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)

Ketoconazole is an orally active antimycotic agent and a potent inhibitor of gonadal and adrenal steroidogenesis. As inhibitor of steroid production, it has been employed in Cushing's syndrome, prostatic cancer and precocious puberty due to autonomous Leydig-cell hyperfunction. By virtue of its selective action on androgen synthesis at low doses by inhibition of C17-20 lyase, this drug could be of potential therapeutic utility in hirsutism. We evaluated the hormonal and clinical effects of a low-dose regimen (400 mg/day) for 3 months in 16 women with a spectrum of disorders from idiopathic hirsutism to polycystic ovary syndrome. Four of them completed 6-month treatment. At 3 months, DHEA-S decreased from 9.9 +/- 1.0 (mean +/- SE) to 6.9 +/- 1.0 mumol/L (p less than 0.01), androstenedione from 13.3 +/- 1.5 to 8.3 +/- 1.3 nmol/L (p less than 0.005), and testosterone from 4.2 +/- 0.4 to 3.1 +/- 0.4 nmol/L (p less than 0.05). No significant changes were observed in LH, FSH, prolactin and estradiol levels. In patients treated for 6 months, androgens were within normal limits at the end of the study. Eleven out of 16 women (about 70%) reported some improvement in their hirsutism. There was a significant decrease in Ferriman-Gallwey's score (p less than 0.001) and mean hair-shaft diameter (p less than 0.001). The patients treated for 6 months showed a further improvement. Pelvic ultrasonography, when repeated (n = 8), was either unchanged or improved. Side effects (polymenorrhea, gastrointestinal reaction, somnolence) were generally mild and transient. Of 20 women who entered the study the dropout rate was 20% (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-dose ketoconazole treatment in hirsute women. 213 47

The objectives were to (1) prospectively evaluate fatigue utilizing validated instruments in patients with localized prostate cancer, and (2) examine the relationships between fatigue, depression, quality of life, and sleep disturbance. The instruments used included: Piper Fatigue Scale, Beck Depression Inventory, Epworth Sleepiness Scale, and Functional Assessment of Cancer Therapy for Prostate Scale. Data on cancer stage, prostate specific antigen levels, hematocrit, patient's body weight and radiation dosage were recorded. Patients were evaluated preradiotherapy, middle of radiotherapy, completion of radiotherapy, and at 4-5 weeks follow-up. Thirty-six veterans with localized prostate cancer were studied. Mean age was 66.9 years (range 55-79). Duration of treatment was 7-8 weeks. Univariate procedure and Wilcoxon Signed Rank-test were used to examine changes in pretreatment scores for each of the three subsequent study periods. To adjust for multiple comparisons Bonferroni test was used. Spearman Correlations were calculated among parameters. No significant changes were noted in mean scores of hematocrit and body weight during the study period. On the Piper Fatigue Scale, adjusted for multiple comparisons, the median scores were significantly higher at completion of radiotherapy as compared with preradiotherapy values. Three patients (8%) were experienced fatigue according to Piper Fatigue Scale before treatment as compared to nine patients (25%) at completion of radiotherapy. On Prostate Cancer Specific and Physical Well Being subscales of the Functional Assessment for Prostate Cancer Therapy, the scores were significantly lower at middle and completion of radiotherapy than at pretreatment. At preradiotherapy, middle of radiotherapy, completion of radiotherapy and follow-up evaluation, patients scoring higher on the Piper Fatigue Scale were more likely to report a poorer quality of Physical Well Being on Functional Assessment of Cancer Therapy for Prostates. No significant changes were noted in the Beck Depression Inventory and Epworth Sleepiness Scale scores during treatment. Eight patients scored 10 or more on the Beck Depression Inventory before starting radiotherapy, suggesting depressive symptomatology. Of these, only seven patients scored 10 or more at completion of treatment. The incidence of fatigue is lower in our study than in previously published data. A relationship exists between fatigue scores and physical well being subscale scores. Higher scores on the Piper Fatigue Scale at the completion of radiotherapy, as well as no changes on depression and sleepiness scales, suggest that fatigue may not be the result of depression or sleep disturbance. Based upon our previous work, we propose that the physical expression of fatigue may be secondary to a decline in neuromuscular efficiency and enhanced muscle fatigue.
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PMID:Prospective study of fatigue in localized prostate cancer patients undergoing radiotherapy. 1040 60

Therapy for benign prostatic hyperplasia has evolved rapidly over the last decade, with the introduction in the early 1990s of new agents such as alpha(1)-blockers and 5alpha-reductase inhibitors. The major advantage of alpha(1)-blockers over 5alpha-reductase inhibitors is their rapid onset of action. Maximum flow rate is improved after first administration and optimal symptom relief is usually reached within 2-3 months. In addition, alpha(1)-blockers are effective regardless of prostate size and they provide a similar degree of symptom relief in patients with or without bladder outlet obstruction. The main adverse events with the alpha(1)-blockers relate to their effects on the cardiovascular system (postural hypotension) and central penetration (asthenia, somnolence). Newer uroselective alpha(1)-blockers, such as alfuzosin and tamsulosin, have a better safety profile and, as such, do not require initial dose titration. Alfuzosin has also been shown in a six-month study to significantly reduce both residual urine and the incidence of acute urinary retention (AUR) compared with placebo. In addition, alfuzosin is effective in improving the success rate of a trial without catheter in patients with AUR.
Prostate Cancer Prostatic Dis 1999 Dec
PMID:alpha(1)-Blocker therapy in the nineties: focus on the disease. 1249 68

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

Thalidomide has re-emerged as a novel antineoplastic agent with immunomodulatory and antiangiogenic activities. In the early sixties, it was withdrawn from the market after its infamous association with congenital abnormalities that left about 10,000 children affected world-wide. With strict regulations and precautions, thalidomide is now approved by the FDA for the treatment of erythema nodosum leprosum. Its role in cancer therapy is promising, with clinical trials in the past 5 years showing significant activity in multiple myeloma. Several trials are ongoing in other malignancies, such as myelodysplastic syndrome, agnogenic myeloid metaplasia, renal cell carcinoma, and prostate cancer. The major toxicities of thalidomide are birth defects, sensorimotor peripheral neuropathy, somnolence, rash, fatigue, and constipation. Less common side effects include deep venous thrombosis, Stevens-Johnson syndrome, elevated liver enzymes, malaise, and peripheral edema. The incidence and severity of adverse events are related to dose and duration of therapy. Doses of the drug of 200 mg/day or less are usually well tolerated. In this review, we will discuss the incidence and management of the side effects of thalidomide and the precautions and interventions needed to minimize the toxicities of this drug.
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PMID:Management of thalidomide toxicity. 1533 75

Thalidomide, a glutamic acid derivative, was withdrawn from clinical use in 1962 due to its severe teratogenic effects. Its recent reinstitution in clinical practice was related to its benefits in leprosy and multiple myeloma. Moreover, the antiangiogenic and immunomodulatory properties of thalidomide have led to its evaluation in several malignant diseases, including myelofibrosis, renal cell cancer, prostate cancer, and Kaposi sarcoma. However, thalidomide use is associated with several side effects: somnolence and constipation are the most common, while deep vein thrombosis and peripheral neuropathy are the most serious. A combination of thalidomide with steroids or chemotherapy is being evaluated in several phase 2 studies. While it is not yet clear whether these combinations will enhance efficacy, they appear to increase the toxicity of thalidomide, and thalidomide analogs are being developed to minimize this toxicity. Ongoing studies will clarify the potential advantages of these agents in the treatment of neoplastic diseases.
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PMID:Adverse effects of thalidomide administration in patients with neoplastic diseases. 1546 8

Thalidomide has anti-angiogenic and immunomodulatory activity, exhibiting antitumour effects in patients with multiple myeloma and, more rarely, in several other solid tumours. We evaluated the single-agent antitumour activity and toxicity profile of thalidomide in patients with metastatic malignant melanoma, as well as its plasma pharmacokinetics and pharmacodynamic effects [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) levels]. A two-stage Gehan method was used with a stopping rule after 14 consecutive non-responding patients. Thalidomide was given orally at a daily dose of 200 mg/day, which was then escalated every 2 weeks by 200 mg/day as tolerated to a maximum of 800 mg/day. Patients were evaluated every 8 weeks for response using the World Health Organization (WHO)-27 criteria. Fourteen patients were enrolled and no objective responses were observed, with one stable disease and one mixed response. The dose-limiting toxicities were constipation, dizziness and somnolence. Other toxicities were oedema, neuropathy, dry skin, dry mouth, tremor and fatigue. The plasma pharmacokinetics of thalidomide were comparable with those of previous studies in normal volunteers and in patients with advanced prostate cancer. Serum levels of b-FGF and VEGF did not change significantly following drug administration. In conclusion, thalidomide showed poor activity, but acceptable toxicity, in patients with metastatic melanoma. Future studies should explore this agent in combination with other biological agents or cytotoxic agents, such as temozolomide.
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PMID:Phase II study of thalidomide in patients with metastatic malignant melanoma. 1557 25

This study prospectively evaluated quality of life (QOL) in localized prostate cancer patients undergoing radiotherapy, and it examined the relationships between QOL, depression, fatigue, and sleep disturbance. Instruments that were used are Functional Assessment of Cancer Therapy for Prostate (FACT-P), Beck Depression Inventory (BDI), Piper Fatigue Scale (PFS), and Epworth Sleepiness Scale (ESS). We evaluated patients at preradiotherapy (PRT), midway radiotherapy (MRT), completion of radiotherapy (CRT), follow-up radiotherapy (4 to 8 wk) (FRT), and long-term follow-up radiotherapy (FRT2) (12 mo or more). Forty participants with a mean age of 67.8 yr were studied. Duration of radiotherapy was 7-8 wk. Mean long-term follow-up period post-CRT was 16.2 mo (range 12- 24 mo). All patients had clinical T1c to T2b prostate cancer. Prostate Cancer Specific (PCS) and Physical Well-Being (PWB) subscales of FACT-P, scores at MRT and CRT were significantly lower than at PRT. At FRT2, PWB scores declined further, while PCS scores increased. PFS median scores were significantly higher at CRT and at FRT2 as compared with PRT. Patients scoring higher on PFS were more likely to report a poorer QOL and PWB as measured with FACT-P questionnaire. No significant changes were noted in the BDI and ESS scores during the study periods. The PWB declined during and at CRT and worsened at FRT2. Decline in PCS subscale scores during and at CRT reflects worsening of urinary symptoms and appearance of bowel problems. The scores improved at long-term follow-up. A relationship was found to exist between physical well-being and fatigue.
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PMID:Longitudinal study of quality of life in patients with localized prostate cancer undergoing radiotherapy. 1618 51

Advanced prostate cancer with skeletal metastases entails significant symptoms from both treatment and the disease itself. Although the diagnosis is a common one, knowledge of the symptom experience late in the disease trajectory is limited. The aim of the present study was to describe the experience of physical symptoms in men with hormone refractory prostate cancer and skeletal metastases. Twenty men answered a quality of life questionnaire before participating in semi-structured interviews. The interviews were analyzed using qualitative description. Findings show that the dominant symptoms were lack of energy and pain. Interestingly when talking about lacking energy the men described three different variants; lack of mental energy or initiative, lack of strength and stamina, and tiredness or sleepiness. Also, three different types of pain were described; pain from skeletal metastases, a diffuse moving pain, and pain not directly caused by the prostate cancer. Though a majority of the men scored being dissatisfied with their sex life; in the interviews, this was not described as a major distress. The findings also showed that the men experienced different symptoms despite the same diagnosis, skeletal metastases, stage, and androgen deprivation treatment, and that these symptoms are not necessarily experienced as problems or causing distress.
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PMID:Experiences of symptoms in men with hormone refractory prostate cancer and skeletal metastases. 1844 Aug 62

A limited body of evidence suggests that sleep problems are common in prostate cancer patients undergoing androgen deprivation therapy, yet little is known about sleep characteristics and the effects of poor sleep on daily functioning in this population. This study assessed sleep in 60 prostate cancer patients taking androgen deprivation therapy with wrist actigraphy and daily diaries for 7 days. The Epworth Sleepiness Scale and the general version of the Functional Assessment of Cancer Therapy scale were also administered. On average, total sleep time was 5.9 (SD = 1.4) h, and sleep efficiency was 75% (SD = 12.0) as assessed by actigraphy. There was generally poor concordance between actigraphy and daily diary for most sleep metrics. Subjects reported awakening, on average, 2.7 times per night, most commonly for nocturia and hot flashes. Assessment of daily functioning showed that participants had mild daytime sleepiness, which was predicted by total sleep time (F(1,47) = 4.5, P= 0.04) General quality of life was not impaired. This study supports more research on the predictors of poor sleep in order to identify effective interventions.
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PMID:Sleep and daily functioning during androgen deprivation therapy for prostate cancer. 2082 64


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