Abstract
The aim of this study was to evaluate the efficacy of third-line combined androgen blockade (CAB) therapy for castration-resistant prostate cancer that relapsed after primary and second-line CAB. We retrospectively reviewed the medical records of 52 patients who received first-, second-, and third-line CAB therapy (medical or surgical castration, plus steroidal antiandrogen of chlormadinone acetate, or nonsteroidal antiandrogen of flutamide or bicalutamide). For cumulative analysis, we searched the PubMed database and identified a total of 50 cases published in English. Including our cases, this provided a total of 102 cases for analysis. In our study cohort, 11 cases (21.2%) achieved more than 50% reduction of serum prostate-specific antigen (PSA) on initiation of third-line CAB. We found that third-line CAB with nonsteroidal antiandrogen after second-line CAB with steroidal antiandrogen exhibited favorable results, with a positive response in six of 13 patients (46.2%). Cumulative analysis findings were comparable. Regarding the timing of third-line CAB administration, 15 patients had started at a PSA equal to or less than 4.0 ng/ml, and eight of them (53.3%) showed a positive response to treatment, compared to only three of 37 patients (8.1%) whose PSA at the initiation of third-line therapy was higher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB with nonsteroidal antiandrogen would be particularly useful for patients whose cancer progressed after second-line CAB with steroidal antiandrogen. The timing of treatment seems to be important because the higher the PSA at the start of third-line therapy, the lower the PSA response rate.
Highlights
Hormonal therapy has a well-defined role in patients who have metastatic prostate cancer and remains a mainstream treatment for their management, and even for localized prostate cancer the use of it has been widespread, especially among older patients (Situmorang et al, 2012)
We retrospectively reviewed the medical records of 52 patients who received first, second, and third-line combined androgen blockade (CAB) therapy
Several therapeutic strategies for hormonal therapy are used, such as an oral antiandrogen, a luteinizing hormone-releasing hormone (LH-RH) agonist, or surgical castration. Oral steroidal antiandrogens such as cyproterone acetate or chlormadinone acetate (CMA), or nonsteroidal antiandrogens such as flutamide (FLT), bicalutamide (BCL) or nilutamide (NIL) are administered to competitively block testosterone and/or dihydrotestosterone by binding to androgen receptors
Summary
Hormonal therapy has a well-defined role in patients who have metastatic prostate cancer and remains a mainstream treatment for their management, and even for localized prostate cancer the use of it has been widespread, especially among older patients (Situmorang et al, 2012). Several therapeutic strategies for hormonal therapy are used, such as an oral antiandrogen, a luteinizing hormone-releasing hormone (LH-RH) agonist, or surgical castration Oral steroidal antiandrogens such as cyproterone acetate or chlormadinone acetate (CMA), or nonsteroidal antiandrogens such as flutamide (FLT), bicalutamide (BCL) or nilutamide (NIL) are administered to competitively block testosterone and/or dihydrotestosterone by binding to androgen receptors. It is known that some patients with progressive disease who have undergone initial CAB therapy may respond to second-line CAB therapy with alternative antiandrogens (Scher et al, 1997; Joyce et al, 1998; Desai et al, 2001; Kojima et al, 2004; Miyake et al, 2005; Lam et al, 2006; Okihara et al, 2007; Nishimura et al, 2007; Suzuki et al, 2008; Okegawa et al, 2010; Choi et al, 2011) because the latter likely have different functional interactions with the androgen receptor.
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