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/ m(2) once weekly for 3 consecutive weeks, and oral UFT 390 mg/ m(2)/ 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. Copyright (C) 2004 S. Karger AG, Basel.