Chemotherapy for advanced prostate cancer
INTRODUCTION Prostate cancer will result in approximately 30,000 annual deaths in men in the United States in 2005 and is the second leading cause of cancer deaths in men after lung cancer.1,2 While the death rate from prostate cancer has been declining due to a number of factors such as earlier diagnosis and effective, less morbid local treatment options, approximately 6% of men will present with distant metastases and approximately 40% to 60% will relapse following local treatments.2-4 In general, androgen suppression leads to the response and stabilization of metastatic hormone-sensitive disease for approximately 18 to 24 months with a historic median survival from the time of diagnosis of metastases ranging from 24 to 30 months.5,6 A recent update of select patients from the Pound database from Johns Hopkins has demonstrated a median survival from development of metastases to death of 6.5 years.7 Prostate-specific antigen (PSA) doubling time at relapse following radical prostatectomy, time to recurrence, and original Gleason score were predictive of metastasis-free survival, illustrating the heterogeneity of this disease.7 However, eventually these patients will develop progressive hormone-refractory metastatic prostate cancer and these patients have a median survival of approximately 12 to 18 months.8-11 The concept that hormone-refractory metastatic prostate cancer is a chemo-resistant disease has been challenged by recent clinical trials. The use of surrogate outcomes such as PSA response has led to the more rapid identification of novel agents with activity in hormonerefractory metastatic prostate cancer (HRPC). Docetaxel (Taxotere), a taxoid with a more manageable benefit-totoxicity ratio than historic cytotoxic agents used in prostate cancer, has demonstrated a clinical benefit and overall survival advantage in recent multi-institutional trials. Further refinements of the definitions of hormone independence, quality-of-life outcomes, and surrogate markers of response have led to improved standardization across clinical trials that allow for head to head comparisons of active agents.12,13 The earlier detection of biochemical recurrence and asymptomatic metastatic disease with the use of serum PSA measurements and improved imaging techniques may also translate into the earlier initiation of therapy before disease burden and pain become overwhelming factors. While hormone-refractory metastatic prostate cancer remains an incurable disease, chemotherapy has come to play a role in prolonging patient survival with meaningful quality-of-life endpoints and has generated optimism about progress among both clinicians and patients.