The median OS for the 388 patients with pancreatic head tumors was 20.5 months in the gemcitabine arm versus 16.9 months in the 5-FU arm; 3-year survival was 31% versus 22%, respectively (P = .09; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.65–1.03). OS for all patients was not reported in the publication; however, median survival estimates extrapolated from the presented survival curve were approximately 19 months for the gemcitabine group and 17 months for the 5-FU group.[Level of evidence: 1iiA]
Results have also been reported from CONKO-001, a multicenter, phase III trial of 368 patients with resected pancreatic cancer who were randomly assigned to six cycles of adjuvant gemcitabine versus observation. In contrast to the previous trials, the primary endpoint was disease-free survival (DFS). Median DFS was 13.4 months in the gemcitabine arm (95% CI, 11.4–15.3) and 6.9 months in the observation group (95% CI, 6.1–7.8; P < .001). However, there was no significant difference in OS between the gemcitabine arm (median 22.1 months, 95% CI, 18.4–25.8) and the control group (median 20.2 months, 95% CI, 17–23.4).[Level of evidence: 1iiDii] At the American Society of Clinical Oncology annual meeting in 2008, the investigators, with longer follow-up, reported a significant improvement in OS that favored gemcitabine (median survival 22.8 months vs. 20.2 months, P = .005; 5-year survival 21% vs. 9%).
The ESPAC-3 (NCT00058201) trial randomly assigned 1,088 patients who had undergone complete macroscopic resection to either 6 months of 5-FU (425 mg/m2) and folinic acid (20 mg/m2) on days 1 to 5 every 28 days or 6 months of gemcitabine (1,000 mg/m2) on days 1, 8, and 15 every 28 days. Median OS was 23.0 months (95% CI, 21.1– 25.0) for patients treated with 5-FU plus folinic acid and 23.6 months (95% CI, 21.4–26.4) for those treated with gemcitabine (HR, 0.94, 95% CI, 0.81–1.08, P = .39).[Level of evidence: 1iiA]
Additional trials are still warranted to determine more effective adjuvant therapy for this disease.
Standard treatment options:
- Radical pancreatic resection:
- Whipple procedure (pancreaticoduodenal resection).
- Total pancreatectomy when necessary for adequate margins.
- Distal pancreatectomy for tumors of the body and tail of the pancreas.[19,20]
- Radical pancreatic resection with postoperative chemotherapy (gemcitabine or 5-FU/folinic acid).
- Radical pancreatic resection with postoperative 5-FU chemotherapy and radiation therapy.[9,10,11,12,13]
Treatment options under clinical evaluation:
- Gemcitabine and capecitabine (ESPAC-4).
- Gemcitabine and erlotinib (CONKO-005).
- Gemcitabine and erlotinib with or without 5-FU/capecitabine-based chemoradiation (RTOG-0848).
- Preoperative chemotherapy and/or radiation therapy.