New Directions in the Management of Advanced Prostate Cancer

Introduction

RIUS0000(Watson)_02-14.qxd 2/14/07 6:47 PM Page S1 INTRODUCTION New Directions in the Management of Advanced Prostate Cancer Herbert Lepor, MD Department of Urology, New York University School of Medicine, New York, NY [Rev Urol. 2007;9(suppl 1):S1-S2] © 2007 MedReviews, LLC pproximately 70 years ago, Huggins and Hodges1 reported the benefits of androgen-deprivation therapy for advanced prostate cancer. The dramatic palliation associated with androgen deprivation did not require randomized, double-blind, placebo-controlled trials to convince urologists of their clinical utility. Since that time, androgen-deprivation therapy has continued to represent the first-line treatment for advanced prostate cancer. We have seen the development of different ways to achieve androgen deprivation that are more convenient and better tolerated but no better at increasing survival. Twenty-five years ago, the Department of Urology at Johns Hopkins Hospital and several other academic institutions were active participants in the National Prostate Cancer Project (NPCP). As Hopkins residents, we were intimately involved with the NPCP-sponsored programs that were investigating several prostate chemotherapy trials. Multiple trials failed to demonstrate any clinical or survival advantage. The future for androgen-insensitive prostate cancer was A VOL. 9 SUPPL. 1 2007 REVIEWS IN UROLOGY S1 RIUS0000(Watson)_02-14.qxd 2/22/07 2:23 AM Page S2 Introduction continued bleak, at best. Disease recurrence while on androgen deprivation was a death sentence. We have made modest strides in the management of androgen-insensitive prostate cancer over the past 25 years. The addition of antiandrogens to gonadotropin-releasing hormone (GnRH) agonists and secondary hormonal therapy options has yielded incremental benefits for some men. One of the limitations of long-term androgen deprivation therapy is bone loss, which exacerbates the risk of pathological fractures. Intravenous biphosphonates decrease bone loss in men with androgen deprivation, resulting in fewer skeletal-related events and diminished bone pain. These are modest advances, but represent some progress in a field that yielded no advances for decades. The combination of docetaxel and estramustine was recently shown to increase survival by 2 months over the combination of mitoxantrone and prednisone in men with androgeninsensitive prostate cancer.2 Some consider this benefit clinically irrelevant. For the men with androgeninsensitive prostate cancer, an extension of survival by 25% is likely to be important. Taxanes will assume an S2 VOL. 9 SUPPL. 1 2007 important role in the management of advanced prostate cancer, but the urologist and medical oncologist need more and better alternatives. It is possible that someday the right chemotherapeutic regimen will be identified for prostate cancer. I am not optimistic, however, as multiple trials with virtually every agent have yielded no benefits. There is tremendous interest in developing immune and gene therapies for prostate cancer. One of the advantages of these options is that they are fairly well tolerated. Several immune and gene therapies are advancing through the FDA approval process. While these approaches are still investigational, the urologist should be familiar with both their mechanisms of action and the preliminary clinical data available. This supplement for Reviews in Urology provides a comprehensive overview of the management of advanced prostate cancer. It is a mustread supplement for all urologists taking care of men with advanced prostate cancer. Herbert Lepor, MD, and Mark A. Perlmutter, MD, focus on primary and secondary hormonal therapy. Prateek Mendiratta, MD, Andrew J. Armstrong, MD, and Daniel J. REVIEWS IN UROLOGY George, MD, discuss the latest advances in chemotherapy, highlighting the new clinical information on docetaxel and giving us a glimpse of new treatment options under investigation. Matthew A. Stanizzi, MD, and Simon J. Hall, MD, present the rationale and strategy for gene therapy. And Johannes Vieweg, MD, focuses on immune-based therapies, discussing the rationale for treatment and providing a clinical update. I am grateful for the timely and scholarly contributions of our invited experts. We are fortunate to have engaged Drs. George, Hall, and Vieweg to contribute to this supplement, as these individuals are internationally recognized authorities in their respective fields and have their finger on the pulse of where the field of androgen-insensitive prostate cancer is heading. References 1. 2. Huggins C, Hodges CV. Studies on prostatic cancer, I: the effect of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1:293-297. Petrylak DP, Tangen CM, Hussain MHA, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Eng J Med. 2004;351:15131520.