Prostate metastatic, treatment

Profound hypocalcemia occurred in a patient with osteoblastic metastatic carcinoma of the prostate after treatment with diethylstilbestrol 15 mg/day for 7 days (SED-12,1032) (4). 

Understand the role of chemotherapy in the treatment of metastatic prostate cancer. ... 

Ultrasensitive assays for PSA contribute to the earlier detection of prostate cancer relapse and (or) residual disease in prostatectomized patients as well as the more timely evaluation of response to current therapies. PSA determinations can be useful in detecting metastatic or persistent disease in patients following surgical or medical treatment of prostate cancer. Persistent elevation of PSA following treatment, or an increase in the pretreatment PSA concentrations, is indicative of recurrent or residual disease. Hence, PSA is widely accepted as an aid in the management of prostate cancer patients, and serum levels are most useful when sequential values are obtained and monitored over time. After complete removal of the prostate gland (radical prostatectomy), PSA levels should become very low or undetectable. A rise of the serum PSA level in prostatectomy patients indicates residual prostate tissue, recurrence, or metastasis of the disease (13, 16, 24, 36). 

Metastatic bone disease (MBD) is characterized by very high levels of bone turnover in regions proximal to the tumour [33]. Bone resorption inhibitors such as bisphosphonates represent the current standard of care for the treatment of bone metastases primarily due to breast or prostate cancer and multiple myeloma. It has been proposed that other strong anti-resorptives such as a Cat K inhibitor could be useful in the treatment of bone metastases. Evidence for this has been presented in the form of a preclinical MBD model in which human breast cancer cells are implanted into nude mice. Treatment with a Cat K inhibitor gave a significantly lower area of breast cancer-mediated osteolytic lesions in the tibia [34]. In a separate study, the efficacy of a Cat K inhibitor in the reduction in tumour-induced osteolysis was found to be enhanced in the presence of the bisphosphonate zolendronic acid [35,36]. When prostate cancer cells were injected into the tibia of SCID mice, treatment with a Cat K inhibitor both prevented and diminished the progression of cancer growth in bone [37]. 

Such a medical adrenalectomy is an efficacious treatment for metastatic breast and prostate cancer, since it diminishes the levels of circulating sex hormones. Glucocorticoids are administered concomitantly to suppress enhanced corticotrophin release. Cortisol is preferable to dexamethasone in this situation because aminoglutethimide markedly enhances the hepatic microsomal metabolism of dexamethasone. Hepatic enzyme induction may be responsible for the development of tolerance to the side effects of aminoglutethimide, such as ataxia, lethargy, dizziness, and rashes. 

Other clinical uses of estrogens and progestins include the treatment of dysfunctional uterine bleeding, dysmenorrhea, endometriosis, and rarely, metastatic prostate cancer. 

Antiandrogens such as cyproterone acetate (5.54) or the nonsteroidal flutamide (5.55, a substituted anilide) are competitive antagonists on the cytosol receptor. They do not prevent DHT formation rather, they inhibit the nuclear retention of DHT in the prostate. They cause feminization in male fetuses and decrease libido in males. Cyproterone is also an active progestogen. In men, antiandrogens are used commonly in the treatment of prostatic cancer and uncommonly to inhibit sex drive in hypersexuality in women, antiandrogens are used to treat virilization. Bicalutamide (5.56) and nilutamide (5.57) are potent, orally active antiandrogens that may be used in the treatment of metastatic prostate carcinoma. 

In a phase II study of androgen suppression therapy for prostate cancer, 95 patients with recurrent or metastatic prostate cancer received cyclical 8-month periods of treatment with leuprolide acetate and nilutamide, with... 

Schroder FH, Whelan P, De Reijke TM, Kurth KH, Pavone-Macaluso M, Mattelaer J, Van Velthoven RF, Debois M, Collette L. Metastatic prostate cancer treated by flutamide versus cyproterone acetate final analysis of the European Organization for Research and Treatment of Cancer (EORTC) protocol 30892. Eur Urol 2004 45 457-64. 

Carcinoma. Estrogen has been used to treat metastatic breast cancer in men and postmenopausal women. Advanced prostate cancer in men may also respond to estrogen treatment. Progesterone is helpful in treating uterine cancer and several other types of metastases, such as breast, renal, and endometrial carcinoma. 

However, several types of cancer do not respond well to treatment. For example, the majority of metastatic cancers cannot be cured by current chemotherapeutic methods or by any other type of treatment.11 In addition, some of the most common forms of adult neoplastic disease are difficult to treat by using anticancer drugs. As indicated in Table 36-9, the number of deaths associated with colorectal, prostate, and breast cancer is unacceptably high, and the mortality rate for lung cancer and pancreatic cancer is well over 90 percent in both men and women. 

Plotnikov, A., Niego, B., Ophir, R., Korenstein, R. and Keisari, Y. (2006) Effective treatment of mouse metastatic prostate cancer by low electric field enhanced chemotherapy. Prostate 66, 1620-1630. 

Prostatic cancer is androgen-dependent and metastatic disease can be helped by orchidectomy, or by a gonadorelin analogue, e.g. buserelin, goserelin, leuprorelin or triptorelin. These cause a transient stimulation of luteinising hormone and thus testosterone release, before inhibition occurs some patients may experience exacerbation of tumour effects, e.g. bone pain, spinal cord compression. Where this can be anticipated, prior orchidectomy or antiandrogen treatment, e.g. with cyproterone or flutamide, is protective. 

Hussain M, Fisher El, Petrylak DP, O Connor J, Wood DP, Small EJ, Eisenberger MA, Crawford ED. Androgen deprivation and four courses of fixed-schedule suramin treatment in patients with newly diagnosed metastatic prostate cancer a Southwest Oncology Group Study. J CUn Oncol 2000 18(5) 1043-9. 

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