Chemotherapy for Advanced Prostate Cancer
The primary modality of treatment for patients with disseminated cancer of the prostate fo-cusses on the suppression of androgenic stimulation of tumour growth. Androgen deprivation procedures of various kinds result in subjective/objective clinical benefits in the majority (70–80%) of patients with metastatic disease and, clearly, reflect some of the most effective systemic palliative treatments for solid tumours in man. Paradoxically however, the development of endocrine resistance, which is observed within a relatively predictable time frame, is an extraordinarily effective phenomenon. In prostate cancer, contrary to breast cancer, responses to second-line endocrine manipulations are uncommon, usually brief and subjective and, more important, have no impact on survival. Extensive data accumulated over the past few decades, derived from large-scale, prospective randomised trials testing various methods of androgen deprivation, have shown that the median time to progression and the median survival in cohorts of patients have consistently ranged from 12–18 months and 24–30 months, respectively [1,2]. These data also stress that the development of effective non-hormonal cytotoxic approaches is the key step in order to accomplish significant advances in the systemic treatment of this disease. Preclinical data have shown that various phenotypic changes are increasingly expressed in parallel with the development of endocrine resistance . These may represent either somatic mutations from a hor-monally sensitive to an insensitive state, expansion of previously insensitive cell clones, or, most likely, both .
KeywordsTestosterone Flare Methotrexate Melphalan Cyclophosphamide
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