title: Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer.
abstract: Samarium-153 emits medium-energy beta particles and an imageable gamma photon with a physical half-life of 46.3 hr. When chelated to ethylenediaminetetramethylenephosphonic acid (EDTMP), it is remarkably stable in vitro and in vivo. In this study, we administered escalating amounts of 153Sm-EDTMP, from 0.1 to 1.0 mCi/kg (3.7-37 MBq/kg), to 22 patients with painful metastatic bone cancer. A complete concordance was found when the scintigrams of 153Sm-EDTMP were compared qualitatively to 99mTc-HDP bone images. Moreover, the skeletal uptake of the 153Sm-EDTMP related to the number of metastatic sites (r = 0.65; p = 0.001) showed an inverse proportion to the plasma radioactivity at 30 min following injection (r = -0.79; p = 0.0001) and was unaffected by the administered (mCi/kg), (r = 0.33; p = 0.13). Myelotoxicity was observed in 10 of the 29 treatment courses and leukopenia occurred in two. Thrombocytopenia occurred in patients who had low pretreatment platelet counts, albeit within the normal range (p = 0.001), most suffered from prostate cancer (p = 0.007) and retained a higher percentage of the 153Sm-EDTMP in their skeleton (p = 0.057). In four patients an exacerbation of the pre-existing pain ("flare reaction") was recorded. Pain palliation occurred in 65% of the treated patients (mean: 3.8 mo, range: 1-11 mo). Retreatment in first time responder patients was quite effective. Our preliminary results indicate that 153Sm-EDTMP is a promising radiotherapeutic agent for palliative treatment of metastatic bone cancer pain, and further study is necessary to ascertain its optimal dose, efficacy and toxicity.
authors.affiliation: Department of Medicine, University of Missouri-Columbia School of Medicine.
authors.forename: M
authors.initials: M
authors.lastname: Farhanghi
authors.forename: R A
authors.initials: RA
authors.lastname: Holmes
authors.forename: W A
authors.initials: WA
authors.lastname: Volkert
authors.forename: K W
authors.initials: KW
authors.lastname: Logan
authors.forename: A
authors.initials: A
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000503:physiopathology / Q000556:secondary*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology* / Q000532:radiotherapy; D010166:Palliative Care
chemical_list: D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C061972:samarium Sm-153 lexidronam