Optimizing the Use of Docetaxel in Men With Metastatic Prostate Cancer
Abstract and Introduction
In 2009, castration-resistant metastatic prostate cancer continues to account for more deaths in US men than any other cancer apart from lung cancer. Although novel targeted molecular, hormonal and immunologic agents are accelerating in their development in this disease, docetaxel and prednisone remain the standard palliative regimen for the majority of men who have progressed despite hormonal therapies. Thus, understanding the practical and often subtle issues of docetaxel initiation, duration of therapy, cessation of therapy and treatment holidays is critical for the informed use of this US Food and Drug Administration-approved regimen. In this review we address these topics in light of prognostic and predictive factors to help guide the rational use of docetaxel chemotherapy in men with this aggressive disease.
Prostate cancer is the most commonly diagnosed non-skin cancer in adult males in the USA. The American Cancer Society estimated that during 2009 about 192 280 new cases of prostate cancer would be diagnosed in the USA, along with 27 360 deaths from prostate cancer. In Europe, around 300 000 new cases of prostate cancer are diagnosed annually.
Metastatic prostate cancer is initially treated with androgen-deprivation therapy (ADT); although the disease initially responds well to ADT, progression occurs in the majority of patients, leading to castration-resistant prostate cancer (CRPC). Men with CRPC may experience symptomatic progression, resulting in weight loss, fatigue or pain from bone metastases, all of which can negatively impact quality of life (QoL). Two landmark trials (TAX 327 and Southwest Oncology Group (SWOG) 9916) showed superior survival and pain palliation with the use of docetaxel-based regimens compared with mitoxantrone/prednisone. Based on these findings, docetaxel combined with low-dose prednisone was approved by the US Food and Drug Administration for first-line chemotherapy in men with metastatic androgen-independent prostate cancer. Currently, no agent has been approved for second-line therapy following progression after docetaxel and prednisone, although a number of novel agents and other chemotherapeutics are under investigation.
The decision of when to initiate docetaxel-based chemotherapy is an important one that is not clearly addressed by existing treatment guidelines. A number of prognostic nomograms have been devised that assess multiple disease variables and aid in decisions about the timing and type of treatment to be given. However, it is widely acknowledged that there is a need for closer multidisciplinary collaboration between urologists, medical oncologists and radiation oncologists to optimize patient management.
This review addresses the factors that contribute to treatment decisions and offers guidance for the rational treatment of men with CRPC.