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A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer

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Abstract

Purpose

The purpose of this phase I study was to determine the safety, toxicity, maximum tolerated dose, and pharmacokinetics of capecitabine when administered concurrently with radiotherapy in patients with localised, inoperable pancreatic adenocarcinoma.

Methods

Eligible patients, with adequate performance status and organ function, were treated in escalating dose cohorts with capecitabine, administered 7 days a week, twice daily, and radiotherapy (50.4 Gy in 28 fractions over 38 days). Cohorts of six patients were treated at four planned dose levels. Pharmacokinetic (PK) studies were undertaken on day 1 of treatment.

Results

Twenty-five patients, performance status ECOG ≤2, were recruited to the study. Dose-limiting toxicities were grade 3 vomiting (1 patient) and grade 3 fatigue (1 patient), both at 1,000 mg/m2. The recommended phase II dose was 825 mg/m2. No grade 3/4 haematological toxicities were observed. PK studies did not suggest any effect of pancreatic malignancy or concurrent radiotherapy on the PK parameters of capecitabine and its metabolites.

Conclusion

Capecitabine-based chemo-radiotherapy, using a twice daily dosing schedule of 825 mg/m2 given 7 days per week concurrently with 50.4 Gy external beam radiotherapy, is well tolerated in patients with locally advanced pancreatic cancer.

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Acknowledgments

This study was supported by Cancer Research UK Glasgow Clinical Trials Unit (funded by Cancer Research UK), the Glasgow Experimental Cancer Medicine Centre (ECMC: Cancer Research UK and Chief Scientist Office, Scotland) and by Roche Products UK. The authors are grateful to the study teams at the participating centres for support of this study.

Conflict of interest

All authors completed a disclosure form. The following author indicated the following potential conflict of interest. Professor T R Jeffry Evans: Consultant/advisory role for Roche. Research funding from Roche.

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Authors and Affiliations

  1. Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow, G12 OYN, UK

    Patricia Roxburgh, Graeme R. Lumsden, Allan James, Rosemary Morrison, T. R. Jeffry Evans & Alexander C. McDonald

  2. Institute of Cancer Sciences, Cancer Research UK Beatson Institute, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK

    Patricia Roxburgh & T. R. Jeffry Evans

  3. Cancer Research UK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow, G12 OYN, UK

    James Paul & Lorna Sweeting

  4. Epidemiology and Statistics Core, Wellcome Trust Clinical Research Facility, University of Edinburgh, Edinburgh, UK

    Sharon Harden

  5. St. James’s Institute of Oncology, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK

    Adrian Crellin

Authors
  1. Patricia Roxburgh
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  2. Graeme R. Lumsden
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  3. James Paul
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  4. Sharon Harden
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  6. Allan James
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  7. Adrian Crellin
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  8. Rosemary Morrison
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  9. T. R. Jeffry Evans
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  10. Alexander C. McDonald
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Corresponding author

Correspondence to Alexander C. McDonald.

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Roxburgh, P., Lumsden, G.R., Paul, J. et al. A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer. Cancer Chemother Pharmacol 74, 131–139 (2014). https://doi.org/10.1007/s00280-014-2470-4

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  • DOI: https://doi.org/10.1007/s00280-014-2470-4

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