Microsatellite-instability status predicts benefit of adjuvant chemotherapy for colon cancer

Fluorouracil-based adjuvant chemotherapy offers no benefits and may be harmful to colon cancer patients whose tumors have high levels of microsatellite instability, according to a report published in the July 17th issue of The New England Journal of Medicine.

If confirmed in further studies, “our findings would indicate that microsatellite-instability testing should be conducted routinely and the results used to direct rational adjuvant chemotherapy in colon cancer,” senior author Dr. Steven Gallinger, from Mount Sinai Hospital in Toronto, and colleagues note.In the new study, 570 tumor specimens from patients with stage II or III colon cancer were analyzed for microsatellite instability. All of the patients underwent curative resection of their tumor, including 283 who received fluorouracil-based adjuvant chemotherapy.During a median follow-up period of 7.4 years, 185 of the patients died, the investigators report.Among patients who did not receive chemotherapy, high-frequency microsatellite instability was associated with improved 5-year survival compared with those with no instability or low-frequency instability (p = 0.004).However, in patients who received chemotherapy, high-frequency microsatellite instability was not tied to improved survival. In fact, there was evidence that giving fluorouracil-based chemotherapy to patients with this tumor status actually decreased their survival. “The finding that fluorouracil-based adjuvant chemotherapy does not significantly increase, and may potentially decrease, overall and disease-free survival among patients with tumors exhibiting high-frequency microsatellite instability raises several provocative issues regarding postoperative management of stage II and stage III colon cancer,” the authors note.”However, we would urge caution and not advocate altering clinical decision making on the basis of our findings,” they add. (Source: N Engl J Med 2003;349:247-257: Reuters Health: July 16, 2003: Oncolink)