A Changing Landscape in Castration-Resistant Prostate Cancer Treatment

A Felici,Paolo Carlini,M S Pino

doi:10.3389/fendo.2012.00085

Abstract

Prostate cancer (PC) is the leading cause of cancer and the second leading cause of cancer-death among men in the Western world. About 10–20% of men with PC present with metastatic disease at diagnosis, while 20–30% of patients diagnosed with localized disease will eventually develop metastases. Although most respond to initial androgen-deprivation therapy (ADT), progression to castration-resistant PC (CRPC) is universal. In 2004 the docetaxel/prednisone regimen was approved for the management of patients with metastatic CRPC, becoming the standard first-line therapy. Recent advances have now led to an unprecedented number of new drug approvals within the past years, providing many new treatment options for patients with metastatic CRPC. Four new drugs have received U.S. Food and Drug Administration (FDA)-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. The data supporting the approval of each of these agents are described in this review, as are current approaches in the treatment of metastatic CRPC and ongoing clinical trials of novel treatments and strategies.

Highlights

Prostate cancer (PC) is the leading cause of cancer and the second leading cause of cancer-death among men in the Western world (Siegel et al, 2012)
The availability of multiple new treatments in patients with metastatic castration-resistant prostate cancer (CRPC) is the current challenge for the clinicians, facing the choice of the right treatment at the right time (Figure 1)
Symptomatic patients would be probably better served with chemotherapy as sipuleucel-T administration leads to almost no response, as well as time to progression (TTP) is not affected

Summary

INTRODUCTION

Prostate cancer (PC) is the leading cause of cancer and the second leading cause of cancer-death among men in the Western world (Siegel et al, 2012). Current approaches in CRPC treatment different mechanisms of action have demonstrated efficacy, and in 2012 therapeutic options for patients with metastatic CRPC include four new agents approved by the U.S Food and Drug Administration (FDA) in 2010 and 2011 These new agents are an immunotherapeutic product (sipuleucel-T), for the treatment of asymptomatic or minimally symptomatic metastatic CRPC patients; a novel taxane, cabazitaxel, which showed a survival advantage over mitoxantrone in docetaxel-pretreated patients; an androgen synthesis inhibitor, abiraterone acetate, which was reported to improve survival when evaluated against placebo in docetaxel-pretreated patients; and a bone-targeting agent (denosumab; Table 1). A larger, double blind, placebo-controlled, multicenter phase III study, the IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) was subsequently conducted in 512 patients with asymptomatic or minimally symptomatic metastatic CRPC with OS as the primary endpoint (Kantoff et al, 2010a). TAX327 (Tannock et al, 2004; Berthold et al, 2008) IMPACT (Kantoff et al, 2010a) TROPIC (de Bono et al, 2010) COU-AA-301 (de Bono et al, 2011) ALSYMPCA (Parker et al, 2012b)

CRPC population

Findings

CONCLUSIONS