Gemcitabine Plus Chemoradiation of Small Benefit for Resected Pancreatic Cancer

NEW YORK MAR 04, 2008 (Reuters Health) - The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation for patients with resected pancreatic adenocarcinoma provides a small survival benefit, but it is generally not statistically significant, according to a report in the Journal of the American Medical Association for March 5.

The Radiation Therapy Oncology Group 97-04 phase III trial included 451 patients who had undergone complete gross total resection of pancreatic adenocarcinoma. Tumors were localized to the pancreatic head in 388 patients.

Lead author Dr. William F. Regine, from the University of Maryland in Baltimore, and his associates note that 34% of patients had microscopically positive margins following resection, and 25% had pathology reports with unknown surgical margin status.

Subjects were randomized to fluorouracil (continuous infusion of 250 mg/m² per day) or to a 30-minute infusion of 1000 mg/m² of gemcitabine once weekly. The two trial treatments were administered for 3 weeks prior to chemoradiation (50.4 Gy in 28 fractions, 5 days/week, with infusion of fluorouracil) and again for 3 months afterward.

In the group as a whole and among those with pancreatic head tumors, overall survival was not significantly affected by treatment allocation.

Specifically, among patients with pancreatic head tumors, median survival was 20.5 months in the gemcitabine group and 16.9 months in the fluorouracil group (p = 0.09).

However, after adjusting for nodal status, tumor diameter, and surgical margin status for patients with pancreatic head tumors, the treatment effect yielded a hazard ratio of 0.80 (p = 0.05) toward improved survival for the gemcitabine group, Dr. Regine"s group reports.

Other than asymptomatic hematologic toxicity, patients receiving gemcitabine were no more prone to adverse effects than those receiving fluorouracil, the report indicates.

In an accompanying editorial, Dr. James L. Abbruzzese criticizes the RTOG 97-04 study, noting that "these investigators have not developed pathological quality control to the point at which clinicians can be confident that a microscopically positive margin can be accurately differentiated from a grossly incomplete resection."

Surgical outcomes can be improved, says the editorialist from the University of Texas MD Anderson Cancer Center in Houston, by incorporation of sophisticated diagnostic studies and multidisciplinary management at high-volume centers.

"Finally, and most importantly," he adds, "efforts must be redoubled to develop a new generation of promising therapeutics, and the commitment must be increased to understand and test them in prospectively defined patient subsets -- not the means to detect marginal or incremental improvements in clinical trials of large numbers of unselected patients."

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