title: Concomitant oral tyrosine kinase inhibitors and bisphosphonates in advanced renal cell carcinoma with bone metastases.
abstract: BACKGROUND
  The presence of bone metastases in patients with metastatic renal cell carcinoma treated with oral tyrosine kinase inhibitors (TKIs) is associated with poorer outcome as compared with patients without bone involvement. Concomitant bisphosphonates could probably improve outcomes but also induce osteonecrosis of the jaw (ONJ).
  
  
  METHODS
  Retrospective study on all the renal cell carcinoma patients with bone metastases treated with sunitinib or sorafenib between November 2005 and June 2012 at the University Hospitals Leuven and AZ Groeninge in Kortrijk.
  
  
  RESULTS
  Seventy-six patients were included in the outcome analysis: 49 treated with concomitant bisphosphonates, 27 with TKI alone. Both groups were well balanced in terms of prognostic and predictive markers. Response rate (38% vs 16% partial responses, P=0.028), median progression-free survival (7.0 vs 4.0 months, P=0.0011) and median overall survival (17.0 vs 7.0 months, P=0.022) were significantly better in patients receiving bisphosphonates. The incidence of ONJ was 10% in patients treated with TKI and bisphosphonates.
  
  
  CONCLUSIONS
  Concomitant use of bisphosphonates and TKI in renal cell carcinoma patients with bone involvement probably improves treatment efficacy, to be confirmed by prospective studies, but is associated with a high incidence of ONJ.
authors.affiliation: Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Herestraat 49, Herestraat 49, B-3000 Leuven, Belgium. benoit.beuselinck@uzleuven.be
authors.forename: B
authors.initials: B
authors.lastname: Beuselinck
authors.forename: P
authors.initials: P
authors.lastname: Wolter
authors.forename: A
authors.initials: A
authors.lastname: Karadimou
authors.forename: R
authors.initials: R
authors.lastname: Elaidi
authors.forename: H
authors.initials: H
authors.lastname: Dumez
authors.forename: A
authors.initials: A
authors.lastname: Rogiers
authors.forename: T
authors.initials: T
authors.lastname: Van Cann
authors.forename: L
authors.initials: L
authors.lastname: Willems
authors.forename: J-J
authors.initials: JJ
authors.lastname: Body
authors.forename: J
authors.initials: J
authors.lastname: Berkers
authors.forename: H
authors.initials: H
authors.lastname: Van Poppel
authors.forename: E
authors.initials: E
authors.lastname: Lerut
authors.forename: P
authors.initials: P
authors.lastname: Debruyne
authors.forename: R
authors.initials: R
authors.lastname: Paridaens
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010020:Osteonecrosis / Q000139:chemically induced; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib