Ketoconazole | Health and Prostate

Posts Tagged ‘Ketoconazole’

Spinal Cord Compression and Other Complications of Osseous Metastases

Posted by admin on June 21st, 2011 No Comments

Complications of osseous metastases include spinal cord compression, seen ultimately in 10% of men with prostate cancer (which is second only to lung cancer as an etiologic cause), pathologic vertebral compression fracture, pathologic long bone fracture (most commonly of the femur and humerus), hypercalcemia, and bone marrow failure. Nearly all patients with complications of osseous metastases complain of pain. In the case of spinal cord and nerve root compression, decreased sensation usually precedes motor symptoms and may be detected on careful examination. Magnetic resonance imaging is frequently used to evaluate spinal cord compression, due to its high sensitivity and ability to image the vertebral bodies and paraspinal and intraspinal soft tissues. On Tl-weighted images, bone metastases tend to stand out as focal or diffuse hypointense (dark) lesions against a background of higher signal intensity marrow. Compared to myelography, magnetic resonance imaging is noninvasive, directly visualizes cord compression, and can measure the extent of tumor outside the thecal sac along the entire cord. In Read more [...]

Posted in Prostate Cancer

Combination Chemotherapy

Posted by admin on June 21st, 2011 No Comments

With a few notable exceptions, reported combinations of cytotoxic chemotherapeutic agents have added little benefit to single-agent chemotherapy in the treatment of hormone-refractory prostate cancer. It must be emphasized that early trials of combination chemotherapy were performed in the pre-prostate-specific antigen era with patients exhibiting very advanced and usually symptomatic hormone-refractory prostate cancer. In addition, an understanding of basic prostate cancer biology has provided insights for the rational selection of drug combinations such as Estramustine phosphate and paclitaxel targeting the cytoskeleton and nuclear matrix. Cytoxan + Methotrexate + 5-Fluorouracil The regimen of cytoxan (Cy), methotrexate, and 5-FU (CMF) is a combination active in epithelial malignancies including breast carcinoma. This regimen was evaluated in 52 eligible patients with measurable (19 patients), evaluable (29 patients), or bone scan only (4 patients) metastatic prostate cancer using a dosing schedule of 100 mg per m per day by mouth of cyclophosphamide, 15 mg per m weekly IV methotrexate, and Read more [...]

Posted in Chemotherapy and Immunotherapy

Secondary Hormonal Therapy

Posted by admin on June 21st, 2011 No Comments

Metastatic prostate cancer that progresses after initial androgen deprivation is most commonly referred to as hormone-refractory prostate cancer or androgen-independent prostate cancer. Both these labels are misleading, as Fowler and Whitmore et al. and Manni et al. proved in their findings that the disease flares when exogenous testosterone is given. Likewise, it becomes quiescent again on discontinuation of the exogenous androgen. These clinical observations strongly suggest that the disease is not refractory to or independent of growth stimulation by exogenous testosterone. Thus, there is debate about the role of low levels of endogenous adrenal androgens and that of continued suppression of testicular androgen production by means of luteinizing hormone-releasing hormone agonists. In two retrospective analyses, the question was asked whether androgen deprivation should be continued or maintained when the "hormone-refractory" state was reached. The hormone-refractory state was defined clinically as the need for chemotherapy. In a 341 patient cohort studied by the Eastern Cooperative Oncology Read more [...]

Posted in Hormonal Therapy

Second-Line Antiandrogens

Posted by admin on June 21st, 2011 No Comments

The addition of flutamide at the time of progressive metastatic disease is associated with an objective response in 15% and disease stabilization in 20% of patients (Table Secondary Hormonal Manipulation: Addition of Flutamide ). Patients treated on the placebo arm of the National Cancer Institute's Intergroup protocol 0036 comparing leuprolide and flutamide versus leuprolide and placebo, however, showed no survival benefit when flutamide was added at the time of disease progression. TABLE. Secondary Hormonal Manipulation: Addition of Flutamide Inhibits uptake and binding of androgen to the androgen receptor 230 patients, five trials: 15% objective response, 20% stable disease No obvious survival benefit in one phase III trial Toxicities: diarrhea, gynecomastia, abnormal liverfunction tests Recently, Fowler et al. reported an 80% prostate-specific antigen response rate in the same population. The role of flutamide in men progressing after treatment with another antiandrogen or its withdrawal has not been studied but is expected by many authorities to have some Read more [...]

Posted in Hormonal Therapy

Inhibitors of P-450-Dependent Enzymes

Posted by admin on June 21st, 2011 No Comments

Ketoconazole is an antifungal agent that inhibits both sterol membrane synthesis and the cytochrome P-450-dependent enzyme 17,20-lyase (CYP34A). At high doses, it effectively blocks both testicular and adrenal androgenesis. This suppressive effect on testosterone was first investigated based on the development of unexpected gynecomastia in early clinical trials for dermato-mycoses. Multiple studies of ketoconazole without glu-cocorticoids done in the pre-prostate-specific antigen era (N=15), reviewed by Dawson, demonstrated objective responses in approximately 16% of patients and stable disease in an additional 3o . In the prostate-specific antigenera, Gerber and Chodak, again using ketoconazole alone, reported zero of nine patients to have a > 50% decline in prostate-specific antigen level, although two of nine had excellent clinical responses. Ketoconazole combined with hydrocortisone in men progressing after antiandrogen withdrawal produced a > 50% decline in prostate-specific antigen in 30 (62.5%) of 48 evaluable patients for a median 3.5 months. Response was not influenced by prior response Read more [...]

Posted in Hormonal Therapy

Progesterones and Estrogens

Posted by admin on June 21st, 2011 No Comments

Megestrol acetate has several mechanisms of action that suggest a potential beneficial role in treating progressive metastatic prostate cancer. It inhibits the release of luteinizing hormone, 5 a-reductase conversion of testosterone to dihydrotestosterone, binding of androgen to its receptor, and at high doses may be cytotoxic. Based on clinical reports that suggest a dose-response effect, Dawson et al. studied two doses for the CALGB (160 mg versus 640 mg). The prostate-specific antigen response was only 12%, however, with no dose effect and no association with prior response to antiandrogen withdrawal. An unexpected tumor flare was observed in some patients, suggesting that megestrol acetate had agonistic activity. There was a similar low response rate reported in a smaller retrospective study. The palliative benefit of both estrogens and orchiec-tomy in the treatment of advanced prostate cancer was first reported in 1941, by Huggins and Hodges. In the setting of hormone-sensitive disease, the inhibitory effect of estrogen is due to suppression of pituitary gonadotropins and in turn testosterone. Read more [...]

Posted in Hormonal Therapy

Current Therapies

Posted by admin on May 6th, 2011 No Comments

The main treatment modalities for prostate cancer (CaP) include "watchful waiting"; local therapy (prostatectomy or radiotherapy, either external beam radiation therapy [EBRT] or brachytherapy); hormonal therapy; and chemotherapy. Watchful waiting is generally reserved for elderly men, who, because of short life expectancy or slowly progressing disease, are likely to die with CaP rather than because of CaP. Local therapies alone can often cure patients diagnosed with early-stage (I or II) prostate-confined disease. Hormonal therapy is used primarily to delay disease progression when local therapies have failed. Chemotherapy is generally reserved for hormone-refractory disease to palliate symptoms. A growing trend in CaP treatment is the use of intermittent therapy. Hormonal therapies are often administered for three years or more as adjuvant therapy. Although their sideeffect profile is mild compared with that of many chemotherapy agents, they do have several undesirable effects (e.g., hot flashes, sexual dysfunction, gynecomastia [excessive development of mammary glands]). To reduce these side Read more [...]

Posted in Prostate Cancer

Docetaxel

Posted by admin on November 8th, 2010 No Comments

(British Approved Name, US Adopted Name, rINN) Drug Nomenclature International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish): Synonyms: Docetaxel; Docetaxol; Docetaxolum; Dosetaksoli; NSC-628503; RP-56976 BAN: Docetaxel USAN: Docetaxel INN: Docetaxel [rINN (en)] INN: Docetaxel [rINN (es)] INN: Docétaxel [rINN (fr)] INN: Docetaxelum [rINN (la)] INN: Доцетаксел [rINN (ru)] Chemical name: (2R,3S)-N-Carboxy-3-phenylisoserine, N-tert-butyl ester, 13-ester with 5β-20-epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4-acetate 2-benzoate; tert-Butyl {(1S,2S)-2-[(2S,5R,7S,10R,13S)-4-acetoxy-2-benzoyloxy-1,7,10-trihydroxy-9-oxo-5,20-epoxytax-11-en-13-yloxycarbonyl]-2-hydroxy-1-phenylethyl}carbamate Molecular formula: C43H53NO14 =807.9 CAS: 114977-28-5 (anhydrous docetaxel); 148408-66-6 (docetaxel trihydrate) ATC code: L01CD02 Read code: y08Xn Adverse Effects, Treatment, and Precautions As for Paclitaxel. Neutropenia, anaemia and skin reactions are common with docetaxel and may be severe. Fluid retention, resulting in oedema, Read more [...]

Posted in Drugs

Mechanisms of androgen axis blockade

Posted by admin on June 25th, 2010 No Comments

There are four therapeutic approaches for androgen axis blockade in current clinical use: ablation of androgen sources, inhibition of androgen synthesis, antiandrogens, and inhibition of luteinizing hormone–releasing hormone (LHRH) or luteinizing hormone (LH) release ( Table: Therapeutic Approaches to Androgen Deprivation Therapy ). Table: Therapeutic Approaches to Androgen Deprivation Therapy[*] Ablation of Androgen Sources Inhibition of Androgen Synthesis Antiandrogens Inhibition of LHRH or LH Orchiectomy Aminoglutethimide Cyproterone acetate DES Ketoconazole Leuprolide Flutamide Goserelin Bicalutamide Triptorelin Nilutamide Histrelin Cetrorelix Abarelix DES, diethylstilbestrol; LH, luteinizing hormone; LHRH, luteinizing hormone–releasing hormone. * Several agents have multiple mechanisms of action. Ablation of Androgen Sources Bilateral orchiectomy quickly reduces circulating testosterone levels to less than 50 ng/dL, which, on the basis of this procedure, is considered the castrate Read more [...]

Posted in Treatment

Alfuzosin Hydrochloride

Posted by admin on June 8th, 2010 No Comments

Drug Approvals (British Approved Name Modified, US Adopted Name, rINN) International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish): Alfutsosiinihydrokloridi; Alfuzosin Hidroklorur; Alfuzosine, chlorhydrate d' Alfuzosin-hydrochlorid; Alfuzosinhydroklorid; Alfuzosini hydrochloridum; Alfuzozin-hidroklorid; Alfuzozino hidrochloridas; Hidrocloruro de alfuzosina; SL-77499-10; SL-77499 (alfuzosin). Pharmacopoeias. In Europe. European Pharmacopoeia, 6th ed. (Alfuzosin Hydrochloride). Awhite or almost white, slightly hygroscopic, crystalline powder. Freely soluble in water sparingly soluble in alcohol practically insoluble in dichlo-romethane. A 2% solution in water has apH of 4.0 to 5.5. Store in airtight containers. Protect from light. Adverse Effects, Treatment, and Precautions As for Prazosin Hydrochloride. Alfuzosin may be more selective for the urinary tract and vasodilator effects may be less frequent. It should be avoided in severe hepatic impairment, and doses may need to be reduced in mild to moderate hepatic impairment and in renal impairment (see below). Incidence Read more [...]

Posted in Drugs

Posts Tagged ‘Ketoconazole’

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