Leukopenia as a risk factor for osteonecrosis of the jaw in metastatic prostate cancer treated using zoledronic acid and docetaxel

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Abstract
Study Type – Harm (case series) Level of Evidence 4 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. MATERIALS AND 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 P = 0.030) as independent risk factors. CONCLUSION: 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.

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