title: Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer: A Multicenter Phase 1 Study.
abstract: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).
  
  
  
  Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts.
  
  
  
  No DLT's were observed and as pre-specified, the highest dose administered was defined as MTD. In total, 206 adverse events (AE) were recorded and 13,6% were classified as treatment-related, while none were serious or severe (SAE). No cumulative toxicity and no renal toxicity were recorded.
  
  
  
  ODX was well tolerated, with few and mild side-effects and with apparent treatment efficacy in the highest dose cohort. Further clinical development is currently in progress.
authors.affiliation: Norrlands University Hospital, Umeå, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Thellenberg-Karlsson
authors.affiliation: Stockholm South General Hospital, Stockholm, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Nyman
authors.affiliation: Karolinska Institute, CCK/R8/00, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Skånes University Hospital, Lund, Sweden.
authors.forename: René
authors.initials: R
authors.lastname: Blom
authors.affiliation: Karolinska Institute, CCK/R8/00, Stockholm, Sweden.
authors.forename: Marcela
authors.initials: M
authors.lastname: Márquez
authors.affiliation: Karolinska Institute, CCK/R8/00, Stockholm, Sweden.
authors.forename: Enrique
authors.initials: E
authors.lastname: Castellanos
authors.affiliation: Karolinska Institute, CCK/R8/00, Stockholm, Sweden arh@telia.com.
authors.forename: Anders R
authors.initials: AR
authors.lastname: Holmberg
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates
keywords: CRPC; Polybisphosphonate; bone-targeting; cytotoxic; metastasis