title: High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.
abstract: We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates.
authors.affiliation: Unit of Academic Radiotherapy and Clinical Oncology, Royal Marsden NHS Trust, Sutton, Surrey SM2 5PT, UK. drjoeosullivan@ireland.com
authors.forename: J M
authors.initials: JM
authors.lastname: O'Sullivan
authors.forename: V R
authors.initials: VR
authors.lastname: McCready
authors.forename: G
authors.initials: G
authors.lastname: Flux
authors.forename: A R
authors.initials: AR
authors.lastname: Norman
authors.forename: F M
authors.initials: FM
authors.lastname: Buffa
authors.forename: S
authors.initials: S
authors.lastname: Chittenden
authors.forename: M
authors.initials: M
authors.lastname: Guy
authors.forename: K
authors.initials: K
authors.lastname: Pomeroy
authors.forename: G
authors.initials: G
authors.lastname: Cook
authors.forename: J
authors.initials: J
authors.lastname: Gadd
authors.forename: J
authors.initials: J
authors.lastname: Treleaven
authors.forename: A
authors.initials: A
authors.lastname: Al-Deen
authors.forename: A
authors.initials: A
authors.lastname: Horwich
authors.forename: R A
authors.initials: RA
authors.lastname: Huddart
authors.forename: D P
authors.initials: DP
authors.lastname: Dearnaley
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary* / Q000628:therapy; D001842:Bone and Bones / Q000000981:diagnostic imaging; D003131:Combined Modality Therapy; D018450:Disease Progression; D012968:Etidronic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D011877:Radionuclide Imaging; D011878:Radiotherapy / Q000009:adverse effects; D011994:Recombinant Proteins; D012211:Rhenium / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D009942:Organometallic Compounds; D011994:Recombinant Proteins; C101598:rhenium-186 HEDP; D016179:Granulocyte Colony-Stimulating Factor; D012211:Rhenium; D017430:Prostate-Specific Antigen; D012968:Etidronic Acid; D000069585:Filgrastim