title: Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma.
abstract: BACKGROUND
  Bisphosphonates are used to prevent skeletal events of bone metastases, and may exhibit antitumour effects. We aimed to evaluate whether bisphosphonates can bring a response rate (RR), progression free survival (PFS) and overall survival (OS) benefit to patients with bone metastasis from renal cell carcinoma (RCC) that is treated with sunitinib.
  
  
  METHODS
  We performed a multicentre retrospective study of patients with bone metastases from RCC that was treated with sunitinib. The effect of bisphosphonates on RR, PFS and OS was tested with adjustment for known prognostic factors using a chi-square test from contingency table and partial likelihood test from Cox regression model.
  
  
  RESULTS
  Between 2004 and 2011, 209 patients with metastatic RCC were treated with sunitinib, 76 had bone metastases, 35 bisphosphonates users and 41 non-users. The groups of bisphosphonates users and non-users were balanced regarding known prognostic factors. Objective response was partial response/stable disease 86% (n = 30) versus 71% (n = 29), and progressive disease 14% (n = 5) versus 29% (n = 12) (p = 0.125, OR 2.48) in users versus non-users, respectively. Median PFS was 15 versus 5 months (HR = 0.55, p<0.0001), and median OS was not reached (with a median follow-up time of 45 months) versus 14 months (HR = 0.4, p = 0.029), in favour of users. In multivariate analysis of the entire patient cohort (n = 76), factors associated with PFS were bisphosphonates use (HR = 0.58, p = 0.035), and pre-treatment neutrophil to lymphocyte ratio >3 (HR = 3.5, p = 0.009). Factors associated with OS were bisphosphonates use (HR = 0.5, p = 0.008), elevated pre-treatment alkaline phosphatase (HR = 2.9, p = 0.003) and sunitinib induced HTN (HR = 0.63, p<0.0001).
  
  
  CONCLUSIONS
  Bisphosphonates may improve the RR, PFS and OS of sunitinib treatment in RCC with bone metastases.
authors.affiliation: Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Israel. danielkeizman@gmail.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Keizman
authors.forename: Maya
authors.initials: M
authors.lastname: Ish-Shalom
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Hans
authors.initials: H
authors.lastname: Hammers
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.forename: Victoria
authors.initials: V
authors.lastname: Sinibaldi
authors.forename: Ben
authors.initials: B
authors.lastname: Boursi
authors.forename: Natalie
authors.initials: N
authors.lastname: Maimon
authors.forename: Maya
authors.initials: M
authors.lastname: Gottfried
authors.forename: Henry
authors.initials: H
authors.lastname: Hayat
authors.forename: Avivit
authors.initials: A
authors.lastname: Peer
authors.forename: Svetlana
authors.initials: S
authors.lastname: Kovel
authors.forename: Avishay
authors.initials: A
authors.lastname: Sella
authors.forename: Raanan
authors.initials: R
authors.lastname: Berger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D004164:Diphosphonates / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage*; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D004164:Diphosphonates; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib