A new study published in the Journal of Clinical Oncology (Vol. 22, No. 1: 23-30) suggests the recently approved drug oxaliplatin can improve survival and should become standard first-line treatment for patients with advanced colorectal cancer. Experts say the research illustrates just how quickly new drugs – and new ways of administering older drugs – are revolutionizing the treatment of this deadly disease.

"Today, fewer stage III colorectal cancer patients relapse and more and more stage IV patients are alive at 2 or 3 years… likely as a result of using these new regimens," said Alberto Sobrero, of the Osepedale San Martino in Genoa, Italy, who wrote an editorial accompanying the study.

Colorectal cancer is the second leading cause of cancer related deaths in the United States. The American Cancer Society estimates that 147,000 Americans will be diagnosed with colorectal cancer in 2004, and 56,730 people will die from it.

Early detection of this disease can prevent many of these deaths, but screening rates are low and many people aren't diagnosed until the cancer is advanced and liable to spread throughout the body. People with advanced disease are less likely to survive than people whose colon cancer is found at an early stage.

For years the standard treatment to try to prevent this spread, and also to treat the cancer if it had already spread, was chemotherapy with 2 drugs, 5-Fluorouracil (5-FU) and leucovorin. Usually the drugs were given together as an intravenous injection over a few minutes. Although this regimen helped some patients, many did not benefit.

Things began to change in the late 1990s when French doctors led by Aimery de Gramont, MD, devised a more effective and less toxic way of giving these drugs. Instead of giving the drugs all at once, they gave the 5-FU by continuous intravenous infusion over 2 days every 2 weeks along with injections of the leucovorin. More than twice as many patients on that regimen experienced major tumor shrinkage with fewer side effects (Journal of Clinical Oncology Vol. 15, No. 2: 808-817). This treatment regimen is now commonly called the de Gramont regimen.

At the same time, a new drug called irinotecan, given alone, was helping patients with widespread colorectal cancer who were no longer responding to 5-FU and leucovorin. The drug was even more effective when given along with 5-FU and leucovorin. Researchers led by Leonard Saltz, MD, found that patients given all 3 drugs were more likely to have tumor shrinkage and live more than 2 months longer than patients who only received 5FU and leucovorin (New England Journal of Medicine Vol. 343, No. 13: 905-914). This treatment is now known as the Saltz regimen.

Oxaliplatin, which was approved by the US Food and Drug Administration in August, 2002, has shown even more promise when given along with 5-FU and leucovorin. Results presented at an oncology meeting last year suggested that this drug combination could better prevent cancer recurrence in people with large tumors or tumors that had spread to the lymph nodes.

In the new study, doctors at the University of North Carolina, Chapel Hill, and other institutions, found that patients who received this drug combination lived longer than patients receiving 5-FU/leucovorin combinations containing irinotecan.

The study enrolled 795 patients who had widespread colorectal cancer. They were divided into 3 groups. One group received oxaliplatin and 5-FU and leucovorin, with the 5-FU given by infusion over 2 days. A second group received irinotecan and 5-FU and leucovorin. This time, the 5-FU and leucovorin were given by injection over a few minutes. The third group was given irinotecan and oxaliplatin together, with no 5-FU or leucovorin.

The oxaliplatin, 5-FU/leucovorin combination held the tumor in check the longest and appeared to help patients live longer. It also caused the fewest side effects. The only major problem for patients on this treatment was numbness and tingling that eventually went away in most cases. The other regimens were far more toxic, causing more nausea and vomiting and also severe diarrhea.

Because the oxaliplatin treatment is more effective and less toxic, the study authors conclude that it should become standard therapy. Editorialist Sobrero agreed, but noted that because there has been such a substantial improvement in treating colorectal cancer recently, other drug combinations now being tested may prove just as useful.

The drug bevacizumab (Avastin), for instance, appears to help patients with advanced colorectal cancer respond better to treatment and live longer, when it is given in combination with 5-FU and leucovorin. Avastin is an anti-angiogenesis drug. It prevents blood vessel growth and is thought to kill tumors by preventing them from being nourished. Avastin is on a fast track at the FDA and may receive approval this year.

Another new therapy now in trials is capecitabine, a form of 5-FU administered as a pill. Replacing the cumbersome 5-FU infusion with a pill would be a great benefit to patients if it also proved to be effective.