RTOG 9704 a phase III study of adjuvant pre and post chemoradiation (CRT) 5-FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma

4007 Background: RTOG 9704 was designed to determine if the addition of G to postoperative adjuvant 5-FU CRT improved survival for patients(pts) with resected pancreatic adenocarcinoma. Methods: In this Intergroup trial involving RTOG, ECOG and SWOG, pts post gross total resection of pancreatic adenocarcinoma (path stage T1 - 4, N0 - 1, M0) were randomized to receive pre and post CRT 5-FU vs pre and post CRT G. 5-FU = continuous (CI) at 250 mg/m 2 /day. G = 1000 mg/m 2 IV weekly. Both were given over 3 weeks pre and 12 weeks post - CRT. CRT = 50.4 Gy 1.8 Gy/fx/day with CI 5-FU, 250 mg/m 2 /day during RT for all pts. Pts were stratified by nodal status (uninvolved vs involved), primary tumor diameter ( < 3 cm vs ≥ 3 cm) and surgical margins (negative vs positive vs unknown). Survival was the primary endpoint with an original targeted accrual of 330 pts. Rapid enrollment allowed study amendment for increased targeted accrual to add survival among pts with lesions of the pancreatic head as a primary, prospective endpoint. Results: From 7/98 - 7/02, 538 pts were entered; 442 were eligible and analyzable. Major reasons for patient ineligibility were serum not sent for CA-19–9 analysis (n=22) and treatment starting > 8 weeks post surgery (n=19). Treatment arms were well balanced except for T-stage (T3/4 > for G, p=0.013). Pts with pancreatic head tumors(n=380) experienced significantly improved survival, with median and 3-year survival of 18.8 months and 31% respectively for the G arm vs. 16.7 months and 21% for the 5-FU arm (p=0.047; HR=0.79, CI=0.63–0.99). When analysis was inclusive of pts with body/tail tumors(n=442) no significant difference in survival was found (p=0.20). No significant difference in non-hematologic grade ≥ 3 toxicity was seen. The grade 4 hematologic toxicity rate was 14% in the G arm and 2% in the 5-FU arm (p<0.0001) without difference in febrile neutropenia/infection. The ability to complete chemotherapy (86%, 5-FU vs. 90%, G) and RT (85%, 5-FU vs. 88%, G) as per study was similar. Conclusions: The addition of G to postoperative adjuvant 5-FU CRT significantly improves survival in pts with pancreatic head adenocarcinoma. No significant financial relationships to disclose.