Phase II study on low dose gemcitabine plus oral chemotherapy with uracil-tegafur and cyclophosphamide in combination with radiotherapy against recurrent and advanced pancreatic cancer.

The present study assessed the anti-tumor effects and clinical benefits of intravenous (i.v.) or intra-arterial (i.a.) gemcitabine (GEM) at low dose plus oral chemotherapy with uracil-tegafur (UFT) and cyclophosphamide (CPA) in combination with radiotherapy (RT) against recurrent and advanced pancreatic cancers. A total of 22 patients with 15 advanced or 7 recurrent pancreatic cancer were enrolled. The target lesions included 15 primary tumors, 9 liver metastases, 3 local recurrences, 1 lung metastasis and 1 pleural effusion. The patients were each given GEM at 200-400 mg weekly or biweekly, UFT at 300 mg/day daily and CPA at 50 mg/day every other day in combination with RT at a total dose of 40-60 Gy. The primary efficacy measures were the overall response rate (RR) and survival. Furthermore, the clinical benefit response (CBR) was classified by measuring the pain intensity, analgesic consumption, Karnofsky performance status and body weight. The regimen was well tolerated, and the major side effects included anorexia, general malaise and myelo-suppression. In each case, dose reduction was effective in resolving these side effects. The dose limiting side effect was thrombocytopenia. Eleven patients received i.v. GEM alone, 6 patients received i.a. GEM alone and 5 patients received both. The objective responses were evaluated in all patients, and the overall RR was 27% (2 complete responses, 4 partial responses, 6 stable diseases and 10 progressive diseases). A CBR was experienced in 22.7% of the patients. The mean survival period was 10.6 months (2-20 months), and the 1-year survival rate was 42.2%. There were no differences in RR and survival among the different administration methods of GEM. In conclusion, i.v. or i.a. GEM at low dose, UFT and CPA in combination with RT is a well-tolerated regimen with beneficial clinical efficacy, and is worthy of further study.