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A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers

  • PHASE II STUDIES
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Summary

The prognosis of advanced biliary tract carcinoma is poor with chemotherapy limited to a palliative role. This randomised study was designed to evaluate the effectiveness of a new liposomal thymidylate synthase inhibitor (TSI), OSI-7904L, in parallel with a modified de Gramont regimen of 5-FU/LV in patients with advanced biliary cancer. Patients with previously untreated advanced or metastatic carcinoma of the biliary tract were randomised to receive either OSI-7904L 12 mg/m2 intravenously every 21 days or a modified de Gramont schedule of 5-FU/LV (intravenous l-LV 200 mg/m2, bolus 5-FU 400 mg/m2 and a 46-h infusion of 5-FU 2,400 mg/m2) every 14 days. Twenty-two patients were randomised, 11 to each group. No patients responded in the OSI-7904L arm, while one patient achieved a partial response in the 5-FU/LV arm. The rates of disease stabilisation were 4/11 (OSI-7904L) and 10/11 (5-FU/LV). Both treatment arms were generally well tolerated. These results show that the activity of OSI-7904L is below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilisation. A simplified de Gramont schedule appears to have marginally more activity. Both treatments were well tolerated.

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Acknowledgments

The authors would like to thank the patients who consented to take part in this study. In addition, the following people for their contributions: Prof E Van Cutsem for input to the original protocol design; Dr K Richardson for the genotype sample analyses; D Zborowski for additional analyses.

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Authors and Affiliations

  1. Oncology Institute “Ion Chiricuta”, 34–36 Gh. Bilascu Street, 3400, Cluj-Napoca, Romania

    T. Ciuleanu

  2. Institutul Clinic Fundeni, Centrul de Gastroenterologie si Hepatologie, Sos Fundeni nr. 258, Sector 2, 72437, Bucuresti, Romania

    M. Diculescu

  3. Klinikum der J.W. Groethe-Universität, Theodor Stern Kai 7, 60590, Frankfurt, Germany

    N. M. Hoepffner & J. Trojan

  4. Universitätsklinik Essen, Tumorforschung, Hufeland Str. 55, 45122, Essen, Germany

    V. Sailer

  5. University of Michigan, Ann Arbor, MI, USA

    M. Zalupski

  6. Innere Medizin IV, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    T. Herrmann

  7. Oncosurger, HUG, 24 Micheli-du-Crest, 1211, Geneva 14, Switzerland

    A. Roth

  8. OSI Pharmaceuticals, Watlington Road, Cowley, Oxford, OX4 6LT, UK

    J. Chick & K. Brock

  9. OSI Pharmaceuticals, 2860 Wilderness Place, Boulder, CO, 80301, USA

    D. Albert

  10. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    P. A. Philip

Authors
  1. T. Ciuleanu
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  2. M. Diculescu
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  3. N. M. Hoepffner
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  4. J. Trojan
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  5. V. Sailer
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  6. M. Zalupski
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  7. T. Herrmann
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  8. A. Roth
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  9. J. Chick
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  10. K. Brock
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  11. D. Albert
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  12. P. A. Philip
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Corresponding author

Correspondence to T. Ciuleanu.

Additional information

Research funding and OSI-7904L provided by OSI Pharmaceuticals Inc.

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Ciuleanu, T., Diculescu, M., Hoepffner, N.M. et al. A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers. Invest New Drugs 25, 385–390 (2007). https://doi.org/10.1007/s10637-007-9040-0

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  • DOI: https://doi.org/10.1007/s10637-007-9040-0

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