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. 2011 Nov;38(11):1990-8. doi: 10.1007/s00259-011-1883-0. Epub 2011 Jul 27.


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 (186)Re-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/m(2) 3-weekly). (186)Re-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 (186)Re-HEDP dose level 4 was not started.

Conclusion: Combined therapy with docetaxel and (186)Re-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/m(2) 3-weekly followed by (188)Re-HEDP 40 MBq/kg body weight, followed by another three cycles of docetaxel 75 mg/m(2), followed by (188)Re-HEDP 20 MBq/kg body weight.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Neoplasms / secondary*
  • Chemoradiotherapy / adverse effects*
  • Chemoradiotherapy / methods*
  • Docetaxel
  • Etidronic Acid / adverse effects*
  • Etidronic Acid / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Orchiectomy*
  • Organometallic Compounds / adverse effects*
  • Organometallic Compounds / therapeutic use
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Prostatic Neoplasms / therapy*
  • Radiotherapy Dosage
  • Taxoids / adverse effects*
  • Taxoids / therapeutic use
  • Treatment Outcome


  • Organometallic Compounds
  • Taxoids
  • rhenium-186 HEDP
  • Docetaxel
  • Etidronic Acid