New Guideline Emphasizes Sequenced Therapy for Castration-Resistant Prostate Cancer

Charles Bankhead

June 2013, Vol 4, No 5 - Prostate Cancer

San Diego, CA—Evidence-based drug sequencing should form the basis of treatment for castration-resistant prostate cancer (CRPC), according to a new guideline from the American Urolo­gical Association (AUA) released at the 2013 AUA annual meeting.

Organized into strategies for 6 types of patients with CRPC (“index patients”), the guideline emphasizes thera­pies that have demonstrated efficacy in the specific index patient.

Over the past 3 years, 4 new therapies for CRPC have received US Food and Drug Administration approval. Other drugs in development have shown promise and could eventually lead to even more options for a disease that once had virtually no effective treatment options. In part, the AUA guideline is a response to the rapid development of treatments for CRPC, according to Michael S. Cookson, MD, Professor of Urologic Surgery, Vanderbilt University, Nashville, TN, who chaired the guideline panel.

“We wanted to offer physicians guidance in navigating the maze of treatment options that have become available in fairly rapid succession,” said Dr Cookson. “The guideline is based on the strongest and most current information available; yet, we think physicians will find it easy to understand and use.”

The 6 Index Patients, by Disease Status
The 6 types of index patients that form the basis of the guideline represent the key conditions that define different stages of CRPC. Those situations include:

  • Presence or absence of metastases
  • Presence or absence of symptoms and severity of symptoms
  • Performance status
  • History of exposure to docetaxel (Taxotere).

Index Patient 1 has no symptoms or metastases. Observation is an option, and antiandrogens or androgen-synthesis inhibitors may be offered to men who refuse observation. Chemothera­py or immunotherapy should not be used, except in a clinical trial setting.

Index Patient 2 has metastatic CRPC, but no symptoms or only mild symptoms, and has not been treated with docetaxel. Abiraterone (Zytiga) plus prednisone, docetaxel, or sipuleucel-T (Provenge) are options for patients with good performance status. First-generation antiandrogens, ketoconazole-plus-steroid combinations, and observation are other options for such patients, particularly patients who cannot use or who do not want to use standard therapies.

Index Patient 3 has symptomatic metastatic CRPC, good performance status, and no previous exposure to chemotherapy. Patients with good performance status should be offered docetaxel, according to the guideline. Physicians may offer the combination of abiraterone and prednisone. For selected patients who do not want or who cannot use standard therapy, physicians may offer ketoconazole plus a steroid, mitoxantrone (Novan­trone), or radionuclide therapy. Patients in this category should not be offered estramustine (Emcyt) or sipuleucel-T.

Index Patient 4 is defined by the presence of symptoms, metastases, and poor performance status, and no previous exposure to docetaxel therapy. These patients may be offered abir­aterone plus prednisone, or alternatively, ketoconazole plus a steroid or radionuclide therapy when they are unable or are unwilling to use abir­aterone. If a patient’s performance status is directly related to the disease, physicians may offer docetaxel or mitoxantrone. This type of patient should not be offered sipuleucel-T.

Index Patient 5 is symptomatic, has good performance status, and has been treated previously with docetaxel. These patients should be offered abir­aterone plus prednisone, cabazitaxel (Jevtana), or enzalutamide (Xtandi). If those drugs are unavailable, physicians may offer ketoconazole plus a steroid. Retreatment with docetaxel also may be offered to patients who were benefiting from treatment but who discontinued because of reversible side effects.
Index Patient 6 is symptomatic, has poor performance status, and has been treated with docetaxel. Palliative care should be offered to patients in this category. Selected patients may be offered abiraterone plus prednisone, enz­alutamide, ketoconazole plus a steroid, or radionuclide therapy. The patients should not be offered systemic chemotherapy or immunotherapy.

Bone Health
The guideline also addresses bone health in patients with metastatic CRPC. Physicians should offer treatment aimed at preventing fractures and skeletal-related events. Either den­osumab (Xgeva) or zoledronic acid (Zometa) is an option for preserving bone health in this population.