Considerations for Integrating Chemotherapy

In 2004, docetaxel (Taxotere^®) was approved for the treatment of castration-resistant prostate cancer (CRPC). In 2010, the Food and Drug Administration (FDA) approved 2 new prostate cancer drugs, cabazitaxel (Jevtana^®) and sipuleucel-T (Provenge^®). The new, diverse antitumor agents, as well as new cancer vaccines and radiotherapies being developed, raise the question of how medicine will integrate these emerging treatments, according to Daniel P. Petrylak, MD, cochair of the 2011 Interdisciplinary Prostate Cancer Congress (IPCC).

Petrylak, director of the Prostate Cancer Program and Professor of Medicine at New York-Presbyterian Hospital/Columbia University Medical Center (NYPH/CUMC), spoke about how to integrate systemic chemotherapy options into advanced prostate cancer disease management. He said that the traditional, linear regimen of prostate cancer treatment may need to be reexamined as oncologists learn new ways to incorporate new therapies, including those that target angiogenesis, bone-targeted agents, and agents that target oncoproteins such as the Src oncogene or clusterin.

Combining these agents with chemotherapy in an optimal sequence presents a big challenge, both in practice and in the design of clinical trials, according to Petrylak, who posed these questions:

1. What is the optimal sequence of these drugs?

2. When is a patient truly castration resistant? When is the patient going to stop responding to antihormonal therapies?

3. How do we optimize these treatments without markers to tell us the optimal times to administer them?

Another consideration, according to Petrylak, involves immunotherapies, which pose special challenges because they cause prolonged activation of the immune system, and this response may interact with the subsequent treatments the patient receives. He said that researchers will now need to consider extended survival endpoints, which have more than doubled in some cases, increasing the time it takes to complete clinical trials. Investigators will need to look at surrogate endpoints to make trial design more rapid and efficient.

Petrylak said he believes that effective combination therapies cannot be adequately determined until researchers molecularly phenotype individual types of prostate cancer. We need different types of markers to tell us what treatments are appropriate, he suggested.

While the standard of care for CRPC is docetaxel/prednisone, phase 3 studies combining docetaxel with novel targeted agents and new biological approaches may redefine the scheme for advanced stage prostate cancer, according to Petrylak, who added that much evidence-based research needs to be done.