The trial, led by David Cunningham, MD, of the Royal Marsden Hospital in England, showed that cetuximab (Erbitux) and irinotecan (Camptosar) given together are more effective than cetuximab alone when treating patients for whom previous treatment has not slowed the disease.
The trial studied colorectal cancer patients whose disease was getting worse despite having been treated with cetuximab. Two-thirds of patients were given the cetuximab and irinotecan combination, and one-third received only cetuximab.
The study results showed:
- The two-drug combination shrank tumors in 22.9% of patients, compared with 10.8% of those who received cetuximab alone.
- Patients who received both cetuximab and irinotecan had no signs of tumor progression for 4.1 months, compared with 1.5 months for patients who received only cetuximab.
- Survival time was 8.6 months for the combination group and 6.9 months for patients who received only cetuximab.
- The one-year survival rates were approximately 30% for both treatment groups.
While researchers suggest that the findings are likely to change the standard of care for patients with metastatic colorectal cancer that has progressed after standard chemotherapy, they also noted that patients who received both cetuximab and irinotecan were more likely to experience severe side effects than those who received only cetuximab.
About 65% of the patients receiving the combination chemotherapy had diarrhea, weakness, low white blood cell count, rash, or vomiting. Nearly half of the patients who took only cetuximab also experienced severe side effects, including difficulty in breathing, weakness, and abdominal pain.
In a related trial studying the side effects of irinotecan, Mark J. Ratain, MD, of the University of Chicago Medical Center, found that some colorectal cancer patients are more likely to experience severe side effects from irinotecan because of a genetic alteration. In the study of 61 patients treated with irinotecan, researchers found that patients who had a particular genetic abnormality were more likely to have low white blood cell countsâa condition that can lead to serious and sometimes life-threatening infectionsâin response to being treated with irinotecan.
In the body, irinotecan is converted into a more powerful form of the drug, called SN-38. Patients with the genetic abnormality lack a well-functioning enzymeâcalled UGT1A1âthat is needed to protect healthy cells from the toxic effects of SN-38. This leads to the patient's increased exposure to SN-38 throughout the entire body, resulting in severe side effects.
"The study's results underscore the need to identify patients genetically predisposed to severe side effects from irinotecan treatment," said Dr. Ratain. "Those patients could be given other chemotherapy drugs or reduced doses of irinotecan."
A predictive genetic test to detect this abnormality is currently available though a clinical trial at the University of Chicago Medical Center. Dr. Ratain estimated that a screening test would become more widely available within the next two years so patients who are predisposed to severe toxicity from irinotecan might be identified by a genetic test before beginning treatment. This could influence both choice of drugs and dosage of drugs, Dr. Ratain said.
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