Non-hormonal systemic therapy in men with hormone-refractory prostate cancer and metastases: a systematic review from the Cancer Care Ontario Program in Evidence-based Care's Genitourinary Cancer Disease Site Group

Abstract

Background: Prostate cancer that has recurred after local therapy or disseminated distantly is usually treated with androgen deprivation therapy; however, most men will eventually experience disease progression within 12 to 20 months. New data emerging from randomized controlled trials (RCTs) of chemotherapy provided the impetus for a systematic review addressing the following question: which non-hormonal systemic therapies are most beneficial for the treatment of men with hormone-refractory prostate cancer (HRPC) and clinical evidence of metastases?

Current Management of Castrate-Resistant Prostate Cancer

“…Based on the results of those two trials, it is now recommended that, for men with clinical or biochemical evidence of progression and evidence of metastases, treatment with docetaxel 75 mg/m 2 administered intravenously every 3 weeks with 5 mg oral prednisone twice daily should be offered to improve overall survival, disease control, symptom palliation, and quality of life 16 .…”

“…Men with hrpc should receive treatment to optimize symptom control. Use of estramustine in combination with other cytotoxic agents is not recommended because of the increased risk of clinically important toxicities without evidence of improved survival or palliation 16 .…”

Frequent Gene Products and Molecular Pathways Altered in Prostate Cancer- and Metastasis-Initiating Cells and Their Progenies and Novel Promising Multitargeted Therapies

“…Prostate cancer (PC) is among the most commonly diagnosed malignancies and is the second leading cause of cancerrelated deaths in men (1)(2)(3)(4)(5)(6). Although progress in developing early detection tests has led to improved clinical treatments of patients diagnosed with lowgrade and organ-confined PCs by radical prostatectomy and radiotherapy, the progression to locally advanced, invasive and metastatic castration-resistant prostate cancers (CRPCs) usually leads to disease relapse (1,2,5,(7)(8)(9).…”

“…Although progress in developing early detection tests has led to improved clinical treatments of patients diagnosed with lowgrade and organ-confined PCs by radical prostatectomy and radiotherapy, the progression to locally advanced, invasive and metastatic castration-resistant prostate cancers (CRPCs) usually leads to disease relapse (1,2,5,(7)(8)(9). In fact, despite the fact that the patients with locally advanced PCs initially respond to androgen deprivation by surgical or chemical castration, androgen-independent (AI) lesions may eventually develop and progress despite low levels of circulating androgens (9)(10)(11).…”

“…The CRPCs are refractory to conventional treatments by antihormonal therapy, radiotherapy and chemotherapy (1)(2)(3)(4)(5)(7)(8)(9)12). More specifically, the first-line systemic docetaxelbased chemotherapies used as care for the patients with high-risk or metastatic CRPCs are only palliative and typically culminate in the death of patients after about 12-19 months (1)(2)(3)5,8,13).…”