Editorial

E. David Crawford, MD

As we digest the recent findings in prostate cancer research from our International Prostate Cancer meeting and the 2007 ASCO Prostate Cancer symposium I am pleased that this issue of Grand Rounds in Urology expands upon the current treatment options being evaluated for hormone-refractory prostate cancer (HRPC). While docetaxel is the only FDA-approved first-line therapy for HRPC and there is no approved second-line treatment, the two articles in this issue address the impending availability of new treatment options, likely within the next several months.

Dr. Nancy Dawson is an international expert in prostate cancer and discusses the current state of prostate cancer research, including immunotherapy, gene therapy, bone-targeted therapies, vitamin D analogs, and novel cytotoxic agents. She gives an extremely thorough overview of the ongoing research and covers how the plethora of newer treatment options, including sipuleucel-T, ixabepilone, satraplatin, denosumab, and DN-101, will be used in combination with already established effective hormonal and chemotherapy drugs to address gaps in treatment, particularly for patients progressing on androgen deprivation therapy in the absence of metastatic disease and for taxane-refractory patients. Dr. Dawson evaluates a number of recently published and ongoing clinical trials, and she concludes that the significant progression-free and overall survival benefits being reported should create abundant enthusiasm among those of us who have been awaiting new treatment options for our patients.

In the second article Dr. Daniel Petrylak focuses on two particular treatment options, DN-101 and satraplatin, from which recent findings have elevated the levels of anticipation among practicing physicians, and likely, patients. Dr. Petrylak initially discusses the ASCENT trial, a randomized phase II trial that compared pulsed highdose calcitriol, 45 μg daily (DN101), plus 36 mg/m2 per week docetaxel for 3 out of 4 weeks versus docetaxel alone. While no significant difference in 50% PSA decline at 6 months (the primary endpoint of this study) or overall PSA decline time to PSA response or objective response rate were noted between the weekly docetaxel and the arm combining docetaxel with DN101, he notes that two observations made this regimen worthy of further study. Since prospective confirmation is needed to determine if using DN101 is a novel way of reducing docetaxel-based toxicity, as well as improving survival, the ASCENT II trial was opened in January 2006. Dr. Petrylak further discusses another novel therapy option, the oral platinum satraplatin. Dr. Petrylak describes the results of the phase III SPARC trial. He reports that satraplatin prolongs progression- free survival in hormone-refractory patients who have failed either docetaxel or non-docetaxel containing chemotherapy regimens. Progression-free survival was a composite of several endpoints, which was measured by increased pain. Increased pain was measured by a number of factors including RECIST. Dr. Petrylak describes how the SPARC data seem to show that this compound’s benefit comes from an ability to prevent the recurrence of pain. While more data will be presented in June at the annual meeting of ASCO, based on these data, a new drug application was filed with the FDA in February 2007. He concludes that these two novel agents, DN101 and satraplatin, have promising activity in first-line and second-line hormone- refractory prostate cancer, respectively. These and other trials have raised the excitement level in prostate cancer and offer the opportunity to integrate these therapies even early in the disease. This is what happened years ago in breast and colorectal cancers.

Sincerely,

E. David Crawford, MD
Medical Editor
Grand Rounds in Urology

CONTENTS

• Continuing Medical Education
 

• Future Treatment Options in Advanced Prostate Cancer: A Status Report
  Nancy A. Dawson, MD

• New Developments in Chemotherapy for Hormone Resistant Prostate Cancer
  Daniel P. Petrylak, MD

 
• Instructions for Authors

 

• Urology Links
 

• Post-Test

• Application for CME Credit

• Directory of Meetings

Download a PDF of the full issue