Phase II study of fulvestrant (faslodex®) in castration resistant prostate cancer

Abstract

Fulvestrant was well tolerated but failed to produce clinical or PSA response in men with CRPC.

Estrogen receptor beta in prostate cancer: friend or foe?

“…The underlying reasons for this necessitate further investigation. One possibility is insufficient dosing of the therapeutic agents in question (Chadha et al 2008 Nakajima et al (2011) primary human tissue culture (Centenera et al 2012) or xenografts of human tumours (Lawrence et al 2013) may be helpful in this regard. Estrogen-related pathways are clearly of great importance in the development and progression of hormonedependent cancers such as prostate cancer, but the role of ERB remains controversial, with numerous contradictions in the published literature.…”

“…Fulvestrant, an ERA antagonist, has been shown to be effective in preclinical models with growth inhibition of prostate cancer cell lines (Lau et al 2000, Leung et al 2006a. However, in a phase 2 study of 20 men with CRPC, fulvestrant failed to produce either a clinical or biochemical (PSA) response (Chadha et al 2008). Similarly, tamoxifen, a mixed ERA agonist/antagonist has been shown to be ineffective in men with CRPC (Bergan et al 1999) despite inhibiting the growth of prostate cancer cell lines in preclinical studies (Rohlff et al 1998).…”

PSA Decrease with Fulvestrant Acetate in a Hormone-Resistant Metastatic Prostate Cancer Patient

“…The observed activity is exciting. Any relevantsideeffectshavebeenrecordedfollowingtheadverse effects reported by the group of Chadha et al [15] in their phaseIItrial.Thisgroupdidnotdescribeanyrelevanttoxicity in any of their recruited patients. Under the view of this reportedactivityweconsideritjustifiedtocontinuewiththe investigation of fulvestrant in patients with advanced PCa, and the inclusion of fulvestrant in the design of future trials for the treatment of PCa.…”

“…[14]publishedinterestingresultstreatingPCa celllineswithfulvestrant.A70%growthinhibitionwasseen inandrogen-stimulatedLNCaPcells,showingthatfulvestrant isapotentARdownregulatorthatcanproducesignificantinhibitionofPCacellgrowth.AphaseIItrialwasrecentlypublished with the use of fulvestrant in castration-resistant PCa patients,andnoevidenceofactivitywasdetected [15].…”

Do We Really Need New Trials on Fulvestrant in Prostate Cancer?

“…Theauthorsrefertoaphase2trialonfulvestrantwhichactu-allyfailedtodemonstrateanyactivityofthisdrug [4].Thisstudy was well designed and well conducted. All 20 eli gible patients hadtrueCRPC,and16hadmeasurabledisease.TherewereneitherobjectiveresponsesnorasignificantserumPSAdeclineaccordingtocurrentPSAresponsecriteria [5].Thus,itisveryunOnkologie2010;33:12-13 DoWeReallyNeedNewTrialsonFulvestrant inProstateCancer?…”