Prostate cancer metastatic

Saad F, Gleason D, Murray R,Venner P,Tchekmedyian NS, Lacombe L, Chin J,Vinholes J, Goas JA, Chen B-L, et al. Zoledronic acid is well tolerated for up to 24 months and significantly reduces skeletal complications in patients with advanced prostate cancer metastatic to bone. J Urol 2003 169(suppl) 394. Abstract 1472. 

Prosta.te Ca.ncer, Estrogen has an inhibitory effect on the prostate in addition to its suppression of gonadotropin secretion by the pituitary. The three- and five-year survival rates in prostate cancer patients with metastatic disease improved when treated with DES (7) alone or along with castration. However, DES does not improve the survival rates in patients whose carcinoma is confined to the prostate. Small doses of DES (1 mg/d) appear to retard prostate cancer growth and could reduce the cardiovascular complications associated with larger doses (5 mg/d) (135) (see... 

Contrast the benefits and risks of luteinizing hormone-releasing hormone (LHRH) singleagent therapy and combined androgen blockade in the first-line therapy of metastatic prostate cancer. 

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

CC is a 69-year-old man who presents with metastatic prostate cancer. His disease is metastatic to the bones, and his primary symptom is bone pain. 

TABLE 89-7. First-Line Chemotherapy Regimens for Metastatic Hormone-Independent 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). 

Another focus has been on the invasiveness of prostate cancer cells since prostate cancer lethality is tied to metastatic processes. Metastatic cells have acquired the ability to invade basement... 

Forbes, K, K Gillette, and I Sehgal. 2003. Lycopene increases urokinase receptor and fails to inhibit growth or connexin expression in a metastatically passaged prostate cancer cell line a brief communication. Exp Biol Med 228 967-971. 

Paule, B, S Terry, L Kheuang, P Soyeux, F Vacherot, and A de la Taille. 2007. The NF-kappa B/IL-6 pathway in metastatic androgen-independent prostate cancer new therapeutic approaches. World J Urol 25 477 189. 

Ryan, CJ, CM Haqq, J Simko et al. 2007. Expression of insulin-like growth factor-1 receptor in local and metastatic prostate cancer. Urol Oncol 2007(2) 134—140. 

Until definitive trials are published, it is appropriate to use either LHRH agonist monotherapy or combined androgen blockade as initial therapy for metastatic prostate cancer. 

Docetaxel, 75 mg/m2 every 3 weeks, combined with prednisone, 5 mg twice daily, has been shown to prolong survival in hormone-refractory metastatic prostate cancer. The most common adverse events were nausea, alopecia, and myelosuppression. Docetaxel can also cause fluid retention and peripheral neuropathy. 

The combination of estramustine 280 mg by mouth three times daily on days 1 to 5 and docetaxel 60 mg/m2 on day 2 of a 21-day cycle also improves survival in hormone-refractory metastatic prostate cancer. Estramustine causes a decrease in testosterone and a corresponding increase in estrogen, which results in an increase in thromboembolic events, gynecomastia, and decreased libido. 

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]. 

Prostatic cancer In clinical trials involving 350 patients with metastatic prostatic cancer, 11 deaths were reported within 2 weeks of starting high-dose ketoconazole (1200 mg/day). It is not known whether death was related to therapy. High ketoconazole doses are known to suppress adrenal corticosteroid secretion. Hypersensitivity reactions Anaphylaxis occurs rarely after the first dose. Hypersensitivity reactions, including urticaria, have been reported. 

Breast, ovarian, cervical, bladder and prostate cancer gastrointestinal adenocarcinomas Metastatic pancreatic cancer small cell lung cancer Leukemia Breast cancer... 

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. 

In another study by the same group, [ F]-fluoride-PET/CT was compared with [ F]-fluoride-PET, bone scintigraphy and SPECT in 44 patients with high-risk prostate cancer [195]. For detection of skeletal metastatic spread [ F]-fluoride-PET/CT revealed to be significantly more sensitive and specific than bone scintigraphy (p < 0.05) and SPECT (p < 0.05), and significantly more specific than [i F]-fluoride-PET (p < 0.001). 

Varambally S, Yu J, Laxman B, et al. (2005) Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell% 393 06. 

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. 

---