-foot syndrome (Xeloda 60%, 5-FU/LV 9%). 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.
About Roche -- More Than a Century in the U.S. and the World
Founded in 1896 and headquartered in Basel, Switzerland, Roche is one of the world’s leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is one of the world’s leaders in diagnostics, the leading supplier of pharmaceuticals for cancer, as well as a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on many fronts to improve people’s health and quality of life. Roche employs roughly 65,000 people in 150 countries, including approximately 15,000 in the United States.
Roche’s U.S. operations celebrate their American Centennial in 2005. In another milestone this year, Roche was named in January to Fortune magazine’s list of Best Companies to Work for in America. One of an increasingly rare breed of major healthcare companies that still bear their original name, Roche today has more than a dozen U.S. sites located in California, Colorado, Indiana, New Jersey and South Carolina, as well as in Puerto Rico. Roche has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai. Roche’s Pharmaceuticals Division offers a portfolio of leading medicines in therapeutic areas including cancer, HIV/AIDS, hepatitis C, transplantation, dermatology and influenza. Roche’s Diagnostics Division supplies a wide array of innovative testing products and services to researchers, physicians, patients, hospitals and laboratories world-wide. For further information, please visit our worldwide and U.S. websites (Global: http://www.roche.com and U.S.: http://www.roche.us).
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CONTACT: Ginny Valenze of Roche, +1-973-562-2783, Cell: +1-973-943-9219,virginia.valenze@roche.com; or Noelle Boyd of Manning Selvage & Lee forRoche, +1-212-468-4313, Cell: +1-917-334-8662, noelle.boyd@mslpr.com