Drug Helps Fight Late-Stage Colon Cancer in Some Patients

Drug Helps Fight Late-Stage Colon Cancer in Some Patients
WEDNESDAY, Nov. 14 (HealthDay News) -- A highly targeted biologicdrug called cetuximab (Erbitux) is the first to extend the survival ofpatients with advanced colon cancer who have otherwise proved resistant toconventional chemotherapy, Canadian researchers confirmed.
But the drug, which costs $12,000 a month in the United States, appearsto be effective in only about one-third of colon tumors, based on theirspecific gene profile, experts added.
"That's a significant number, but it still leaves a large proportion[of patients] who aren't benefiting," noted lead researcher Dr. DerekJonker, assistant professor of medicine at the University of Ottawa and amedical oncologist at the Ottawa Hospital.
Nevertheless, the success of any new drug is welcome, he added.
"Until now, no anticancer therapy had demonstrated an improvement insurvival in patients for whom chemotherapy was no longer effective, andfor whom supportive care was the only available treatment," Jonker said."So, cetuximab provides new hope for these patients."
The findings were reported in the Nov. 15 issue of the New EnglandJournal of Medicine. The study was funded by the National CancerInstitute of Canada, as well as ImClone Systems and Bristol-Myers Squibb,the two companies that developed the drug.
Colorectal cancer is the third most common kind of cancer and the thirdleading cause of cancer death in the United States. As Jonker explained,most patients are treated with either surgery or conventionalchemotherapy, which typically targets cellular DNA.
Unfortunately, almost all patients with advanced or metastasized coloncancer will develop resistance to standard chemotherapy drugs, hesaid.
"However, now we have a new class of drugs known as the biologicallytargeted therapies, such as cetuximab, and these drugs are targeted todifferent aspects of the tumor biology," Jonker explained. "Many of themare targeted at receptors or signals that trigger a cancer cell togrow."
In the case of cetuximab, the drug's target is the epidermal growthfactor receptor (EGFR), which is found in especially high concentrationson colon cancer cells. Because biologic drugs are finely targeted toaffect cancer cells and not healthy cells, they typically have fewer sideeffects than standard chemotherapy.
In 2004, the U.S. Food and Drug Administration granted cetuximabconditional approval for use in patients with late-stage,chemotherapy-resistant colon cancer. At the time, the agency stated thatfull approval hinged on the outcome of the Canadian trial.
In October, and based on the new findings, the agency followed throughand gave the drug its full approval for this new indication.
In the trial, Jonker's team administered individualized doses ofcetuximab to 287 colon cancer patients treated between late 2003 andAugust 2005. All of the patients had proven resistant to standardchemotherapy. Another 285 patients received supportive/palliative careonly -- the usual option for patients in this situation.
Compared to those who didn't receive the drug, overall survival forpatients receiving cetuximab improved by 23 percent, while survivalwithout any sign of disease progression rose by 32 percent, the researchteam reported.
The incidence of side effects -- including skin rash -- was 78.5percent in the cetuximab group versus about 59 percent for the controlgroup.
One key point, however, was that increases in survival were found onlyamong the 31.4 percent of patients who actually responded to cetuximab,meaning that their cancer stopped growing.
That's probably due to the fact that cetuximab (as well as a relateddrug, panitumumab) only works against a specific subtype of colon cancercell -- those carrying an unmutated version of a particular gene calledKRAS.
"Mutated KRAS almost guarantees no benefit" from cetuximab, said oneexpert, Dr. Axel Grothey, a professor of oncology and chairman of thecolorectal cancer group at the Mayo Clinic, in Rochester, Minn.
For that reason, he said, pre-treatment gene testing may prove crucialto decisions as to whether a particular patient receives cetuximab ornot.
Because it is so expensive -- the costliest drug used today againstcolon cancer -- and because it can induce side effects, "I would likecetuximab to be used in a more individualized way," Grothey said.
He said that most cancer centers, including the Mayo Clinic, do not yethave technologies in place to test tumors for KRAS, but many are lookinginto it.
Jonker agreed that, ideally, KRAS testing and the use of cetuximabwould go hand-in-hand. That way, he said, "We wouldn't have to put[patients] through treatment, and we wouldn't have to suffer the cost oftreatment for people who may not even respond to the drug."
Studies are already under way to see if adding cetuximab to othertherapies will boost survival even further, Jonker said. "The future ofcetuximab is likely to be in combination with chemotherapy or otherbiologically targeted therapies, where the benefits of cetuximab might befurther enhanced," he said.
The drug might also work better if given earlier in the diseaseprocess, before patients have developed resistance to chemotherapy.
In any case, the Canadian trial does give colon cancer patients somenew reason for hope, Grothey said. "We need this drug," he said, "and weprobably need it even earlier."