FDA Approves Capecitabine for Adjuvant Treatment of Colon Cancer
Jun 17, 2005 - 9:42:38 AM

Roche announced today that the U.S. Food and Drug Administration (FDA) has approved Xeloda(R) (capecitabine) -- an innovative oral chemotherapy -- for the adjuvant (post-surgery) treatment of patients with Dukes' C colon cancer.

Adjuvant chemotherapy is the standard treatment approach for Dukes' C colon cancer (cancer that has spread to the lymph nodes), where chemotherapy is given after the tumor has been surgically removed. This approval will now give patients who have undergone complete resection of their primary tumor the option of an oral chemotherapy when fluoropyrimidine therapy alone is preferred.

The adjuvant indication was based on data from the X-ACT (Xeloda in Adjuvant Colon Cancer Therapy) trial. This pivotal trial showed that Xeloda met its primary endpoint of non-inferiority to 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.

Although intravenous 5-FU/LV (also known as the Mayo Clinic Regimen) has been the foundation of such treatment for 40 years, researchers have long recognized the need for more convenient treatment regimens. The Mayo Clinic intravenous regimen for colon cancer can require up to 30 clinic visits over the 24-week treatment course, compared to a minimum of eight visits for patients receiving Xeloda.

"What this means is that now thousands of additional colon cancer patients could have the option of using a convenient and effective oral chemotherapy earlier in the treatment of their disease. With Xeloda, they can replace hours of cumbersome intravenous therapy in a clinic with a pill that can be taken at home," said Dr. Howard Burris of the Sarah Cannon Research Institute in Nashville, Tennessee. "This new indication for Xeloda is great news for colon cancer patients."

The three-year disease-free survival rates were 66 percent for patients treated with Xeloda, compared to 62.9 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).

Xeloda is a drug taken orally which is activated into a chemotherapy agent by a naturally-occurring enzyme called thymidine phosphorylase, or TP. Once in contact with TP, which is expressed at higher levels by colorectal cancers, Xeloda is transformed inside the tumor into 5-FU, an anti-cancer drug.

"Roche applauds the FDA's decision today. With this approval, even more colon cancer patients will have access to an oral treatment option in the adjuvant setting, and can benefit from the convenience of a proven, effective oral chemotherapy," said Lars Birgerson, M.D., Ph.D., Vice President, Medical Affairs, Roche U.S. "The approval underscores our ongoing commitment to advancing cancer treatment for all patients."

Roche has an ongoing study program looking at Xeloda in combination with other chemotherapies and targeted therapies.

"More than 145,000 Americans will be diagnosed with colon cancer this year, so it's important that the cancer community continually seeks to improve available treatment options," said Carolyn Aldige, president of the Cancer Research and Prevention Foundation. "We commend Roche's commitment, as evidenced by today's FDA approval, to bringing effective and more convenient options to patients with colon cancer."

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.

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