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A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Bone-seeking radiopharmaceuticals have palliative benefit in castration-resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown improvement of survival and quality of life when radiopharmaceuticals were given repeatedly or in combination with chemotherapy. We designed a phase I study combining docetaxel and 186Re-labelled hydroxyethylidene diphosphonate (HEDP) in men with CRPC and bone metastases to evaluate toxicity.

Methods

A dose escalation schedule was designed consisting of four dose levels with a standard dosage of docetaxel (75 mg/m2 3-weekly). 186Re-HEDP was given in increasing activities (1,250 MBq up to 2,500 MBq) after the third and sixth cycle of docetaxel. Dose limiting toxicity (DLT) was defined as any grade 4 toxicity lasting more than 7 days or any grade 3 toxicity that did not recover within 10 days. Three patients were planned for each dose level expanding to six if a DLT occurred.

Results

Fourteen patients were recruited with a median age of 64.6 years. One DLT, grade 3 thrombocytopenia lasting >10 days, occurred at dose level 3 leading to expansion of this group to six. One of these patients had an episode of acute renal failure which resolved. Because of production problems of 186Re-HEDP dose level 4 was not started.

Conclusion

Combined therapy with docetaxel and 186Re-HEDP is generally well tolerated in patients with CRPC metastatic to bone. We will conduct a randomized phase II study using three cycles of docetaxel 75 mg/m2 3-weekly followed by 188Re-HEDP 40 MBq/kg body weight, followed by another three cycles of docetaxel 75 mg/m2, followed by 188Re-HEDP 20 MBq/kg body weight.

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Acknowledgements

This research was supported by unrestricted grants from Sanofi Aventis and Tyco Mallinckrodt. The staff working on this project in Belfast were supported through the UK Experimental Cancer Medicine Centre initiative. The Belfast Experimental Cancer Medicine Centre is supported by a programme grant from Cancer Research UK and the N. Ireland Health and Social Care Research and Development Division. We are grateful to the staff in both our sites for their help. Above all, we thank our patients, their families and friends for their support and participation in this clinical trial.

Conflicts of interest

Joe M. O’Sullivan and Richard H. Wilson received honoraria from Sanofi Aventis. In addition as the principal investigator Joe M. O'Sullivan received research funding from Sanofi Aventis and Mallinckrodt/Covidien. The other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Meander Medical Centre, Postbox 1502, 3800 BM, Amersfoort, The Netherlands

    Joyce M. van Dodewaard-de Jong & Haiko J. Bloemendal

  2. Department of Nuclear Medicine, Meander Medical Centre, Postbox 1502, 3800 BM, Amersfoort, The Netherlands

    John M. H. de Klerk & Marie J. de Haas

  3. Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Lisburn Road, Belfast, BT9 7AB, N. Ireland, UK

    Richard H. Wilson & Joe M. O’Sullivan

  4. Department of Urology, Meander Medical Centre, Postbox 1502, 3800 BM, Amersfoort, The Netherlands

    Bart P. J. van Bezooijen

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  1. Joyce M. van Dodewaard-de Jong
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Correspondence to Joyce M. van Dodewaard-de Jong.

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van Dodewaard-de Jong, J.M., de Klerk, J.M.H., Bloemendal, H.J. et al. A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial). Eur J Nucl Med Mol Imaging 38, 1990–1998 (2011). https://doi.org/10.1007/s00259-011-1883-0

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  • DOI: https://doi.org/10.1007/s00259-011-1883-0

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