Zoledronic Acid Administration in Aggressive Castration- Resistant Prostate Cancer

Dear EditorBone metastases alone or in combination withandrogen deprivation therapy-related bone loss placesprostate cancer patients at great risk of skeletal morbidity,including pain and fracture. Thus patient’s quality of lifemay be significantly impaired. One approach to controlis through use of zoledronic acid (ZA), an intravenouslyapplied bisphosphonate approved for the prevention andtreatment of cancer skeletal-related events. However, ZAmay also act by other mechanismsWe have experienced positive effects in a 65-year-oldman who underwent retropubic radical prostatectomywith localized prostate cancer (PC) in 2004. Pathologicalexamination revealed metastatic PC (pT3a pN1 M0, GS4+3=7), and therefore androgen deprivation therapy(ADT) with goserelin was initiated. From October 2006an AD agent, bicalutamide was added because of abiochemical failure. Alternative ADT including flutamide,estramusutine phosphate, chlormadinone acetate, andbicaltamide was initiated according to our institutionalcriteria. However, PSA levels rapidly increased markedly(Figure 1A). During the switch of anti-androgen agentswe checked an androgen withdrawal syndrome.Although dexamethasone (DXM) therapy wasstarted for aggressive castration-resistant prostate cancer(CRPC), PSA levels rose and radiological examinationsrevealed swelling of the para-aortic and para-inferior venacava lymph nodes and tiny bone metastasis. Monthlyadministration of zoledronic acid (ZA) was then initiatedin August 2008. PSA levels decreased greatly overthe next two years (see Figure 1A). ZA and goserelinadministration have now maintained PSA levels below 0.2ng/ml for 3 years. The para-aortic lymph node reduced insize and the para-inferior vena cava lymph node swellingdisappeared (Figure 1B). DXM was gradually tapered offby June 2010.ZA has been shown to block multiple steps in tumormetastases (e.g. angiogenesis, invasion, adhesion, andproliferation) in preclinical and translational studies(Gnant, 2011). A recent Austrian Breast and ColorectalCancer Study Group trial demonstrated significantlyimproved in disease-free survival rates after adjuvantadministration of ZA for breast cancer (Gnant et al.,2011). Several studies have suggested that the potentialanticancer activity of ZA in PC. For example, ZAadministration improved PSA levels in a case of CRPCwith bone and lymph nodes metastases (Kikuno etal., 2007). According to Prostate Cancer Nomograms:Hormone Refractory by Memorial Sloan-Kettering CancerCenter, survival probabilities for this patient after 1 and2 years were estimated to be 73 % and 35 % respectively(median, 18 months) (Cho et al., 2003). However, in ourpresent case relapse-free survival with low PSA levels andreduced lymph nodes were maintained for 3 years afterZA administration.In conclusion, ZA administration may greatlycontribute to increased survival in patients with aggressiveCRPC and not only through action against.developmentof bone metastases