Prostate cancer immunotherapy moves forward

Brendan Curti, M.D.
Director, Genitourinary Oncology Research
Director, Immunotherapy Clinical Program
Medical oncologist, Providence Oncology and Hematology Care Clinic-Eastside

Published August 2012

Prostate cancer is a common disease in the United States, with more than 241,000 new diagnoses and 28,000 deaths projected for 2012 alone. In its early stage the disease can be cured with surgery or radiation. For some carefully selected patients whose prostate cancer is indolent, surveillance is the best approach.

There are many approved treatments for men with metastatic disease, most of which work by blocking androgen (testosterone) production. Despite high initial rates of cancer regression with androgen blockade, these treatments are not a cure; the median duration of response is about 18 months. Most men with metastatic disease develop androgen-independent prostate cancer, or AIPC, and die as a result.

There are a number of new research approaches available at Providence Cancer Center that may help men with AIPC. These studies combine immunotherapy with other agents to stimulate an immune response that can control the cancer.

Sipuleucel immunotherapy, also known as Provenge, has been approved by the U.S. Food and Drug Administration to treat minimally symptomatic metastatic AIPC. Sipuleucel is prepared from antigen- presenting cells harvested from the patient. These cells are stimulated ex vivo with a synthetic protein that can enhance immunity against prostate cancer.

The FDA approved sipuleucel because it can prolong survival, but the drug does not generally lower PSA, which is the most common measurement of disease burden in men with metastatic disease. This clinical trial combines sipuleucel with abiraterone. Abiraterone inhibits testosterone production within prostate cancer cells and is approved for the treatment of AIPC after disease progression on chemotherapy.

The idea behind the study is that abiraterone will cause the death of prostate cancer cells, which will release antigen (target proteins for immune response). Sipuleucel will amplify the immune response, potentially resulting in longer control of the cancer and improved survival.

The target population for this study is men with AIPC and metastatic disease to bone or lymph nodes, but who have not had prior chemotherapy and who do not have significant pain or other symptoms from cancer. Two schedules are being tested: concurrent sipuleucel and abiraterone versus sipuleucel followed by abiraterone starting six weeks later. Patients will be followed for response, survival and analysis of immunological response.

A new class of antibodies

Another way to stimulate immune responses to cancer is to increase the activity of tumor-specific T cells. In the past few years, a new class of antibodies has been developed that influences the control mechanisms of the T cells, and these antibodies are showing great therapeutic potential.

The four main control pathways for T cells are CTLA-4, PD-1, 4-1BB and OX40. Providence Cancer Center is the only research center testing therapies to influence all four of these pathways. In prostate cancer, we are testing an antibody to OX40 given in conjunction with a single dose of cyclophosphamide chemotherapy and radiation.

This treatment combination was based on preclinical research performed by Andrew Weinberg, Ph.D., and Marka Crittenden, M.D., Ph.D. Based on these preclinical experiments, OX40 can greatly amplify the response to tumor antigen released by chemotherapy and radiation. This approach enhanced the regression of cancers in animal models.

This clinical trial is being offered to men with AIPC that has failed prior therapy, which can include chemotherapy. Patients must have at least one bone metastatic deposit suitable for radiation. The main goals for the study are to assess the safety, PSA and radiographic responses, and to perform sophisticated analysis of the immune response to this combination. 

To refer a patient or learn more about these or other trials, contact research coordinator Scot Lary, RN, at 503-215-2604.

Clinical articles by Brendan Curti, M.D.