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

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Abstract

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.

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Abbreviations

5-FU:

5-Fluorouracil

IP:

intraperitoneal

PAC:

Port-a-cath

AUC:

area under the curve

Cmax:

peak plasma concentration

VP:

vasopressin

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Acknowledgements

Grant Support: This investigation was supported by grants from Swedish Cancer Society 4144-B99-02XBC, 0512-B99-12XCC, and 4600-B03-03XAC, and the Cancer Research Foundation in Umeå, AMP 97-132 and AMP 99-224

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Authors and Affiliations

  1. Department of surgical and perioperative science; Surgery, Umeå University Hospital, 90185, Umeå, SE, Sweden

    M. Öman & P. Naredi

  2. Department of radiology, Umeå University Hospital, 90185, Umeå, SE, Sweden

    S. Lundqvist

  3. Department of surgery, Sahlgrenska University Hospital, 413 45, Göteborg, SE, Sweden

    B. Gustavsson & LO. Hafström

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  1. M. Öman
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  2. S. Lundqvist
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  3. B. Gustavsson
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  4. LO. Hafström
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  5. P. Naredi
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Correspondence to M. Öman.

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Öman, M., Lundqvist, S., Gustavsson, B. et al. Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous Vasopressin in non-resectable pancreas cancer. Cancer Chemother Pharmacol 56, 603–609 (2005). https://doi.org/10.1007/s00280-005-1012-5

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  • DOI: https://doi.org/10.1007/s00280-005-1012-5

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