Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We treated 16 patients who had hormone refractory metastatic prostate cancer with 400 mg. ketoconazole orally every 8 hours. None of the patients had an objective response, although 6 (37.5 per cent) had stable disease (2 of whom had a subjective decrease in bone pain). The median duration of stable disease was 6.8 months (range 2 to 12 months) and side effects were seen in 14 patients. Nausea, vomiting or anorexia was noted in 10 patients, rash and pruritus in 2, transient abnormal liver function tests in 1 and transient pulmonary infiltrates in 1. Nine prior studies investigating the use of ketoconazole in hormone refractory metastatic prostate cancer were reviewed. Only 1 complete response was reported. A partial response was noted in 14 per cent of the patients. Most of the patients had stable or progressive disease. High dose ketoconazole as a single agent appears to have limited use in patients who have failed prior systemic therapy.
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PMID:High dose ketoconazole for the treatment of hormone refractory metastatic prostate carcinoma: 16 cases and review of the literature. 265 29

Pancytopenia, rash, and fever developed in a 66-year-old man being treated for metastatic prostate cancer with diethylstilbestrol (DES). Only the withdrawal of DES resulted in the prompt resolution of symptoms, signs, and laboratory manifestations. Both immunologic and endocrinologic mechanisms are implicated and must be considered by physicians using DES for the palliative management of prostate cancer.
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PMID:Pancytopenia, rash and fever caused by diethylstilbestrol used for prostate cancer. 272 59

The effectiveness of aminoglutethimide as an adrenal inhibitor has been well-documented by decreases in plasma testosterone and delta 4 levels, which fall significantly following the drug in previously orchiectomized patients. The use of cortisone or cortisol along with aminoglutethimide complicates the interpretation of the role of aminoglutethimide in effecting clinical responses. However, since physiologic replacement doses were used in most cases, a significant role for cortisone in effecting a clinical response is unlikely. Aminoglutethimide does have side-effects including rash and lethargy. It requires administration of replacement doses of cortisone and sometimes mineralocorticoid as well since it inhibits adrenal steroid synthesis in all pathways. Peripheral adrenal androgen inhibitors, such as flutamide, Megace, cyproterone acetate or 5 alpha-reductase inhibitors, in the future may be equally effective and simpler to administer than aminoglutethimide but objective and adequate numbers of studies using acceptable objective criteria must be done in order to adequately compare these drugs to aminoglutethimide. There appears to be approximately a 33% response rate (partial objective regression and objectively stable) following blockade of adrenal androgens in patients in relapse after castration. Blockade of adrenal androgen is certainly more tolerable and has many fewer side-effects than the alternative of chemotherapy which does not give response rates in most cases that are significantly different from those noted with aminoglutethimide. Murray's paper, combined with prior studies by Drago et al., goes a long way in establishing adrenal androgen blockade with that drug as the next step to be taken in patients following relapse from prior castration (medical or surgical). The most important question revolves around the timing of adrenal androgen blockade. As stated by Murray, will adrenal androgen blockade provide better survival if given earlier following relapse? The answer is not known yet. The answer may come from the work of Labrie [1], Geller and Albert [2] and others, who suggest that total survival in prostate cancer may be improved with blockade of adrenal androgens not after relapse following castration, but with panandrogen blockade at the time of initial therapy for prostate cancer.
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PMID:Adrenal androgen blockade in relapsed prostate cancer. 293 57

Aminoglutethimide (AG) and hydrocortisone (HC) were given to 20 patients with advanced prostatic cancer resistant to conventional hormonal therapy. Most patients had painful bone metastases and were heavily pretreated. 12 of 16 patients required narcotic analgetics. 8 of 20 were bedridden. AG + HC produced relief of bone pain in 12 patients (75%) and only 4 required narcotics after treatment. The performance status improved in 8 of 20 patients (40%). However, the number of bone metastases seen in bone scans decreased in only 4 patients (22%). The level of serum alkaline phosphatase decreased in 11 of 18 patients and that of acid phosphatase in 8 of 16 patients. The reduction of bone pain lasted approximately 4 months (range 1-15 months). The median lifespan between the start of AG treatment and death was 8 months (range 2-22 months). There was no difference in survival between responders and nonresponders. 3 patients had skin rash, 1 lethargy and 1 thrombocytopenia.
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PMID:Aminoglutethimide for advanced prostatic cancer resistant to conventional hormonal therapy. 336 30

We describe an unusual case of morbilliform skin eruption caused by diethylstilbestrol in a patient with stage D prostatic cancer. A widespread erythematous maculopapular rash and urticaria appeared with repeated challenges of diethylstilbestrol and resolved with drug withdrawal. In addition, the literature on various types of dermatitis medicamentosa in male patients with prostatic cancer treated with diethylstilbestrol is reviewed.
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PMID:Morbilliform skin eruption owing to diethylstilbestrol. 623 85

Some of the most promising systems for the controlled release of bioactive agents, i.e., peptides or hormones, involve the encapsulation or entrapment of hormones or peptides in biocompatible polymeric devices that enable their continuous release over prolonged periods. In urology, two major pathologic conditions, androgen deficiency and prostate cancer, currently benefit from treatments based on controlled delivery. Leuprolide acetate depot (Lupron-depot) was one of the first controlled-delivery systems used for the treatment of prostate cancer. Clinical studies indicate that patients with prostate cancer who undergo therapy with leuprolide acetate depot can benefit from this treatment. Currently available androgen-replacement therapies include the oral administration of testosterone tablets or capsules, depot injections, sublingual treatment, and skin patches. However, side effects such as metabolic inactivation of testosterone on oral administration; fluctuations in levels of the hormone; and burning, rash, and skin necrosis during the use of skin patches may occur. These side effects may be avoided through the application of encapsulated Leydig cells, which produce testosterone. Studies in our laboratory have shown that Leydig cells encapsulated in alginate/poly-L-lysine/alginate microspheres are capable of secreting testosterone in culture and in vivo. Microencapsulated Leydig cells delivered intraperitoneally into castrated rats maintained a testosterone level of 0.51 ng/ml for more than 3 months without any human chorionic gonadotropin stimulation. Similar studies are also being conducted in our laboratory on encapsulation of ovarian cells for the secretion of progesterone and estrogen in culture and in vivo using microencapsulation techniques.
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PMID:Controlled release of therapeutic agents: slow delivery and cell encapsulation. 1076 49

The breakthrough discovery of the anti-angiogenic effects of thalidomide gave impetus to a series of clinical trials in patients with solid tumors and hematologic malignancies. Thalidomide has been shown to block the activity of angiogenic substances like bFGF, VEGF and interleukin 6. This drug also down-regulates TNF alpha. Thalidomide has shown clinical antitumor activity in single-agent, phase II clinical trials in AIDS-related Kaposi sarcoma, glioma, multiple myeloma refractory to chemotherapy, and hormone-refractory prostate cancer. In contrast, thalidomide was inactive in breast, lung and kidney cancer. The dose-limiting toxicity of thalidomide is sedation. Other adverse effects include skin rash, constipation, dry mouth and liver function abnormalities, along with peripheral neuropathy and the drug's well-known teratogenic potential. The advantages of thalidomide include the convenience of the oral route of administration, the drug's toxicity profile--substantially milder than that of chemotherapy--and its low cost. The potential role of thalidomide in the treatment of human neoplasia will be confirmed by means of randomized clinical trials.
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PMID:[Thalidomide. Clinical trials in cancer]. 1118 34

Suramin, a polysulphonated napthylurea, has been extensively evaluated over the past 10 years as an anticancer agent, with the most interest in the treatment of prostate cancer. Early clinical results were promising with response rates of up to 70% being reported. However, a recent double-blind study showed only modest palliative effect in patients with androgen independent prostate cancer. In retrospect, it appears those initial reports failed to control for confounding variables such as antiandrogen withdrawal and hydrocortisone. Suramin causes numerous reversible toxicities (lethargy, rash, fatigue, anemia, hyperglycemia, hypocalcemia, coagulopathies, neutropenia, renal and hepatic complications). Neurotoxicity has been the most significant complication and appears to be related to the intensity of the dosing regimen. An optimal therapeutic dose has not been determined, but it is clear that adaptive controls add little benefit. Aside from moderate toxicities and the low therapeutic index in patients with prostate cancer, suramin's development has taught us some valuable lessons (i.e., anti-androgen withdrawal was noted during suramin's development, the use of PSA as an indicator of tumor burden was initiated during the evaluation of suramin). These lessons can be applied to all clinical trials in hormone refractory prostate cancer. Suramin has significantly enhanced the evolution of our knowledge in several areas of prostate cancer biology and treatment.
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PMID:Suramin's development: what did we learn? 1209 81

The antiangiogenic effects of thalidomide have been assessed in clinical trials in patients with various solid and haematological malignancies. Thalidomide blocks the activity of angiogenic agents including bFGF, VEGF and IL-6. We undertook an open-label study using thalidomide 100 mg once daily for up to 6 months in 20 men with androgen-independent prostate cancer. The mean time of study was 109 days (median 107, range 4-184 days). Patients underwent regular measurement of prostate-specific antigen (PSA), urea and electrolytes, serum bFGF and VEGF. Three men (15%) showed a decline in serum PSA of at least 50%, sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%. Increasing levels of serum bFGF and VEGF were associated with progressive disease; five of six men who demonstrated a fall in PSA also showed a decline in bFGF and VEGF levels, and three of four men with a rising PSA showed an increase in both growth factors. Adverse effects included constipation, morning drowsiness, dizziness and rash, and resulted in withdrawal from the study by three men. Evidence of peripheral sensory neuropathy was found in nine of 13 men before treatment. In the seven men who completed six months on thalidomide, subclinical evidence of peripheral neuropathy was found in four before treatment, but in all seven at repeat testing. The findings indicate that thalidomide may be an option for patients who have failed other forms of therapy, provided close follow-up is maintained for development of peripheral neuropathy.
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PMID:An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer. 1264 16

Preclinical studies suggest that the isoflavone genistein may have prostate cancer chemopreventive activity. Genistein has been shown to alter cellular levels of protein-tyrosine phosphorylation and is present at high levels in soy. This study was designed to measure the pharmacokinetic parameters of two different preparations of unconjugated soy isoflavones, PTI G-2535 and PTI G-4660 (which contain 43% and 90% genistein, respectively), in human subjects with cancer, to evaluate toxicity and obtain pilot data on in vivo effects on protein-tyrosine phosphorylation. Cohorts of four patients were given single doses of each preparation; each dose was separated by 1 week. Sequential cohorts received genistein at 2, 4, or 8 mg/kg orally. Pharmacokinetic sampling was performed after each dose, and tyrosine phosphorylation was measured in proteins extracted from peripheral blood mononuclear cells. One of 13 patients treated developed a treatment-related rash. No other toxicities were observed. Maximal plasma concentrations (C(max)) ranged between 4.3 and 16.3 micro M for total genistein and 0.066 and 0.17 micro M for free genistein. For PTI G-2535 and PTI G-4660, half-life was 15.03 and 22.41 h, respectively, and volume of distribution was 189.9 and 653.8 liters, respectively, and there was a trend toward higher area under the concentration curve for PTI G-2535 (P = 0.07 at the 8 mg/kg dose). Treatment-related increases in tyrosine phosphorylation were observed in peripheral blood mononuclear cells. Oral administration of soy isoflavones gives plasma concentrations of genistein that have been associated with antimetastatic activity in vitro.
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PMID:Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer. 1465 84


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