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)

There are 36 reported cases of metastatic pituitary carcinoma and almost half (44%) of these were associated with syndromes of hormonal hypersecretion. The case of a 56-year-old acromegalic man with cervical lymphatic and spinal metastases from a primary pituitary carcinoma is described. Elevated basal levels of plasma growth hormone (GH) and insulin growth factor-1/Somatomedin C (IGF-1/SmC) were found. GH levels did not increase after TRH or LHRH administration but decreased after L-Dopa and glucose. Immunostaining of the metastatic tumor for GH and electron microscopy findings confirmed the diagnosis of pituitary GH-secreting carcinoma. Striking clinical improvement and a 46% decrease in plasma GH levels were observed with bromocriptine treatment, although IGF-1/SmC levels increased during therapy. The clinical course of most reported cases of pituitary adenocarcinoma has been one of progressive intracranial expansion of a pituitary neoplasm. In only 25% were metastatic lesions discovered antemortem, and disabling symptomatology caused by metastases was rare. Only four previously reported patients of 36 with pituitary carcinoma had acromegaly.
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PMID:Pituitary adenocarcinoma in an acromegalic patient: response to bromocriptine and pituitary testing: a review of the literature on 36 cases of pituitary carcinoma. 266 75

Twenty-two patients with metastatic cancer of the prostate were treated with ZoladexR, an LHRH analogue. In all cases plasma testosterone levels decreased to post-surgical castration values. This inhibitory effect of Zoladex on testicular steroid production had a favourable influence on the course of the malignancy, since 75 p. 100 of objective responses were obtained after 3 months of treatment. The functional symptoms were distinctly improved, and the drug was well tolerated, notably by the cardiovascular system. This immediate effectiveness seemed to last for several months, one-half of the patients still being in remission after 3 to 15 months. The beneficial effects of LHRH agonists, similar to those of pulpectomy or oestrogen therapy, are limited by the susceptibility of the tumour to hormones. In view of their effectiveness and good tolerance, LHRH agonists are useful in the management of advanced prostatic cancer, either as initial therapy or to replace a poorly tolerated oestrogen therapy. Further studies are needed to clarify their indications and the possible value of their association with anti-androgens or antimitotic drugs.
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PMID:[Value of a LHRH agonist (Zoladex) in hormonotherapy of advanced cancers of the prostate. Apropos of 22 patients]. 295 58

A stage D2 prostate cancer patient with biopsy-proven lung metastases and negative work-up for metastases is discussed. Treatment consisted of hormonal therapy in the form of chronic administration of an analog of gonadotropin-releasing hormone (GnRH-A), Buserelin, with follow-up for 24 months. The complete response of the patient to GnRH-A therapy provides an interesting and unusual case in the understanding of the biological behavior of prostate cancer.
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PMID:Complete response of lung metastases caused by prostatic cancer after chronic administration of a gonadotropin-releasing hormone analog, buserelin (HOE 766). 310 14

Buserelin (B) is a synthetic nonapeptide analogue of native LHRH. Upon continued administration it reliably lowers the serum testosterone level to less than 100 ng/dl. It has been used in a clinical trial for the treatment of patients with stage C, D1, and D2 prostate cancer. Analysis of efficacy of testosterone suppression and toxicity included all 207 buserelin-treated patients. A comparison with historical controls from two National Prostate Cancer Project (NPCP) studies considered only the 147 evaluable patients with distant metastases (stage D2). All patients received buserelin, 500 micrograms q 8 hours subcutaneously (s.c.) for the first 7 days and then elected to take 200 micrograms s.c. daily or 400 micrograms q 8 hours by the intranasal (i.n.) route. Seventy-three percent elected s.c. administration. Only 2% changed the route of administration. The serum testosterone (T) level increased during week 1 in both the s.c. (426 ng/dl) and the i.n. (521 ng/dl) group but reached castrate (less than 100 mg/dl) levels by 4 weeks in 90% of patients. Subsequently, the likelihood of having a T level greater than 100 was higher for those treated by the i.n. than the s.c. route. The mean T level 4 and 12 months after therapy for the s.c. treated patients was 29 and 28. These values were 61 and 53 for those taking i.n. buserelin. This difference may in part be due to poor compliance. Toxicity was minor. Twelve percent of 151 s.c. treated patients had at least one episode of reaction at the injection site. None required discontinuation of the agent. Seventy-two percent experienced hot flushes; this was the same for both the s.c. and i.n. groups. Only 2 of 207 patients had a severe exacerbation of symptoms (spinal cord compression) during the first week of therapy. The criteria for response to therapy were those of the NPCP. There was no significant difference in the percentage of patients achieving a response when comparing the B-treated D2 patients to the NPCP D2 patients treated with DES, 3 mg daily, or orchiectomy. More of the B-treated patients entered with pain, a poor performance status, and weight loss than the DES/orchiectomy group. Nonetheless, the progression-free survival did not differ among the treatments. In summary, buserelin reliably lowers the serum T level by week 4 in 95% of men. Treatment efficacy is equivalent to a historical group treated with either DES or orchiectomy.
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PMID:Efficacy of buserelin in advanced prostate cancer and comparison with historical controls. 313 44

Sixty-seven previously untreated patients presenting with clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average duration of treatment of 23.5 months. Only five patients have so far shown treatment failure with 91.8% of the patients still in remission at 2 years. Three patients have died from prostate cancer while three have died from other causes, 93.5% of the patients being alive at 2 years. Local control was achieved rapidly in all except one patient. Urinary obstruction and hydronephrosis were corrected in all cases. When comparing to recent data obtained after single endocrine therapy (orchiectomy or estrogens), or radiotherapy, the rate of treatment failure at 2 years is 3.5-fold lower after combination therapy (8.2%) than monotherapy (28.4%). The death rate at 2 years following start of the combination therapy is 6.5% while it is on average 22.2% (3.4-fold higher) in the studies using monotherapy (orchiectomy or estrogens) or radiotherapy. The present data suggest that treatment of prostate cancer with combination therapy before clinical evidence of dissemination of the disease permits a better response which is possibly explained, at least in part, by the lower degree of dedifferentiation and heterogeneity of the tumors.
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PMID:Combination therapy with flutamide and [D-Trp6]LHRH ethylamide for stage C prostatic carcinoma. 328 45

In 1941, Huggins and his colleagues discovered that testicular androgens exert a stimulatory effect on prostate cancer growth. Our group has made the key observations that the human adrenals, in addition to the tests, also secrete important amounts of androgens and cancer cells exhibit a marked heterogeneity of androgen sensitivity. In fact, human adrenals secrete large amounts of precursor steroids that are converted into active androgens in peripheral tissues (including the prostate), thus providing 40% to 50% of total androgens in adult men. The action of these androgens remaining after castration can be inhibited in prostatic cancer tissue by administering a pure antiandrogen that also decreases the local concentration of dihydrotestosterone (DHT). The castration levels of serum testosterone left in men after castration have an important stimulatory activity on the growth of androgen-sensitive normal as well as cancer tissues. Cancer cells have markedly different requirements for androgens. Some cell clones can grow in the presence of minimal amounts of androgens, requiring more complete androgen blockade and more potent antiandrogens for inhibiting growth. Among the compounds recommended as antiandrogens, the most unexpected finding is that many of them are devoid of any antiandrogenic activity. In fact, medroxyprogesterone acetate, chlormadinone acetate, and megestrol acetate have androgenic activity, but do not inhibit the peripheral action of DHT in prostatic tissue. These compounds should not be classified as antiandrogens. Cyproterone acetate, on the other hand, is a mixed agonist-antagonist. The only compounds showing pure antiandrogenic activity are Flutamide and its analogues. There is thus a need for a more complete blockade of androgens of both testicular and adrenal origins in order to exert a maximal inhibitory effect on cancer growth. We have therefore performed clinical studies in previously untreated stage D2 and C prostate cancer patients with the combination therapy using the LHRH agonist [D-Trp6, des Gly NH2(10)] LHRH ethylamide and the antiandrogen Flutamide. There was a significant increase in patients with a complete response, as compared with studies limited to the removal or blockade of testicular androgens. There was also a significant decrease in the number of non-responders, an increased duration of positive response, and a decrease in the death rate. This was achieved with minimal or no side effects, thus preserving a good quality of life.
Cancer Metastasis Rev 1987
PMID:Combination therapy in stage C and D prostatic cancer: rationale and five year clinical experience. 332 35

A significant number of patients with newly diagnosed prostatic cancer will be found to have metastatic disease at time of presentation. Since the work of Huggins and Hodges in the early 1940s, endocrine manipulation and androgen deprivation have become the accepted methods of treating this group of patients. Approximately 70 per cent to 80 per cent of patients demonstrate positive clinical response. Many experience a decrease in the size of the primary tumor, a decrease in the levels of serum acid phosphatase, relief of bone pain, a decrease in bladder outlet obstruction, an increase in appetite, and a generalized improvement in their overall sense of well-being. Adequate hormonal therapy usually consists of estrogen administration of bilateral orchiectomy, but other modalities include administration of antiandrogens, progestational agents, androgen-synthesis inhibitors, and, recently, gonadotropin-releasing hormone analogues. This latter group may have increasing applications, particularly if the evidence indicating reduced side effects continues to be substantiated. The probability of producing a positive clinical response is increased when hormonal therapy is introduced at the time of diagnosis, at which point the tumor is still likely to be androgen dependent.
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PMID:Hormonal therapy in prostatic carcinoma. 638 92

Treatment with an LHRH agonist (HOE-766) alone causes an almost complete blockage of testicular testosterone formation in rat and man. In order to neutralize androgens of adrenal origin, a pure antiandrogen (RU-23908) was given in combination with the LHRH agonist in the rat. At doses where each drug has no or minimal effect alone, prostate and seminal vesicle weight were reduced to 9 and 15% of control after 5 months of combined treatment, respectively. Among the species studied, man is the most sensitive to the inhibitory effect of treatment with LHRH agonists on testicular steroidogenesis. Near castration levels of serum testosterone and 5 alpha-dihydrotestosterone are obtained within 1-2 weeks of daily subcutaneous administration of the LHRH agonist [D-Ser(tbu)6, des-Gly-NH2(10)]LHRH ethylamide (HOE-766) in adult men with cancer of prostate. The decrease in serum androgen levels is accompanied by objective remission of the cancer in approximately 75% of cases. In a preliminary study where the LHRH agonist was administered in combination with the pure antiandrogen RU-23908, it was shown that the antiandrogen does not interfere with the LHRH-induced inhibition of serum androgen levels. The ease of application of this new form of hormonal therapy should permit its use at early stages of the disease and thus reduce the development of metastases and androgen-resistant cell clones.
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PMID:New hormonal therapy in prostate cancer: combined use of a pure antiandrogen and an LHRH agonist. 641 78

At doses which have no or minimal inhibitory effect when administered alone, the LHRH agonist [D-Ser(TBU)6,des-Gly-NH10(2)] LHRH ethylamide (HOE-766) and the antiandrogen RU-23908 administered simultaneously cause a marked inhibition of ventral prostate and seminal vesicle weight after 5 months of treatment. The effect of the LHRH agonist is due to a blockage of the testicular steroidogenic pathway. The same LHRH agonist administered to adult men with cancer of the prostate causes a marked inhibition of serum testosterone and dihydrotestosterone to castration levels within 1-2 weeks. Administration of the pure antiandrogen to men with cancer of the prostate already receiving the LHRH agonist does not interfere with the LHRH agonist-induced blockage of androgen biosynthesis: Moreover, objective signs of remission of the disease were rapidly observed in 8 out of 10 patients. The ease of application of this new form of hormonal therapy which neutralizes androgens from all sources should facilitate its early administration and thus minimize the development of metastases and androgen-resistant cell clones.
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PMID:New hormonal treatment in cancer of the prostate: combined administration of an LHRH agonist and an antiandrogen. 641 95

Twenty-two patients with advanced prostatic carcinoma were subjected either to orchiectomy (group I, n = 5) or to chronic administration of a gonadotropin releasing hormone agonistic analogue D, Ser (TBU)6, des Gly-NH2(10) LHRH nonapeptide (HOE 766) (group 2, n = 17). Plasma testosterone was similar in both groups prior to treatment (group 1: 636 +/- 129.29, group 2: 580.85 +/- 37.57; X +/- SE). The levels attained in group I were significantly lower (P less than .05) than those of group 2 through eight weeks of follow-up but were similar by the third month. Prostatic size (cm2) as estimated by transabdominal ultrasonography did not differ between the two groups prior to treatment (group 1: 23.6 +/- 3.35, group 2: 21.4 +/- 1.97; X +/- SE). Both therapies resulted in a decrease of prostatic size that was significantly more pronounced (P less than .05) in group I compared with group 2 by the first and third month; by the six month, there was no statistical difference in the prostatic size attained with either therapeutic modality. Persistent suppression of prostatic size was documented in all patients of group 2 chronically (up to 24 months) treated with HOE 766 even when there was evidence of uninhibited or progressive bony metastases. The above data 1) indicate the efficacy of the HOE 766 in inducing medical castration and prostatic shrinkage in advanced carcinoma of the prostate, 2) document the usefulness of transabdominal ultrasound in the follow-up of such patients, and 3) suggest a relationship between the rapidity of tumor shrinkage and Leydig cell suppression.
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PMID:Transabdominal ultrasonography in the evaluation of patients with advanced prostatic carcinoma: effects of castration and of chronic administration of a gonadotropin releasing hormone agonistic analogue. 641 31


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