Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-eight and 24 patients with advanced breast cancer were treated with Aminoglutethimide (AG) or AG + Tamoxifen (AG + TAM) from June 1984 to June 1989, respectively. Evaluated cases were 25 and 21 treated with AG or AG+TAM, respectively. Objective response was seen in 5/25 (20.0%) for AG treatment with 9, 13, 16, 20 and 31 months remission and 4/21 (19.1%) for AG + TAM treatment with 6, 7, 12 and 26 months remission. Response rate according to dominant site of metastases were 1/10 in soft tissue, 2/7 in bone, 2/7 in lung and pleura treated with AG, 1/9 in soft tissue, and 3/5 in lung treated with AG + TAM treatment. Two of the 5 responding patients in AG treatment group had prior tamoxifen treatment and 3 out of 4 responding patients in AG + TAM treatment group had prior chemoendocrine therapy with tamoxifen and FAC chemotherapy. Main toxic side effects were lethargy and/or rash, and drug discontinuation was required in 3 cases of AG treatment group and 2 cases of AG + TAM treatment group. Serial determination of serum hormone levels during AG or AG + TAM treatment revealed a decrease in estrone and an increase in androstenedione in many cases of both treatment groups. This data suggested that AG treatment may be favorable for endocrine treatment for advanced breast cancer patients, but the response to AG was not augmented by adding TAM.
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PMID:[Aminoglutethimide and aminoglutethimide+tamoxifen treatment for advanced breast cancer]. 141 9

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

Eighty-seven consecutive patients with metastatic breast cancer were treated with aminoglutethimide plus hydrocortisone. All patients were postmenopausal and had progressive disease following prior chemotherapy and endocrine therapy. Eighty-five women were evaluable for drug response. One patient showed complete remission and 14 patients partial response, for an overall response rate of 17%. The median duration of response was 11+ months. The response rate was highest in the presence of soft tissue involvement (36%). The most common side effects were transient skin rash, lethargy, and dizziness. Two patients discontinued treatment because of cutaneous allergy. Aminoglutethimide can be considered a moderately active agent when utilized as second- or third-line hormonal therapy.
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PMID:Aminoglutethimide in postmenopausal breast cancer refractory to multiple hormonal and cytostatic treatments. 366 Apr 75

Two hundred and thirteen unselected postmenopausal women with advanced breast cancer were treated with aminoglutethimide and hydrocortisone. There were 6 complete responses (CR), 47 partial responses (PR), 25 stable disease (SD) and 3 mixed response. Overall objective response rate was 28%, and with SD 41%. Median duration of objective response was 14 months. Years after menopause, age and tumour-free interval did not affect response rates. Main side-effects were drowsiness and lethargy (33%), rash (23%) and nausea (15%). Eleven patients (5%) stopped treatment because of toxicity. Median survival from start of treatment was 28 months and was the same for CRs, PRs and SD, compared with 10 months for progressive disease (P less than 0.001). Median survival from first metastasis was 43 months for PR/CR, 40 months for SD (not significantly different) and 22 months for progressive disease (P less than 0.001). Aminoglutethimide is an effective endocrine therapy in advanced postmenopausal breast cancer, particularly for bone deposits. Disease stabilization is associated with symptomatic and survival benefit similar to CR/PR.
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PMID:Aminoglutethimide for the treatment of advanced postmenopausal breast cancer. 668 69

In a control randomized cross-over trial, 117 patients with advanced breast cancer were treated initially either with tamoxifen (10 mg p.o. twice daily) or aminoglutethimide (250 mg p.o. 4 times daily) with hydrocortisone (20 mg twice daily). Patients failing to respond or relapsing were switched to the alternative treatment. Eighteen (30%) of the 60 patients initially treated with tamoxifen achieved an objective response, and 11 (18%) achieved stable disease. Seventeen (30%) of the 57 patients treated initially with aminoglutethimide achieved an objective response, and 13 (23%) achieved stable disease. Aminoglutethimide achieved a 35% objective response and a further 26% subjective bone pain relief in patients with bone metastases (overall, 61%) compared with a 17% objective response and a further 17% objective bone pain relief with tamoxifen (total, 34%). None of six premenopausal patients responded to aminoglutethimide compared with two of four responding to tamoxifen. The median response duration to aminoglutethimide was 16 months compared with 20 months for tamoxifen. Side effects for aminoglutethimide (including lethargy, rash, and depression) were more common than for tamoxifen, and 7% of aminoglutethimide-treated patients had to discontinue treatment because of these compared with 0% on tamoxifen. In cross-over studies, 6 of 12 tamoxifen responders who relapsed achieved a second response to aminoglutethimide (50%), as did 6 of 29 patients who initially failed to respond to tamoxifen (21%). In contrast, none of 11 patients relapsing after response to aminoglutethimide achieved a second response to tamoxifen; only 1 of 18 nonresponders to aminoglutethimide subsequently responded to tamoxifen (6%). In a subsequent study in which 62 patients were treated with combined tamoxifen and aminoglutethimide, the overall response rate of 37% was not significantly better than that for either agent used alone.
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PMID:Tamoxifen versus aminoglutethimide versus combined tamoxifen and aminoglutethimide in the treatment of advanced breast carcinoma. 704 25

Aminoglutethimide in combination with dexamethasone has been used in 44 patients with metastatic breast cancer who had prior response to hormonal manipulation and/or positive estrogen receptors. Objective tumor response (complete response plus partial response) has been achieved in 19 of 44 patients. Responses were seen in soft tissue, bone, and pleura. Eleven of 44 patients had stable disease, and 14 patients had progressive disease. The median duration of response was 8 months. Side effects were moderate, including lethargy, rash, fever, and Cushingoid facies. This treatment is well tolerated and is an effective hormone manipulation in postmenopausal patients with metastatic breast carcinoma.
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PMID:Aminoglutethimide in the treatment of metastatic breast cancer. 708 6

Aminoglutethimide (Elipten), at a dosage between 250 and 1500 mg/d by mouth, was administered in a clinical phase II study to 17 patients with metastasizing carcinoma of the breast resistant to hormones and cytostatic drugs. Results of this treatment were available for 14 patients. Nine women were given the drug alone, eight in combination with cytostatic drugs. In 11 women the drug significantly decreased pain within 3-14 days. Used alone aminoglutethimide produced objective regression of the metastases in two women, two further instances of regression occurred when the drug was combined with cytostatic agents. Five women developed urticarial rash, while six had somnolence and nausea or lethargy. Aminoglutethimide is suitable for symptomatic treatment of metastasizing treatment-resistant carcinoma of the breast, either alone or in combination with cytostatic drugs.
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PMID:[Aminoglutethimide in metastasizing carcinoma of the breast resistant to hormonal and cytostatic treatment (author's transl)]. 727 74

Aminoglutethimide (AG) with Dexamethasone has been utilized in 26 patients with metastatic breast cancer who had prior response to hormonal manipulation and/or positive estrogen receptor. Objective tumor response (CR + PR) has been achieved in 13 of 26 patients. Responses were seen in soft tissue, bone, and pleura. Six of 26 patients had stable disease and seven of 26 patients had progressive disease. The median duration of response is 12.8 months. The median survival for the responders has not been reached. Non-responding patients had a median survival of five months. Side effects were minimal, including mild lethargy, rash, fever, and weight gain. This regimen is well tolerated and can be used effectively in metastatic hormone-receptor-positive breast cancer.
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PMID:Aminoglutethimide in the management of metastatic breast cancer. 746 86