Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The optimal dose of progesterone compounds for the treatment of breast cancer is unknown, but there is evidence to suggest a dose-response curve. We are testing the tolerability and efficacy of megestrol acetate administered orally and continuously in doses three to ten times higher than the standard dose of 160 mg/d. We have so far treated 33 patients with metastatic breast cancer and positive or unknown tumor hormone receptor status. Thirty patients had had documented disease progression with previous hormonal therapy, and 22 had failed with previous chemotherapy. Twenty-five patients had objectively measurable metastases. In this heavily pretreated group, the objective response rate was 40%; in addition, 32% of patients had stabilization of disease. Interestingly, ten of 12 patients who had developed disease progression while on standard-dose megestrol acetate therapy had objective response or stabilization on the higher dose. Toxicity was acceptable and reversible and included mild elevations of blood pressure and weight gain. Our results indicate that high-dose megestrol acetate is well-tolerated and highly active in advanced refractory breast cancer, and suggest a dose-response curve for the drug in the treatment of breast cancer.
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PMID:High-dose megestrol acetate in the treatment of postmenopausal women with advanced breast cancer. 379 25

Weight loss and anorexia are significant complications of a variety of disorders and add morbidity to the underlying process. We observed marked weight gain (median, 5.1 kg; range, 0.9 to 20.1 kg) and appetite enhancement in 27 of the 28 patients with breast cancer receiving treatment consisting of high doses of oral megestrol acetate (480 to 1600 mg/d). Weight gain occurred regardless of pretreatment weight, extent of metastases, or response to therapy. Our results suggest a possible role for megestrol acetate in reversing anorexia and weight loss, thereby improving the quality of life of patients with cachexia. Further research is needed to establish the mechanism of weight gain and potential clinical applications.
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PMID:High-dose megestrol acetate. A possible treatment for cachexia. 380 18

Spinal cord or cauda equina compression secondary to epidural metastasis rarely develops in patients with endometrial carcinoma and the early signs and symptoms of compression can therefore be inadvertently overlooked. A 78-year-old patient who developed bone metastasis with destruction of the fifth lumbar vertebral body and blockage of the cauda equina at L-4, L-5 as the only sites of metastasis is reported. This occurred 2 years after initial treatment of a stage IB, well-differentiated, grade I, adenosquamous carcinoma of the endometrium. The patient remains alive, with good neurological function and free of metastatic disease, 2 1/2 years following vertebrectomy, radiation therapy, and adjuvant Provera (medroxyprogesterone acetate) therapy. This patient represents the only case of metastatic endometrial cancer with cauda equina compression in the literature in whom long-term disease-free follow-up has been noted.
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PMID:Cauda equina compression secondary to metastatic carcinoma of the uterine corpus: preservation of neurologic function and long-term survival following surgical decompression and radiation therapy. 397 89

A 7 year study of megestrol and chlormadinone in female dogs is in progress. This report characterized histopathologically 60 mammary nodules during the first 4 years of the study. 100 purebred female beagles, 6-12 months of age, were randomly assigned to 5 equal groups. One group was used as a control. Oral doses were .01, .10, and .25 mg/kg/day of megestrol acetate in coconut oil in capsules and of chlormadinone acetate .25 mg/kg/day in lactose tablets. These doses were 1, 10, and 25 times the projected dose of megestrol for humans and about 25 times the human dose of chlormadinone. After 2 years 4 dogs from each group were necropsied. One high-dose megestrol-treated and 1 chlormadinone-treated dog had benign mixed mammary tumors. Palpable nodules were first observed at 16 months in the chlormadinone-treated dogs, at 18 months in dogs given the high dose megestrol and at 27 months in the dogs treated with middle-dose megestrol. Transitory nodules were found in 4 control dogs after 21 months and in low dose megestrol-treated dogs at 26 months. Of 38 grossly detected nodules evaluated microscopically from the megestrol-treated dogs 27 were nodular hyperplasia, 5 were benign mixed mammary tumors, 3 were ductal dialatations, 1 was a lymph node, 1 was fat necrosis and 1 was the umbilicus. Of 22 nodules from the chlormadinone-treated dogs 12 were nodular hyperplasia, 4 benign mixed mammary tumors, 1 chondromucoid degeneration and 1 adenocarcinoma with widespread metastases. 3 nodules were lymph nodes and 1 other had no mammary tissue. Involutions, regression and sclerosis of many areas of nodular hyperplasia were evident at 4 years. Thus of the 60 nodules evaluated during the first 4 years of the study 50 were non-neoplastic and 10 were neoplastic. It is considered that the 1 adenocarcinoma may have been spontaneous and not a treatment-related neoplasm. A precursor stage through nodular hyperplasia apparently did not occur.
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PMID:Mammary nodules in dogs during four years' treatment with megestrol acetate or chlormadinone acetate. 412 57

The prolonged administration of large doses of medroxyprogesterone acetate (MPA) in the treatment of patients with disseminated breast cancer was studied. The patients consisted of 17 postmenopausal women previously treated with 1 or more hormones (group I), 17 women (oophorectomized or postnatural menopause) who had received MPA prior to the study (group II), and 2 males with breast carcinoma (group III). Patients received MPA intramuscularly (as Depo-Provera, 100 mg 3 times weekly, 34 patients) or orally (as Provera, 100 mg daily, 2 patients), in all except 4 cases for a minimum of 5 weeks. Patients were classified as showing objective tumor regression or as being treatment failures. 4 patients, because of treatment for neurological complications, were judged not evaluable. 5 group-I patients and 2 group-II patients (both greater than 10 years since menopause) experienced objective tumor regression. All 7 patients received the MPA parenterally. By the end of the study mean duration of the objective remissions was 12 months. 3 of the 7 patients continued in remission at writing, 2 had succumbed to the disease, and 2 were receiving other agents. Site of involvement in these patients was predominantly osseous (3), visceral (2), or soft tissue (2). Mean age of the 7 responders was 69. The mean "free interval" from initial therapy to clinical appearance of distal metastases was 44 months in the responders. All 5 patients from group I had benefited from previous hormonal alterations. Of 10 patients receiving estrogens in combination with MPA immediately after the course of MPA alone, 5 demonstrated objective tumor regression, 1 who had responded to MPA alone. The best response in this group occurred in a 61-year old man. Most patients had no untoward effects with MPA administration. A fairly extensive discussion of the literature on MPA is included.
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PMID:Treatment of breast cancer with medroxyprogesterone acetate. 430 26

This study describes the effects of medroxyprogesterone acetate on tumor growth and metastases in transplanted uterine adenocarcinoma cells of the rat. High-and-low-tumorigenic cloned cells of Sprague-Dawley rat uterine adenocarcinoma originally induced by 7,12-dimethylbenz (alpha) anthracene in vivo were used. Both were derived from the same parent culture. They were cultured for more than 2 years and both retained almost the same transplantability. Survival rate of cell colonies in vitro was reduced in both lines after progesterone treatment of more than 8 mcg per ml. This reduction was dose dependent. About 1 million cells suspended in .2 ml culture medium were injected sc into the interscapular region of isologous newborn rats. At 5 weeks these rats were given .5 mg medroxyprogesterone acetate twice a week for 2 weeks. At 7 weeks they were killed. High-tumorigenic cells produced growing tumors in all newborn rats. About a third of these rats died of metastases during the 7-week observation period. Tumors produced by low-tumorigenic cells grew slowly and occasionally regressed without metastases to the lung. Tumors in female rats were larger than those in males. Enhancement of tumor growth and metastases by this progesterone compound was observed in rats inoculated with low-tumorigenic cells as compared to controls. The enhancement was not significant in tumors produced by high-tumorigenic cells. The progesterone may act immunosuppressively in vivo, or make alterations in environmental conditions of the tumors.
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PMID:Enhancement of tumor growth and metastases by medroxyprogesterone acetate in transplanted uterine adenocarcinoma cells of the rat. 481 Sep 70

Since 1963 there have been 266 patients with cancer of the uterine fundus at the Medical University of South Carolina. Progestational agents were used to treat 54 but 10 received the drugs for less than 1 month. This report relates to the remaining 44. 34 were treated with Depo-Provera (medroxyprogesterone acetate), 9 with Colprone (megestrone acetate), and 1 with Megace (megestrol acetate). Of the 34 patients treated with Depo-Provera 13 showed regression of the tumor; 3 of the 9 treated with Colprone showed regression. In an additional 11 (25%) of cases growth of the tumors was arrested. 7 of these were later found to have abdominal metastases; however, 3 were free of symptoms for over 43 months. A patient on Depo-Provera with lung metastases had recurrence after 62 months when treatment was reduced to every other week but when Colprone was then given, regression again occurred and has continued for almost 10 years. Another patient not responding to Depo-Provera did respond to Colprone. Average duration of regression was 27.7 months, of survival 31.1 months. Arrest of growth was 25 months in some; survival averaged 23.4 months. (The 1 Megace case was in this group.)y Those having progression of tumors lived an average of 9 months with the longest survival 24 months. Of the responders 8 lived from 44 to 111 months and 5 remain alive, 4 now showing no evidence of the cancer. Tumors with well-differentiated, slow-growing lesions were most likely to respond. Site of recurrence did not seem to influence the response. No contraindications were found to use of progestational agents in this type of cancer. Local reactions to the injections were few. Subjective response was frequent even though progression was taking place.
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PMID:Use of progestational agents in endometrial adenocarcinoma. 483

Eighty patients with advanced metastatic renal cancer have been treated with hormones, chiefly medroxyprogesterone acetate (Provera). This progestational compound is remarkably free from side-effects and can be given in high dosage for long periods without serious complications. Ninety per cent of cases had multiple metastases: in 76% more than one organ was involved and nearly 50% were seriously ill or "terminal".Subjective improvement occurred in at least 55%. In 11 patients there was marked improvement in the radiological or clinical signs of tumour within 2 to 6 weeks of commencing treatment or changing to a different hormone. In two further cases improved general health was associated with stationary metastases for 20 months. A significant objective response occurred in 16% of the total series. A favourable response was seen more often in men (21%) than in women (8%). If deaths within 6 weeks are excluded the objective response rate in men is increased to 27%. Although the response of advanced renal cancer to hormonal treatment is usually incomplete and of brief duration, it is possible for such treatment to offer a "new lease of life" to a seriously ill patient, even in old age, for 2 to 3 years.
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PMID:Medroxyprogesterone acetate (Provera) in the treatment of metastatic renal cancer. 511 27

The effect of the progestogen medroxyprogesterone acetate on metastases from renal, endometrial and other tumours has been studied in 25 patients. Seven patients with renal and endometrial tumours had a useful response, pulmonary metastases and a large primary renal tumour showing the greatest effect. Bony metastases were unaffected by the drug and were treated by local radiotherapy. If a response occurred, it did so within 3 months.
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PMID:The use of progestogen in the treatment of metastatic carcinoma of the kidney and uterine body. 545 69

We describe a simple, rapid, and reproducible ion exchange mini-column chromatographic method for the quantitative measurement of biliary alkaline phosphatase in plasma. We have used this method to evaluate a cellulose acetate electrophoretic method, which was used to assess the value of measuring biliary alkaline phosphatase in 85 patients with breast cancer investigated for possible hepatic metastases. Biliary alkaline phosphatase activity was abnormal in 19 of 24 patients (79%) with liver metastases, but abnormalities were also found in 12 of 61 patients (20%) without hepatic metastases; in only 37% of patients with positive test results was this a consequence of liver metastases. For the identification of liver metastases, therefore, the method has useful sensitivity but limited specificity. Neither sensitivity nor specificity was significantly better than that of plasma gamma-glutamyltransferase activity, which was measured concomitantly.
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PMID:Measurement of biliary alkaline phosphatase by mini-column chromatography and by electrophoresis and its application to the detection of liver metastases in patients with breast cancer. 614 Nov 85


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