title: A phase I study of 153Sm-EDTMP with fixed high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma.
abstract: Despite response rates of 30% after high-dose chemotherapy with autologous hematopoietic stem cell transplant, patients with multiple myeloma are not cured. 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP; Quadramet) is a short-range, beta-emitting therapeutic radiopharmaceutical with avid skeletal uptake. In total, 12 patients were treated with escalating doses of 153Sm-EDTMP (N=3/group; 6, 12, 19.8, and 30 mCi/kg) and a fixed dose of melphalan (200 mg/m(2)). No dose limiting toxicity was seen. To better standardize the marrow compartment radiation dose, the study was modified such that an additional six patients were treated at a targeted absorbed radiation dose to the red marrow of 40 Gy based on a trace labeled infusion 1 week prior to the therapy. Despite rapid elimination of unbound radiopharmaceutical via kidneys and bladder, no episodes of nephrotoxicity, hemorrhagic cystitis, or delayed radiation nephritis were observed with a median follow-up of 31 months (range 8.5-44). Median times to ANC>0.5 and platelet >20 x 10(6)/l were 12 and 11 days, respectively, with no graft failures. Overall response rate was 94% including seven very good partial responses and five complete responses. Addition of 153Sm EDTMP to melphalan conditioning appears to be safe, well-tolerated and worthy of further study.
authors.affiliation: Department of Internal Medicine, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. dispenzieri.angela@mayo.edu
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: G A
authors.initials: GA
authors.lastname: Wiseman
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: M R
authors.initials: MR
authors.lastname: Litzow
authors.forename: P M
authors.initials: PM
authors.lastname: Anderson
authors.forename: D A
authors.initials: DA
authors.lastname: Gastineau
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.forename: D J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: I N M
authors.initials: IN
authors.lastname: Micallef
authors.forename: S M
authors.initials: SM
authors.lastname: Ansell
authors.forename: L
authors.initials: L
authors.lastname: Porrata
authors.forename: M A
authors.initials: MA
authors.lastname: Elliott
authors.forename: J A
authors.initials: JA
authors.lastname: Lust
authors.forename: P R
authors.initials: PR
authors.lastname: Greipp
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: R
authors.initials: R
authors.lastname: Fonseca
authors.forename: T E
authors.initials: TE
authors.lastname: Witzig
authors.forename: C
authors.initials: C
authors.lastname: Erlichman
authors.forename: J A
authors.initials: JA
authors.lastname: Sloan
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D011868:Radioisotopes / Q000008:administration & dosage*; D012493:Samarium; D033581:Stem Cell Transplantation; D014018:Tissue Distribution; D019172:Transplantation Conditioning
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D012493:Samarium; C061972:samarium Sm-153 lexidronam; D008558:Melphalan