title: Leukopenia as a risk factor for osteonecrosis of the jaw in metastatic prostate cancer treated using zoledronic acid and docetaxel.
abstract: What's known on the subject? and What does the study add? The common clinical practice for advanced prostatic adenocarcinoma is combination therapy of zoledronic acid (ZA) and docetaxel (TAX). Little is known about the consequences of this combination therapy with regard to osteonecrosis of the jaw (ONJ). This study shows that the combination therapy of ZA and TAX increases the risk of ONJ and that tooth extraction and leukopenia induced by TAX are the risk factors.
  
  
  OBJECTIVE
  • To determine whether docetaxel (TAX) can increase the risk of osteonecrosis of the jaw (ONJ) in patients with prostatic adenocarcinoma (PC) receiving zoledronic acid (ZA), a bisphosphonate (BP) used in the treatment of patients with cancer.
  
  
  METHODS
  • The medical records of 111 patients with PC who received ZA between September 2006 and March 2011 at our institutions were reviewed to assess the incidence and risk factors for ONJ.
  
  
  RESULTS
  • Nine patients (8.1%) developed ONJ during a median follow-up of 14.5 months. • Using univariate analysis we found that TAX chemotherapy (P=0.037, hazard ratio [HR] 6.611), tooth extraction during ZA therapy (P<0.001, HR 11.254), and high prostate-specific antigen level (P=0.019, HR 8.008) at the start of ZA were predictive factors. • Using multivariate analysis we found that TAX chemotherapy (P=0.011, HR 56.35), steroid use (P=0.044, HR = 17.795), and tooth extraction (P=0.039, HR 7.471) were independent predictors. •  Among those receiving TAX chemotherapy, multivariate analysis identified tooth extraction (P=0.009) and nadir WBC counts <1000/µL during TAX chemotherapy (P=0.030) as independent risk factors.
  
  
  CONCLUSIONS
  •  Tooth extraction and nadir WBC counts <1000/µL were found to be risk factors for ONJ in metastatic prostate cancer treated with ZA and TAX combination therapy, showing that leukopenia is an important factor in the development of ONJ.
authors.affiliation: Department of Urology, the University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.forename: Motofumi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Enomoto
authors.forename: Akira
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hirano
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary*; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D007573:Jaw Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000556:secondary*; D007970:Leukopenia / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000139:chemically induced* / Q000453:epidemiology; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D043823:Taxoids / Q000009:adverse effects* / Q000627:therapeutic use; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid