Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous Vasopressin in non-resectable pancreas cancer

Background: Systemic palliative treatment with chemotherapy against advanced pancreas cancer has low effectiveness despite considerable toxicity. Aim: To investigate the safety, toxicity and tumour response of intraperitoneal 5-Fluorouracil (5-FU) with intravenous Leucovorin and to monitor 5-FU pharmacokinetics in plasma during intraperitoneal instillation with and without vasopressin in patients with non-resectable pancreas cancer. Patients/methods: Between 1994 and 2003, 68 patients with non-resectable pancreas cancer TNM stage III and IV, were enrolled to receive intraperitoneal 5-FU instillation 750-1500 mg/m(2) and intravenous Leucovorin 100 mg/m(2) for two days every third week. Tumour response, performance status and toxicity were recorded. Seventeen patients were also treated with intravenous vasopressin 0.1 IU/minute for 180 minutes, during intraperitoneal 5-FU instillation. Area under the curve (AUC) and peak concentration (Cmax) of 5-FU in plasma were analysed. Results: The treatment was well tolerated with minor toxicity. One complete response (54.1+ months) and 2 partial responses were observed. Time to progression was 4.4 months (0.8-54.1+), and median survival was 8.0 months (0.8-54.1+). There was a significant reduction of 5-FU Cmax in plasma the second day of treatment if vasopressin was used (3.4 +/- 2.5 and 6.1 +/- 5.4 mu mol/l, respectively, p < 0.05). 5-FU AUC in plasma was not significantly affected by vasopressin either day of treatment. Conclusion: Intraperitoneal 5-FU is a safe treatment with low toxicity to patients with non-resectable pancreas cancer. Tumour response was 4.4% and median survival time 8.0 months. Addition of vasopressin did not significantly decrease plasma 5-FU AUC but reduced Cmax on day 2 of treatment.