Cancer Advance: Treatment combinations stall colorectal cancer

Two experimental drugs can buy precious months of remission in some people with colorectal cancer that has spread to other tissues, new research shows. While both drugs are synthetic antibodies, they take distinctly different approaches to fighting the malignancy.

In one trial, scientists show for the first time that patients can benefit from a compound that blocks blood vessel growth, also called angiogenesis, and thus disrupts a tumor’s nutrient supply. In the other trial, a separate substance seems to reawaken a signal within colorectal cancer cells that directs them to commit suicide.

The first drug, bevacizumab, works by inhibiting vascular endothelial growth factor, a protein that directs blood vessel formation in growing tissues, including tumors. The researchers randomly assigned 403 people with untreated colorectal cancer to get bevacizumab, while 412 similar patients received a placebo. Both groups were also given standard chemotherapy.

Tumors shrank by at least half in 45 percent of the patients receiving bevacizumab and 35 percent of those getting the placebo. The group getting the drug averaged nearly 11 months’ of remission while the placebo group averaged 6 months’, reports Herbert I. Hurwitz of the Duke University Medical Center in Durham, N.C. The first group survived, on average, 20.3 months after starting the trial, and those taking the placebo lived only 15.6 months.

Bevacizumab, called Avastin by its maker Genentech in South San Francisco, Calif., failed to stop breast cancer in earlier studies.

In the other trial, researchers enrolled 329 people who had colorectal cancer that had spread despite chemotherapy with the drug irinotecan. The scientists randomly selected one-third to get the drug cetuximab, while the rest got cetuximab plus irinotecan.

The patients’ tumors, which hadn’t responded to irinotecan alone, shrank in 23 percent of those getting both drugs and in 11 percent of those getting just cetuximab. People receiving both treatments went 4 months on average before relapsing, whereas patients getting cetuximab alone experienced remission for only 45 days, reports David Cunningham of the Royal Marsden Hospital in Sutton, England.

Cetuximab, also called Erbitux by its maker ImClone Systems of New York, targets a molecule displayed on cancer cells. The scientists aren’t sure how cetuximab may reactivate chemotherapy, but Cunningham notes that irinotecan often works by igniting a self-destruct reaction in cancerous cells.

The scientists presented their work in Chicago at the 39th annual meeting of the American Society of Clinical Oncology this week. Neither drug has yet been approved in the United States or Europe.

While neither bevacizumab nor cetuximab offers a cure for advanced colorectal cancer, they represent significant progress against the disease, says Mace L. Rothenberg of Vanderbilt University in Nashville. Twenty years ago, the average survival outlook for patients such as those in the trials was 6 months. Now–with these experimental results–survival time can more than triple, he notes. “I can’t think of any other solid-tumor cancer that’s had that magnitude of progress over that time,” he says.


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