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).
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Meander Medical Centre, Postbox 1502, 3800 BM, Amersfoort, The Netherlands. jm.van.dodewaard@meandermc.nl
authors.forename: Joyce M
authors.initials: JM
authors.lastname: van Dodewaard-de Jong
authors.forename: John M H
authors.initials: JM
authors.lastname: de Klerk
authors.forename: Haiko J
authors.initials: HJ
authors.lastname: Bloemendal
authors.forename: Bart P J
authors.initials: BP
authors.lastname: van Bezooijen
authors.forename: Marie J
authors.initials: MJ
authors.lastname: de Haas
authors.forename: Richard H
authors.initials: RH
authors.lastname: Wilson
authors.forename: Joe M
authors.initials: JM
authors.lastname: O'Sullivan
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary*; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods*; D000077143:Docetaxel; D012968:Etidronic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D011879:Radiotherapy Dosage; D043823:Taxoids / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D043823:Taxoids; C101598:rhenium-186 HEDP; D000077143:Docetaxel; D012968:Etidronic Acid