title: A phase I study of samarium lexidronam/bortezomib combination therapy for the treatment of relapsed or refractory multiple myeloma.
abstract: OBJECTIVE
  This open-label, phase I dose-escalation study assessed the safety, tolerability, and initial efficacy of Samariam 153 (153Sm)-lexidronam/bortezomib combination therapy for patients with relapsed/refractory multiple myeloma.
  
  
  METHODS
  Patients were enrolled in six cohorts and given bortezomib (1.0 or 1.3 mg/m2) on days 1, 4, 8, and 11 and 153Sm-lexidronam (0.25, 0.5, or 1.0 mCi/kg) on day 3 of a 56-day cycle (maximum of four cycles). The primary endpoints were safety and tolerability of the 153Sm-lexidronam/bortezomib regimen.
  
  
  RESULTS
  Twenty-four patients were enrolled. Median values for age, time since diagnosis, and number of prior treatments were 63 years, 29 months, and three regimens, respectively. The most common toxicities were hematologic; during the first cycle, median neutrophil and platelet nadirs were 1,000/mm3 and 98,500/mm3, respectively, and observed generally 3 to 4 weeks post-treatment. The incidences of grade 4 neutropenia and thrombocytopenia were 12.5% and 8.3%, respectively, during treatment cycle 1. Dose-limiting toxicity, reached in cohort 6 as a result of hematologic toxicity, defined the maximum tolerated dose as 0.5 mCi/kg 153Sm-lexidronam in combination with 1.3 mg/m2 bortezomib. The maximum tolerated dose for 153Sm-lexidronam in combination with the 1.0 mg/m2 bortezomib was not reached. No nonhematologic dose-limiting toxicities were observed; both the incidence and the severity of peripheral neuropathy were low. Responses occurred in 5 (21%) patients, including 3 (12.5%) complete and 2 (8.3%) minimal responses.
  
  
  CONCLUSIONS
  Bortezomib combined with 153Sm-lexidronam appears to be a well-tolerated regimen, which showed clinical activity in this phase I trial for patients with relapsed or refractory multiple myeloma.
authors.affiliation: Institute for Myeloma & Bone Cancer Research, West Hollywood, CA 90069, USA. jberenson@imbcr.org
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.forename: Ori
authors.initials: O
authors.lastname: Yellin
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Herb
authors.initials: H
authors.lastname: Duvivier
authors.forename: Youram
authors.initials: Y
authors.lastname: Nassir
authors.forename: Russell
authors.initials: R
authors.lastname: Mapes
authors.forename: Christina DiLauro
authors.initials: CD
authors.lastname: Abaya
authors.forename: Regina A
authors.initials: RA
authors.lastname: Swift
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005029:Ethylenediamines / Q000008:administration & dosage*; D006801:Humans; D020714:Maximum Tolerated Dose; D009101:Multiple Myeloma / Q000628:therapy*; D063065:Organophosphonates / Q000008:administration & dosage*; D010976:Platelet Count; D011719:Pyrazines / Q000008:administration & dosage*; D011868:Radioisotopes / Q000008:administration & dosage*; D012008:Recurrence; D012493:Samarium / Q000008:administration & dosage*
chemical_list: D001897:Boronic Acids; D005029:Ethylenediamines; D063065:Organophosphonates; D011719:Pyrazines; D011868:Radioisotopes; C418473:ethylenediaminetetrakis(methylphosphonic) acid; D012493:Samarium; D000069286:Bortezomib