Phase II Study of Gemcitabine Combined with Uracil-Tegafur in Metastatic Pancreatic Cancer

Objective: The single agent gemcitabine is the standard first-line treatment for advanced pancreatic cancer. Recent studies of a combination of gemcitabine and 5-fluorouracil (5-FU) revealed that survival data were superior to those with gemcitabine or 5-FU alone. The administration of oral uracil-tegafur (UFT) is more convenient and simulates the effect of a continuous or protracted infusion of 5-FU. Therefore, we conducted a phase II study of gemcitabine combined with UFT in metastatic pancreatic cancer patients and assessed the efficacy and the toxicity of the regimen. Methods: Twenty-two pancreatic adenocarcinoma patients (18 males, 4 females) were enrolled from December 2000 to September 2002. The regimen consisted of gemcitabine 1,000 mg/m2 once weekly for 3 consecutive weeks, and oral UFT 390 mg/m2/day (in 3 divided doses) on days 1–14. The cycle was repeated every 28 days. The objective tumor response was evaluated after 2 courses of chemotherapy. Results: 82 cycles were administered in total, with a median of 3 cycles per patient (range 1–6 cycles). The median age was 52 years (range 28–69 years). Response to treatment could be assessed in all patients. The objective response rate was 22.7% (95% CI, 7.8–45.4) with no complete response and 5 partial responses. Four patients (18.2%) had stable disease and 13 patients (59.1%) had a progression. The median time to progression was 4.2 months (range 0.9–13.6). The median overall survival was 5.8 months (range 0.5–13.6). Of 10 patients eligible for the assessment of clinical benefit response, 4 (40%, 95% CI 12.2–73.8) showed clinical benefit. Among 21 patients with baseline CA 19-9 levels, CA 19-9 was reduced by 50% or more in 12 patients (57.1%). The chemotherapy was generally well tolerated and the most common grade 3–4 toxic side effects were neutropenia (18.2%), anemia (4.5%), and diarrhea (4.5%). Conclusion: The combination chemotherapy with gemcitabine and UFT in metastatic pancreatic cancer was tolerable for most patients but showed modest response rates and clinical benefit. However, a randomized phase III study should be conducted in order to further test the efficacy of the regimen.