The Treatment Challenge of Hormone-Refractory Prostate Cancer

Julie A. Kish, MD, Raviender Bukkapatnam, MD, and Felipe Palazzo, MD


Cancer Control. 2001;8(6) 

In This Article

Abstract and Introduction


Background: Both the demographics and treatment of hormone-refractory prostate cancer (HRPC) are changing. Patients are younger and healthier, with fewer comorbidities. The "no treatment until symptoms" approach is disappearing. Chemotherapy is increasingly being utilized.
Methods: The authors review the steps involved in hormone management before chemotherapy is considered. The roles for chemotherapy in current clinical trials are examined.
Results: Effective hormonal management of the prostate cancer patient incorporates an understanding of the stages of hormone sensitivity and prescribing additional interventions beyond simple castration. Once hormone refractoriness is established, the combination of mitoxantrone and prednisone has become a standard chemotherapeutic approach. New agents such as docetaxel are being tested in phase III trials against mitoxantrone plus prednisone.
Conclusions: HRPC is now regarded as a chemotherapy-sensitive tumor. The goals of chemotherapy in HRPC are to decrease PSA level and improve quality of life. New agents and combinations are needed to improve survival.


The treatment of hormone-refractory prostate cancer (HRPC) is both challenging and rewarding as new targets are elucidated. As the most common malignancy in men the United States and the second leading cause of cancer death, the large number of patients requiring posthormonal therapy is increasing. In the past, only patients with proven metastatic disease or those with post-local therapy failures received hormonal treatment. Due to the demographic changes in patients treated with hormonal therapy, those now receiving hormonal therapy include not only the patients previously mentioned, but also patients with biochemical failures, those on intermittent therapy, those at high risk for recurrence (T3-4, Gleason score [infinity][infinity][infinity] PSA >20), and patients with locally advanced dis-ease treated with radiation. Thus, the extent of disease at the time of hormonal therapy initiation and ultimate hormone refractoriness may vary considerably. This stage migration may influence treatment outcome.

Despite initial success with hormonal therapy, the durability of this response (median duration <2 years) is inadequate, and subsequent treatment is needed for these patients. With recent advances in the under-standing of HRPC, newer treatment targets are being identified. In the past, all treatments including chemotherapy were considered inactive, but newer chemotherapy drugs and drug combinations are now demonstrating improved response rates. [1] The use of PSA as an effective marker of clinical success in the absence of measurable disease has been a boon to the evaluation of therapies. This article outlines an approach to HRPC and examines current trends in chemotherapy and newer targets.


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