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Treatment of non-resectable pancreatic cancer with intraperitoneal 5-FU and leucovorin IV
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
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2001 In: European Journal of Surgical Oncology, Vol. 27, no 5, 477-481 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2001. Vol. 27, no 5, 477-481 p.
URN: urn:nbn:se:umu:diva-4270OAI: diva2:143288
Available from: 2004-11-18 Created: 2004-11-18Bibliographically approved
In thesis
1. Intraperitoneal 5-Fluorouracil treatment of cancer - clinical and experimental studies
Open this publication in new window or tab >>Intraperitoneal 5-Fluorouracil treatment of cancer - clinical and experimental studies
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background:Pancreas cancer is a most aggressive malignancy. More than 80% of patients diagnosed with pancreas cancer, exhibit such advanced disease, that curative surgery is impossible. Systemic chemotherapy prolongs survival to 5-9 months. High concentrations of chemotherapeutic agents in the abdominal cavity and in the lymphatics draining the area is achieved by intraperitoneal administration. Vasopressin decreases splanchnic blood flow, reducing the intraperitoneal uptake of drugs, thus raising the local and lymphatic dose intensity.

Aim: The aim of the study was to investigate the feasibility and tumour response of intraperitoneal 5-Fluorouracil (5-FU) treatment in non-resectable pancreas cancer, using vasopressin to improve the pharmacokinetic profile. Further, to study the effect of vasopressin on peritoneal blood flow, altered by intraperitoneal 5-FU or the presence of peritoneal carcinomatosis.

Methods: In the animal experiments, the 133Xe-clearance technique and as a comparison Laser doppler flow, were used to identify changes of peritoneal blood flow caused by vasopressin in unmanipulated animals and in animals with peritoneal carcinomatosis or animals given intraperitoneal 5-FU. In the clinical studies, 68 (39 women/29 men) patients, with a non-resectable ductal pancreas cancer and a Karnovsky Index ≥70 were included. Patients were treated with 750-1500 mg/m2 5-FU intraperitoneally through a Port-a-cath and Leucovorin 100 mg/m2 intravenously on two consecutive days every 21 days until progression. Seventeen patients, receiving 750 mg/m2 5-FU, were given concomitant vasopressin 0.1 IU/min during 180 minutes, alternatively day 1 or 2.

Results: In the animal experiments, vasopressin 0.07 IU/kg/min significantly reduced the 133Xe-clearance. Intraperitoneal 5-FU decreased the basal peritoneal blood flow and abrogated the vasopressin effect for 1-2 days. The presence of peritoneal carcinomatosis did not influence the basal peritoneal blood flow, nor the reduction of peritoneal blood flow caused by vasopressin. In the clinical studies, the treatment with intraperitoneal 5-FU was well tolerated, with no WHO Grade 3 or 4 toxicity with doses up to 1250 mg/m2. Thirty patients achieved at least stable disease at three months. The median survival time was 8.0 (range 0.8-54.1) months. There was a significant reduction of 5-FU Cmax on day 2, but no significant reduction of AUC, when vasopressin was given.

Conclusion: Peritoneal blood flow changes caused by vasopressin can be estimated with the 133Xe-clearance technique. Intraperitoneal 5-FU but not peritoneal carcinomatosis decreases the vasopressin induced 133Xe-clearance reduction, 1-2 days after administration. In patients with non-resectable pancreas cancer, intraperitoneal 5-FU up to 1250 mg/m2 for two days every third week can be given without WHO grade 3 and 4 toxicity. The treatment is well tolerated with few and minor side effects. Tumour responses were observed. Addition of vasopressin does not significantly enhance the pharmacokinetics of intraperitoneal 5-Flurorouracil, but adds toxicity.

Place, publisher, year, edition, pages
Umeå: Kirurgisk och perioperativ vetenskap, 2004. 98 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 935
Surgery, intraperitoneal, 5-fluorouracil, pancreas cancer, vasopressin, Xenon-clearance, Kirurgi
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Research subject
urn:nbn:se:umu:diva-372 (URN)91-7305-747-9 (ISBN)
Public defence
Available from: 2004-11-18 Created: 2004-11-18Bibliographically approved

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