ACCORD 12/0405 Prodige 2: Radiation dose intensification with capecitabine/oxaliplatin may be optimal for rectal adenocarcinoma

Issue: December 10, 2009

Radiation dose intensification combined with capecitabine and oxaliplatin did not increase surgical complications and may provide a trend toward an increase in negative circumferential positive rectal margin and pathologic complete response, according to the findings of a phase-3 trial.

Jean-Pierre Gerard, MD, professor at the University of Oncology-Radiotherapy at Centre Antoine-Lacassagne, in Nice, France, presented findings from the ACCORD 12/0405 Prodige 2 trial. Previous randomized trials have shown that better local control of rectal adenocarcinoma can be achieved using neoadjuvant chemoradiation. This trial was conducted to determine an optimal regimen.

Between November 2005 and July 2008, 586 patients were assigned to concurrent radiotherapy 45 Gy/25 fractions for five weeks plus capecitabine 800 mg/m² twice a day (arm A) or to concurrent radiotherapy 50 Gy/25 fractions for five weeks plus capecitabine 800 mg/m² twice a day plus oxaliplatin 50 mg/m² per week (arm B).

Grade-3 and grade-4 toxicity was 11% in arm A vs. 25% in arm B (P=.01). In the group assigned 45 Gy (arm A), 98% of patients had surgery; in the group assigned 50 Gy (arm B), 98.6% of patients had surgery.

No difference was observed between groups for sphincter-saving surgery. Postoperative death at 60 days was the same in both groups. A circumferential positive rectal margin (0 mm to 1 mm) was found in 11% of patients in arm A vs. 6% of patients in arm B (P=.12). For circumferential positive rectal margin (0 mm to 2 mm), the rate was 18% in arm A and 8% in arm B (

P <.05). The pathologic complete response was 13.8% for arm A and 18.8% for arm B (P=.11).

A dose of 50 Gy in five weeks may be proposed in locally advanced rectal cancer as an efficient schedule, according to researchers.

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Gerard JP. #11.