Concomitant oral tyrosine kinase inhibitors and bisphosphonates in advanced renal cell carcinoma with bone metastases

Br J Cancer. 2012 Nov 6;107(10):1665-71. doi: 10.1038/bjc.2012.385.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / secondary*
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / administration & dosage
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives
  • Osteonecrosis / chemically induced
  • Phenylurea Compounds / administration & dosage
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrroles / administration & dosage
  • Retrospective Studies
  • Sorafenib
  • Sunitinib
  • Treatment Outcome

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Indoles
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyrroles
  • Niacinamide
  • Sorafenib
  • Protein-Tyrosine Kinases
  • Sunitinib