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A randomised controlled trial of ALA vs. Photofrin photodynamic therapy for high-grade dysplasia arising in Barrett’s oesophagus

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Abstract

Photofrin photodynamic therapy (PDT) is a licenced treatment for Barrett’s oesophagus (BE) with high-grade dysplasia (HGD) but causes strictures and photosensitivity and complete reversal of dysplasia (CR-HGD) by 50 % at 5 years. 5-Aminolaevulinic acid (ALA) is an alternative treatment with non-randomised data suggesting 85 % CR-HGD and a low risk of side effects. We aimed to compare efficacy and side effect profile between the drugs. A single-centre randomised controlled trial was conducted. Presence of HGD was confirmed on three occasions by two specialist GI pathologists. Stratification was by length of BE and extent of dysplasia. Standard protocols for ALA and Photofrin-PDT were followed. Endoscopic follow-up with 2-cm four-quadrant biopsy was at 6 weeks, 4 months, and then annually. All adverse event data were collected. Sixty four patients were randomised, 34 ALA and 30 Photofrin-PDT. Median follow-up is 24 months. On intention-to-treat analysis, CR-HGD was 16/34 (47 %) with ALA-PDT and 12/30 (40 %) with Photofrin-PDT. The overall cancer incidence was 14 % (9/64). On sub-group log-rank analysis, for BE ≤6 cm, CR-HGD was significantly higher with ALA-PDT than Photofrin-PDT (χ2 = 5.39, p = 0.02). Strictures and skin photosensitivity were significantly more common after treatment with Photofrin-PDT than ALA-PDT (33 vs. 9 % and 43 vs. 6 %, respectively, p < 0.05). The rate of buried glands with either drug was significantly higher post-PDT (48 % of patients) than pre-PDT (20 %). ALA-PDT has a better risk profile than Photofrin-PDT. In patients with BE length ≤6 cm, preliminary results show ALA-PDT is associated with significantly higher CR-HGD. In longer segments of BE, neither PDT drug is sufficiently efficacious to warrant routine use.

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Acknowledgements

This work was undertaken at UCLH/UCL that received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. This work was also funded by a grant from Cancer Research UK to the UCL Experimental Cancer Medicine Centre. Aminolaevulinic acid was kindly supplied by Dr Stuart Marcus at DUSA Pharmaceuticals, NY.

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Authors and Affiliations

  1. National Medical Laser Centre, Division of Surgery and Interventional Science, University College London, 67-73 Riding House Street, London, W1W 7EJ, UK

    J. M. Dunn, G. D. Mackenzie, C. A. Mosse, R. Haidry, S. Green, S. Thorpe, S. G. Bown & L. B. Lovat

  2. Department of Histopathology, University College London, London, UK

    M. Rodriguez-Justo, A. Winstanley & M. R. Novelli

  3. Department of Gastroenterology, University College London Hospitals NHS Trust, London, UK

    M. R. Banks & L. B. Lovat

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  1. J. M. Dunn
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  2. G. D. Mackenzie
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  3. M. R. Banks
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  4. C. A. Mosse
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  5. R. Haidry
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  6. S. Green
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  7. S. Thorpe
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  8. M. Rodriguez-Justo
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  9. A. Winstanley
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  10. M. R. Novelli
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  11. S. G. Bown
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  12. L. B. Lovat
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Corresponding author

Correspondence to L. B. Lovat.

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Author contributions

JMD, GDM, SGB, LBL studied the concept and design; JMD, GDM, MRB, RH, ST, SG, MRG, AW, MN performed acquisition of data; JMD, GDM, LBL analysed and interpreted the data; JMD and LBL drafted the manuscript; GDM, MRB, CAM, SGB undertook critical revision of the manuscript for important intellectual content; JMD performed statistical analysis; CAM, SGB gave technical or material support; SGB, LBL obtained funding; and LBL supervised the study.

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Dunn, J.M., Mackenzie, G.D., Banks, M.R. et al. A randomised controlled trial of ALA vs. Photofrin photodynamic therapy for high-grade dysplasia arising in Barrett’s oesophagus. Lasers Med Sci 28, 707–715 (2013). https://doi.org/10.1007/s10103-012-1132-1

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  • DOI: https://doi.org/10.1007/s10103-012-1132-1

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