The changing pattern of management for hormone-refractory, metastatic prostate cancer

Abstract

Prostate cancer responds initially to hormonal manipulation by androgen withdrawal and peripheral androgen blockade. The inevitable progression to a hormone-refractory state is accompanied by an exacerbation of local symptoms and metastatic spread, principally to the bones, which has a considerable impact on quality of life and survival. Treatment of hormonerefractory prostate cancer is palliative, and surgery and radiotherapy are used for the relief of lower urinary tract symptoms and localized painful bony metastases. Systemic treatments are not widely accepted in this setting, but clinical trials have demonstrated the potential for bone targeting agents such as strontium-89 and the bisphosphonates to palliate painful bone metastases and to delay progression in certain settings. Chemotherapy with mitozantrone in combination with steroids has previously been shown to have palliative benefits and to delay progression. The additional costs incurred by the use of chemotherapy or bone-targeting therapies may be offset by gains in overall care with fewer in-patient admissions compared with steroid monotherapy . Recent clinical trials have demonstrated that docetaxel significantly improves patient quality of life, and importantly, increases survival. Future studies investigating the timing of chemotherapy, combinations with existing treatments or other novel therapies are underway.

Health-Related Quality of Life in Advanced Prostate Cancer and Its Treatments: Biochemical Failure and Metastatic Disease Populations

“…Bone pain in patients with prostate cancer indicates bone metastases and is one of the most common signs of metastatic disease progression or recurrence. 6 Consequently, the primary healthrelated quality of life (HRQL) impacts of metastatic prostate cancer are often attributed to bone metastases and resulting skeletal complications. 7 Commonly used measures of symptoms and HRQL in metastatic prostate cancer research are generic cancer HRQL instruments, including the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the Functional Assessment of Cancer TherapyeGeneral (FACT-G), which are often combined with the prostate cancerespecific module for the instrument, such as the EORTC QLQ-PR25 and the Functional Assessment of Cancer TherapyeProstate (FACT-P), respectively.…”

Strontium 89 Combined with Gemcitabine in Androgen-Resistant Prostate Cancer: Results of a Phase I-II Study

“…This finding presents an opportunity for bone-seeking targeted therapy, such as Sr89, a beta-emitting radionuclide that selectively localizes in bone mineral at sites of active osteogenesis [16]. Sr89 has a palliative effect in ARPC patients [1][2][3], however, it does not improve the overall survival whether it is given alone or in combination with other chemotherapeutic agents such as doxorubicin [6,17] or cisplatin [5,18]. In a phase II randomized study, Tu et al [6] reported that Sr89 given in combination with doxorubicin as a consolidation treatment (following 2 cycles of induction regimen consisting of ketoconazole, doxorubicin, estramustine and vinblastine) improved the survival of a subgroup of patients.…”

“…It emits beta particles that lead to a palliative effect (pain relief and reduction in pathologic fractures) in androgen-resistant prostate cancer (ARPC) [1][2][3]. Enhancement of this palliative effect by combination with chemotherapy was reported in several phase II studies [4][5][6].…”

“…It responds initially to hormonal manipulation by androgen withdrawal and peripheral androgen blockade. However, the inevitable progression to an androgen-resistant disease leads to a decreased quality of life and shortens survival [1,2].…”

Expression of osteoprotegerin from a replicating adenovirus inhibits the progression of prostate cancer bone metastases in a murine model

“…The growth of metastatic cells in bone disrupts normal bone physiology and structure (3) and causes a range of serious complications, including pain, pathological fractures and spinal cord compression (2, 4). Current treatments with surgery, radiotherapy, chemotherapy and bisphosphonate administration may slow disease progression, but are associated with deleterious side effects (5) and are often not curative. In light of the above, new therapies for this disease are urgently needed.…”