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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Advances in the Understanding and Treatment of Prostate Cancer


GOAL
To provide oncologists with an overview of the current treatments available for androgen-independent prostate cancer.

TARGET AUDIENCE
This activity is designed for oncologists. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, the participant should be able to:

  • Evaluate the current treatments and the role of the selective endothelin receptor antagonist in the management of androgen-independent prostate cancer.
  • Assess the results of the phase III atrasentan meta-analysis, particularly with regard to bone pain in androgen-independent prostate cancer.
  • Discuss the significance of a decrease in the incidence and onset of pain in patients with androgen-independent prostate cancer.
  • Identify the most appropriate patient for treatment with a selective endothelin
    receptor antagonist.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
The estimated time to complete this educational activity: 2 hours.

Release date: April 15, 2006.
Expiration date: April 15, 2008.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Abbott Laboratories.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Directors and Participating Faculty reported the following:

PROGRAM DIRECTORS

Michael A. Carducci, MD
Associate Professor of Oncology and Urology
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Carducci reports serving as a consultant for Abbott Laboratories, Centocor, CuraGen, MethylGene, and Sanofi-Aventis; and receiving honoraria from Abbott Laboratories and Sanofi-Aventis.
Samuel R. Denmeade, MD
Associate Professor of Oncology
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Denmeade reports having no financial or advisory relationships with corporate organizations related to this activity.

PARTICIPATING FACULTY

Philip W. Kantoff, MD
Director, The Lank Center for Genitourinary Oncology
Chief, Division of Solid Tumor Oncology
Dana-Farber Cancer Institute
Professor of Medicine
Harvard University Medical School
Boston, Massachusetts
Dr Kantoff reports serving on the advisory board of Abbott Laboratories, Amgen, ArQule, AstraZeneca, Bristol-Meyers Squibb Company, Celgene, Glycogenesis, OSI, Pfizer Inc, Sanofi-Aventis, TAP, and Watson Pharma; and receiving grants/research support from Amgen, Bayer, Bristol-Myers Squibb Company, Genentech, Genzyme, GlaxoSmithKline, Novartis, Pfizer Inc,
Therion Biologics, and Wilex.

Joel B. Nelson, MD
Professor and Chairman of Urology
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
Dr Nelson reports receiving grants/research support from Abbott Laboratories; and serving as a consultant for Abbott Laboratories.

Daniel P. Petrylak, MD
Associate Professor of Medicine
New York Presbyterian Hospital 
Columbia University Medical Center
New York, New York
Dr Petrylak reports receiving grants/research support from Abbott Laboratories, Celgene, Eli Lilly and Company, GPC Biotech, and Sanofi-Aventis; serving as a consultant for Celgene, Cell Genesys, Eli Lilly and Company, GPC Biotech, and Sanofi-Aventis; and receiving honoraria from Celgene, Eli Lilly and Company, and Sanofi-Aventis. 

A. Oliver Sartor, MD
Director, Stanley S. Scott Cancer Center
Chief, Hematology/Oncology
Louisiana State University Health Sciences Center New Orleans
New Orleans, Louisiana
Dr Sartor reports serving as a consultant for Abbott Laboratories, Cytogen, and GPC Biotech.


Notice: The audience is advised that articles in this CME activity contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Drs Carducci, Nelson, Petrylak, and Sartor—atrasentan in prostate cancer.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Advances In The Understanding And Treatment Of Prostate Cancer
Michael A. Carducci, MD, and Samuel R. Denmeade, MD 

In the United States, prostate adenocarcinoma is the most common noncutaneous malignancy in men and the second leading cause of cancer death.1 More than 29 000 men die of prostate cancer annually in the United States, largely because androgen deprivation therapy (ADT) fails to control their disease.2,3

For men with metastatic prostate cancer, androgen blockade has been the mainstay of treatment since the observation by Huggins and Hodges that castration caused tumor regression.4 Although 80% of patients initially respond to ADT and achieve stabilization or regression of disease, virtually all progress to an androgen-independent, refractory state over varying periods of time.5 Today, ADT is being used in patients at an earlier stage of disease (ie, concomitant with radiation therapy; in patients with prostate-specific antigen [PSA] relapse after primary therapy; and in patients at high risk of recurrence, defined as those with stage T3—4 disease, Gleason score >=8, or PSA >20).5 This earlier implementation of ADT is a factor contributing to the greater median duration (10.8 years) of hormonal response reported in a recent study, compared with the less than 2-year duration of response for men with metastatic disease.5,6

With earlier ADT initiation, the time to hormone-refractory disease varies considerably.5,6 Extent of disease at the time of development of hormone-refractory disease can range from an asymptomatic rise in PSA without metastasis to symptomatic metastatic bone disease. Once hormone-refractory prostate cancer becomes metastatic, as defined by radiographic criteria, approximately 90% of patients will have osteoblastic metastases.7 The increasing population of men with hormone-refractory disease makes the development of effective posthormonal therapeutic alternatives a top priority.

This issue of Johns Hopkins Advanced Studies in Medicine will highlight the current treatment options for androgen-independent prostate cancer. It will also include a discussion of selective endothelin receptor antagonists in the management of patients with prostate cancer with bony metastatic disease, and identification of the most appropriate patient for clinical trials with a selective endothelin receptor antagonist. Additionally, this monograph will define the roles of the urologist and oncologist in the management of bone pain in androgen-independent prostate cancer.

REFERENCES

1. Jemal A, Murray T, Samuels A, et al. Cancer statistics, 2003. CA Cancer J Clin. 2003;53:5-26.
2. American Cancer Society. Cancer statistics 2005: a presentation from the American Cancer Society. American Cancer Society, Inc. 2005.
3. Nelson JB, Nabulsi AA, Vogelzang NJ, et al. Suppression of prostate cancer induced bone remodeling by the endothelin receptor A antagonist atrasentan. J Urol. 2003;169:1143-1149.
4. Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. J Urol. 2002;168:9-12.
5. Kish JA, Bukkapatnam R, Palazzo F. The treatment challenge of hormone-refractory prostate cancer. Cancer Control. 2001;8:487-495.
6. Bianco FJ, Dotan ZA, Kattan MW, et al. Duration of response to androgen deprivation therapy and survival after subsequent biochemical relapse in men initially treated with radical prostatectomy [abstract]. J Clin Oncol. 2004;22(suppl): Abstract 4552.
7. Kantoff PW, Halabi S, Conaway M, et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study. J Clin Oncol. 1999;17:2506-2513.

*Associate Professor of Oncology and Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
 Associate Professor of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Address correspondence to: Michael Carducci, MD, CRB 1M88ÐOncology Urology, 1650 Orleans Street, Johns Hopkins University School of Medicine, Baltimore, MD 21231.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.