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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2011

01-11-2011 | Original Article

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)

Authors: Joyce M. van Dodewaard-de Jong, John M. H. de Klerk, Haiko J. Bloemendal, Bart P. J. van Bezooijen, Marie J. de Haas, Richard H. Wilson, Joe M. O’Sullivan

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2011

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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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Metadata
Title
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)
Authors
Joyce M. van Dodewaard-de Jong
John M. H. de Klerk
Haiko J. Bloemendal
Bart P. J. van Bezooijen
Marie J. de Haas
Richard H. Wilson
Joe M. O’Sullivan
Publication date
01-11-2011
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-011-1883-0

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