FDA Approves Capecitabine, First Oral Chemotherapy for the Treatment of Metastatic Colorectal Cancer

August 1, 2001

The US Food and Drug Administration (FDA) has approved capecitabine (Xeloda), the first oral chemotherapy for the

The US Food and Drug Administration (FDA) has approvedcapecitabine (Xeloda), the first oral chemotherapy for the treatment ofmetastatic colorectal cancer (the second leading cause of cancer mortality amongAmericans). Capectibine is only the second treatment for colorectal cancerapproved in the United States in the past 40 years. It is indicated asfirst-line therapy for patients with metastatic colorectal cancer when treatmentwith a fluoropyrimidine alone is preferred.

"Because Xeloda is a pill, it allows people with colorectalcancer the flexibility of taking their medication on the go without interruptingwork or other activities," said John Marshall, MD, director of thedevelopmental therapeutics program and associate professor of oncology andmedicine of the Lombardi Cancer Center at Georgetown University Medical Center."Also, Xeloda is an effective therapy that has been proven in clinicaltrials to have a superior tumor response rate compared to intravenous bolus5-FU/LV (fluorouracil/leucovorin), also known as the Mayo Regimen."

Clinical Trial Results

The FDA decision was based on the results of two multinationalphase III trials in metastatic colorectal cancer that demonstrate thatcapecitabine was significantly superior to 5-FU/LV (the previous standard ofcare) in its overall tumor response rate. Unlike more complex intravenouschemotherapy regimens, capecitabine requires only two daily oral doses. The drugis covered by Medicare.

The two multinational clinical trials included 1,200 patientsand were conducted at 120 hospitals and cancer centers around the world. Abouthalf the patients enrolled received capecitabine, 1,250 mg/m2 twice daily for 2weeks, followed by 1 week of rest; the other half received IV 5-FU/LV.

In both studies, time to disease progression and survival weresimilar to that achieved with the Mayo Regimen. In one trial, the overallresponse rate was 21% for capecitabine and 11% for the Mayo Regimen; in theother study, the overall response rate was 21% for capecitabine and 14% for IV5-FU/LV. The median time to disease progression was 137 days for capecitabineand 131 days for 5-FU/LV in one study; 128 days for capecitabine and 131 daysfor5-FU/LV in the other study. Median survival was 404 days for capecitabine and369 days for 5-FU/LV in one study; 380 days for capecitabine and 407 days for5-FU/LV in the other study.

Benefits of Oral Therapy

"An oral form of chemotherapy marks a significant advancein colorectal cancer management," said Carolyn Aldigé, president of theCancer Research Foundation of America. "This new chemotherapy forcolorectal cancer gives patients the convenience and benefits of oral dosing,allowing them to spend less time in the hospital and more time with their lovedones, while treating and managing their disease."

Capecitabine is the first oral drug whose effectiveness is dueto its enzymatic activation of 5-FU. The human body produces the enzymethymidine phosphorylase, which converts capecitabine into 5-FU. The drug wasinitially approved in 1998 for use in patients with metastatic breast cancerwhose tumors are resistant to standard chemotherapy with paclitaxel (Taxol) andan anthracycline-containing regimen.