After a two-year long international clinical trial involving 2000 patients, the FDA approved the first oral chemotherapy drug for the adjuvant treatment of Dukes' C colon cancer. The innovative new drug, Xeloda® (capecitabine) by Roche Pharmaceuticals in New Jersey, was given to half of the patients while the others received intravenous fluorouracil plus leucovorin or 5-FU/LV, the foundation for chemotherapy for the last 40 years. The X-ACT trial, which stands for "Xeloda® in Adjuvant Colon Cancer Therapy" showed that Xeloda® not only met its primary endpoint of non-inferiority to 5-FU/LV but surpassed it by 15 percent according to Dr. Howard A. Burris III, FACP, Director of Drug Development at the Sarah Cannon Research Institute in Nashville, Tenn., one of the lead American accruers in the study.
"You plan a clinical trial with a stated hypothesis — in this case it was that Xeloda® is non-inferior or equivalent to 5-FU/LV — but in actuality there was a 15 percent lower incident of relapse with Xeloda®," Burris says. "Xeloda® was statistically better in some endpoints and clinically better in all endpoints than the IV treatment. There was a decrease of occurances, better overall survival and better tolerances with regard to toxicity compared to the IV. In each and every parameter we used to evaluate the treatment, there was a therapeutic advance."
As one of the lead investigators in the trial that took place in the United States, Europe and Australia, Burris says that the researchers at Sarah Cannon Research Institute participated in the study because there was a need for better therapies for patients who have undergone complete resection of their primary tumor. "The X-ACT trial gave us the opportunity to help the advancement of a drug that provides patients with a more convenient and more effective treatment."
The fact that Xeloda® is in an oral schedule gives patients the flexibility of taking it in the comfort of their own home. The 5-FU/LV, which is administered in 30 office visits over a 24-week period, is much more restrictive compared to only eight visits when Xeloda® is prescribed.
"With Xeloda®, less time is wasted traveling back and fourth to the doctor's office, waiting to receive the IV and even managing the side effects. Patients can spend more time at work and with family," Burris says. "With each parameter that we measured between the oral verses the IV, both in clinical and financial outcomes, the oral drug came out on top." Patients take the pills twice a day, in the morning and night for two weeks on and one week off, then repeat the process for 24-weeks.
"There's been a huge evolution in chemotherapy," states Burris. "We have more potent therapies coming out that are more convenient and better tolerated. In the late '80s and early '90s, the medical community thought we had to increase toxicity in order to kill cancer cells. Now, with drugs like Xeloda®, we're getting greater potency with less toxicity in addition to the convenience of an oral drug. That's a big leap forward for both cancer physicians and patients," notes Burris.
As a matter of fact, physicians and patients alike may already be familiar with the drug. "Xeloda® was initially approved for breast cancer a couple of years ago and it's been utilized in breast and colon cancer," adds Burris. "However, when trying to improve the cure rate for patients who have undergone a resection of their tumor and they're going to be treated with a therapy afterward, physicians like to have confirmatory data. These patients have been put into remission with surgery and now we're trying to eradicate any remaining cancer so we want to use the best tolerated and the most efficacious treatment."
Some of the adverse side effects of using Xeloda® include: diarrhea, nausea, stomatitis, vomiting, fatigue and hand-foot syndrome. In every instance it showed better results than 5-FU/LV, except for Palmar-Plantar Erythrodysesthesia, also known as hand-foot syndrome. This is a side effect of some chemotherapy drugs that results when a small amount of the drug leaks out of the blood vessels and damages tissue.
"About 20 percent of patients will experience some side effects that will require us to adjust the dose or hold the dose for a few days to allow a break," says Burris. "One of the interesting side effects is that there is no hair loss associated with Xeloda® like the IV treatment."
