Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous Vasopressin in non-resectable pancreatic cancer
2005 (English)In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 56, no 6, 603-609 p.Article in journal (Refereed) Published
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/m2 and intravenous Leucovorin 100 mg/m2 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 μmol/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.
Place, publisher, year, edition, pages
2005. Vol. 56, no 6, 603-609 p.
intraperitoneal chemotherapy, pancreas cancer, 5-fluorouracil, vasopressin, leucovorin, pharmacokinetics, Adenocarcinoma/*drug therapy/mortality/pathology, Adult, Aged, Aged; 80 and over, Antimetabolites; Antineoplastic/*administration & dosage/pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Area Under Curve, Female, Fluorouracil/*administration & dosage/pharmacokinetics, Hemostatics/*administration & dosage, Humans, Injections; Intraperitoneal, Injections; Intravenous, Leucovorin/administration & dosage, Male, Middle Aged, Palliative Care, Pancreatic Neoplasms/*drug therapy/mortality/pathology, Survival Rate, Vasopressins/*administration & dosage
IdentifiersURN: urn:nbn:se:umu:diva-4273DOI: 10.1007/s00280-005-1012-5PubMedID: 16047145OAI: oai:DiVA.org:umu-4273DiVA: diva2:143291