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Reuters Health Information (2008-03-20): Perioperative chemotherapy lowers recurrence of hepatic metastases


Perioperative chemotherapy lowers recurrence of hepatic metastases

Last Updated: 2008-03-20 18:30:01 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Oxaliplatin-based chemotherapy administered before and after resection of liver tumors secondary to colorectal cancer improves progression-free survival compared with tumor resection alone, according to the results of a multinational trial.

Surgical resection is considered the standard of care for patients with hepatic metastases, Dr. Bernard Nordlinger of the Centre Hospitalier Universitaire Ambroise Pare, Boulogne-Billancourt, France, and colleagues note in the March 22nd issue of The Lancet. Although relapse is common in these patients, there is no clear evidence that combined treatment with perioperative chemotherapy is any more effective than surgery alone.

The EORTC Intergroup trial 40983 included 364 patients with colorectal cancer and up to four resectable liver metastases. Patients were randomly assigned to surgery alone or to surgery plus FOLFOX4 chemotherapy, six cycles before and six cycles after surgery.

Eleven patients in each group were deemed ineligible following randomization, primarily because of advanced disease. A total of 152 patients in the surgery-only group and 151 in the adjuvant-chemotherapy group underwent tumor resection.

In the intention-to-treat analysis, 3-year progression-free survival did not differ significantly between groups.

However, among patients who underwent resection, the absolute increase in the rate of progression-free survival at 3 years was 9.2% (33.2% in the surgery-only group vs 42.4% in the adjuvant chemotherapy group, hazard ratio 0.73, p = .025).

Dr. Nordlinger and his associates note that metastasis progression occurred during preoperative chemotherapy in 12 patients, 4 of whom were able to undergo resection. "Progression during preoperative chemotherapy should be regarded as a biological marker for poor prognosis and an indication for administration of second-line chemotherapy before surgery is considered," they advise.

They conclude: "Perioperative FOLFOX4 chemotherapy reduced the risk of events of progression-free survival by a quarter and was compatible with major surgery."

However, authors of an accompanying commentary point out that the degree of improvement in the combined-treatment group was "remarkably similar to the benefit seen previously with FOLFOX in patients with unresectable metastatic disease."

Dr. Scott Kopetz and Dr. Jean-Nicolas Vauthey from the University of Texas MD Anderson Cancer Center in Houston argue that "FOLFOX delays progression of disease but does not improve long-term survival compared with surgery alone." The primary advantage to FOLFOX, they suggest, is to identify patients most likely to benefit from hepatic resection.

Lancet 2008;371:963-965,1007-1016.

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