The US Food and Drug Administration (FDA) has approved
capecitabine (Xeloda), the first oral chemotherapy for the treatment of
metastatic colorectal cancer (the second leading cause of cancer mortality among
Americans). Capectibine is only the second treatment for colorectal cancer
approved in the United States in the past 40 years. It is indicated as
first-line therapy for patients with metastatic colorectal cancer when treatment
with a fluoropyrimidine alone is preferred.
"Because Xeloda is a pill, it allows people with colorectal
cancer the flexibility of taking their medication on the go without interrupting
work or other activities," said John Marshall, MD, director of the
developmental therapeutics program and associate professor of oncology and
medicine of the Lombardi Cancer Center at Georgetown University Medical Center.
"Also, Xeloda is an effective therapy that has been proven in clinical
trials to have a superior tumor response rate compared to intravenous bolus
5-FU/LV (fluorouracil/leucovorin), also known as the Mayo Regimen."
Clinical Trial Results
The FDA decision was based on the results of two multinational
phase III trials in metastatic colorectal cancer that demonstrate that
capecitabine was significantly superior to 5-FU/LV (the previous standard of
care) in its overall tumor response rate. Unlike more complex intravenous
chemotherapy regimens, capecitabine requires only two daily oral doses. The drug
is covered by Medicare.
The two multinational clinical trials included 1,200 patients
and were conducted at 120 hospitals and cancer centers around the world. About
half the patients enrolled received capecitabine, 1,250 mg/m2 twice daily for 2
weeks, followed by 1 week of rest; the other half received IV 5-FU/LV.
In both studies, time to disease progression and survival were
similar to that achieved with the Mayo Regimen. In one trial, the overall
response rate was 21% for capecitabine and 11% for the Mayo Regimen; in the
other study, the overall response rate was 21% for capecitabine and 14% for IV
5-FU/LV. The median time to disease progression was 137 days for capecitabine
and 131 days for 5-FU/LV in one study; 128 days for capecitabine and 131 days
5-FU/LV in the other study. Median survival was 404 days for capecitabine and
369 days for 5-FU/LV in one study; 380 days for capecitabine and 407 days for
5-FU/LV in the other study.
Benefits of Oral Therapy
"An oral form of chemotherapy marks a significant advance
in colorectal cancer management," said Carolyn Aldigé, president of the
Cancer Research Foundation of America. "This new chemotherapy for
colorectal cancer gives patients the convenience and benefits of oral dosing,
allowing them to spend less time in the hospital and more time with their loved
ones, while treating and managing their disease."
Capecitabine is the first oral drug whose effectiveness is due
to its enzymatic activation of 5-FU. The human body produces the enzyme
thymidine phosphorylase, which converts capecitabine into 5-FU. The drug was
initially approved in 1998 for use in patients with metastatic breast cancer
whose tumors are resistant to standard chemotherapy with paclitaxel (Taxol) and
an anthracycline-containing regimen.