RTOG 9704 a phase III study of adjuvant pre and post chemoradiation (CRT) 5-FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma
Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 6, 2006
Presenter: William F. Regine Presenter's Affiliation: University of Maryland, Baltimore, MD Type of Session: Scientific
Adenocarcinoma of the pancreas, even when resectable, has a poor prognosis. Failures occur both locoregionally and systemically.
Adjuvant treatment of resected pancreas adenocarcinoma is controversial. Although the ESPAC trial showed that adjuvant chemotherapy alone was superior to chemoradiation, this study has been widely criticized.
Chemoradiation (CRT) with 5FU has been a standard treatment in the U.S.
Gemcitabine (G) is active in pancreas cancer, and confers a survival benefit in the metastatic setting.
RTOG 9704 was designed to determine if the addition of G to postoperative adjuvant 5-FU CRT improved survival for patients with resected pancreatic adenocarcinoma.
Materials and Methods
Phase III Design: Intergroup (RTOG, ECOG, SWOG) trial of randomized to:
Pre and post CRT 5-FU (continuous infusion at 250 mg/m2/day)
Pre and post CRT G (1000 mg/m2 IV weekly)
Patients with pathologic stage T1-4, N0/1, M0 pancreatic adenocarcinoma status post gross total resection. The surgeon on this study reviewed all of the operative notes and pathology reports to confirm gross total resection.
2/3 were node positive
Accrued from 7/1998 - 7/2002
538 pts were entered; 442 were eligible and analyzable
Major reasons for ineligibility
serum not sent for CA-19-9 analysis (n=22)
treatment starting > 8 weeks post surgery (n=19)
Pre CRT treatment was for 3 weeks prior to CRT.
Post CRT treatment was for 12 weeks after CRT.
CRT was 50.4 Gy 1.8 Gy/fx/day with continuous infusion 5-FU, 250 mg/m2/day during radiation
Nodal status (uninvolved vs. involved)
Primary tumor diameter (< 3 cm vs. > 3cm)
Surgical margins (negative vs. positive vs. unknown)
Primary: Overall survival.
original accrual goal was 330 patients, but rapid accrual allowed an amendment to look specifically at overall survival in pancreatic head tumors
Arms were well balanced except for T-stage (T3/4 > for G, p=0.013)
G significantly improved survival in pancreatic head tumors (n=380)
Median survival: 18.8 months G vs. 16.7 months 5-FU
3-yr survival: 31% G vs. 21% 5-FU
HR 0.79 (95% CI 0.63-0.99, p=0.047)
No significant difference when body/tail tumors included (n=442) (p=0.2)
No significant difference in >Grade 3 non-hematologic toxicity
Grade 4 hematologic toxicity rate high in G arm
14% G arm vs. 2% 5-FU arm (p<0.0001)
No difference in febrile neutropenia/infection.
Ability to complete treatment per study was similar:
chemo (86%, 5-FU vs. 90%, G) and RT (85%, 5-FU vs. 88%, G)
The addition of G to postoperative adjuvant 5-FU CRT significantly improves survival in pts with pancreatic head adenocarcinoma.
Although the optimum adjuvant treatment for resected adenocarcinoma remains controversial, this study explored the best adjuvant chemotherapy to be combined with 5-FU sensitized CRT
This study was designed to evaluate adenocarcinoma of the pancreatic head as a primary endpoint. In this population there was a clear advantage to G of 5-FU for pre- and post-chemotherapy that sandwiched the CRT
The RTOG will adopt Gemzar followed by 5-FU/XRT followed by additional Gemzar as the standard for future clinical trials of adjuvant pancreatic cancer
Jul 18, 2012 - For most patients with locally advanced pancreatic carcinoma (LAPC), induction with a combination of gemcitabine and oxaliplatin (GEMOX) followed by chemoradiotherapy (CRT) is feasible, resulting in clinical benefit, a chance of resectability, and improved survival, according to a study published online July 6 in Cancer.