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)

Ischemic colitis is an infrequent but potentially devastating complication of abdominal aortic reconstruction. Identification of patients with predisposing risk factors for the development of ischemic colitis can guide intraoperative measures to preserve or restore colonic blood flow during aortic surgery. Previous radiation therapy for pelvic malignancy may be one such predisposing risk factor. Two cases are presented in which ischemic colitis complicated abdominal aortic reconstruction in the setting of previous pelvic irradiation. In the months after radiation therapy for prostate cancer, one patient underwent infrarenal abdominal aortic aneurysm repair. Ischemic infarction of the sigmoid colon developed acutely after surgery and required emergent sigmoid colectomy. The second patient underwent reconstruction of an infrarenal abdominal aortic aneurysm after having had radiation therapy for a bladder tumor. Despite an initial satisfactory result, the patient's abdominal pain and diarrhea progressively worsened and he eventually required sigmoid colectomy for severe ischemic colitis. In both of these patients, the inferior mesenteric arteries were patent and had not been reimplanted. The association of pelvic radiation therapy with ischemic colitis after aortic reconstruction should focus attention to the operative details for maintaining the colonic circulation in these patients. Reimplantation of the inferior mesenteric artery in particular may prevent both the acute and the insidious variants of this complication in patients who undergo aortic surgery and decrease the incidence of this complication in patients with a history of radiation therapy to the pelvis.
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PMID:Pelvic radiation therapy as a risk factor for ischemic colitis complicating abdominal aortic reconstruction. 862 9

Casodex (bicalutamide, Zeneca Limited) is a nonsteroidal competitive inhibitor of androgens at the androgen receptor. The drug was developed to fulfil a number of needs for the treatment of prostate cancer. The specific aim was to demonstrate pharmacological activity, which would translate into clinical efficacy, good tolerability in the context of its use, oral availability, a convenient and forgiving dosing regimen, and clinical acceptability. Casodex has been shown to be orally bioavailable and well absorbed, with a plasma half-life of around 1 week. Although steady-state levels are not reached for 1 month, there is evidence that the androgen receptor blockade achieved with Casodex is equivalent to that of flutamide by the end of the first day. The dose of Casodex was established in a series of dose-ranging studies using the surrogate endpoints of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA). Initial studies suggested that a dose of 50 mg daily gave a fall in PAP equivalent to that seen with castration. This dose was, therefore, evaluated as monotherapy and subsequently as a component of combined androgen blockade. Higher doses were evaluated using PSA as a surrogate endpoint and, although doses up to 450 mg have been given to man, 150 mg daily is well tolerated with demonstrable evidence of activity. Although trials of the drug at 150 mg in monotherapy have, to date, not shown survival equivalence with castration, Casodex has been well tolerated with evidence of good symptomatic response and quality-of-life benefits including the potential of retaining libido. In combination treatment, Casodex is associated with significantly less gastrointestinal effects (diarrhoea) than the nonsteroidal antiandrogen flutamide (Eulexin, Schering-Plough International). Casodex is not associated with alcohol intolerance, pneumonitis and ocular defects which have been seen with the antiandrogen nilutamide (Anandron, Roussel). Moreover, since Casodex is a nonsteroidal antiandrogen, no steroidal effects have been seen.
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PMID:Clinical progress with a new antiandrogen, Casodex (bicalutamide). 871 70

Between January 1992 and September 1993, 813 patients with stage D2 prostate cancer were enrolled in a multicentre, double-blind (for antiandrogen therapy) trial and randomised to antiandrogen therapy with Casodex (bicalutamide, 50 mg once daily) or flutamide (250 mg three times daily) and to luteinising hormone-releasing hormone (LHRH) analogue therapy with Zoladex (goserelin, 3.6 mg every 28 days) or leuprolide (7.5 mg every 28 days). Time to treatment failure was the primary efficacy endpoint. At a median follow-up time of 49 weeks, there was a significant (p = 0.005) difference between groups in time to treatment failure in favour of Casodex plus LHRH analogue. Overall, 168 (42%) of 404 patients in the Casodex plus LHRH analogue group and 218 (53%) of 409 patients in the flutamide plus LHRH analogue group reached a treatment failure endpoint. Although a cause-specific treatment-failure analysis was not performed, the difference between groups in treatment failure attributed to adverse events (mainly diarrhoea) was evident primarily in the first 7 months of therapy. The difference between groups in treatment failure for objective progression was most evident after 1 year of therapy. With further follow-up (median time of 95 weeks), the result for time to treatment failure, although no longer statistically significant, were consistent with the previous finding of an improvement in time to treatment failure associated with Casodex plus LHRH analogue therapy. With a median of 95 weeks of follow-up, 34% of deaths had occurred. The survival analysis was not dissimilar between the 2 groups. At 49 weeks median follow up, the incidence of diarrhoea was significantly (p < 0.001) lower among patients in the Casodex plus LHRH analogue group. Diarrhoea led to withdrawal from therapy for 2 patients in the Casodex plus LHRH analogue group, compared with 25 patients in the flutamide plus LHRH analogue group. In conclusion, Casodex plus LHRH analogue is well tolerated and effective with an improvement in time to treatment failure over flutamide plus LHRH analogue. Survival was not dissimilar between the 2 treatment groups.
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PMID:A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. 871 71

Maximum androgen blockade, a relatively recent development in the treatment of prostate cancer, combines medical or surgical castration with antiandrogen therapy. A large randomized study comparing the non-steroidal antiandrogen, bicalutamide, with flutamide, each in combination with luteinizing hormone-releasing hormone (LHRH) analogs, showed that after a median follow-up of 49 weeks, the time to treatment failure was significantly longer for the bicalutamide patients compared with the flutamide patients (p = 0.005). After a median follow up to 95 weeks, bicalutamide in combination with LHRH analog therapy produced at least equivalent efficacy with flutamide in combination with LHRH analog therapy in terms of time to treatment failure and equivalent efficacy in terms of survival. The tolerability profile of bicalutamide, as based on reported findings and a literature review, indicates a superior tolerability to that of currently available antiandrogens, particularly with respect to diarrhea with a low incidence of treatment-related withdrawals.
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PMID:Bicalutamide: a new antiandrogen for use in combination with castration for patients with advanced prostate cancer. 874 95

Androgen deprivation based on hormone manipulation is the treatment of choice in advanced prostatic cancer. The unequivocal role of adrenal androgens in the growth of prostatic cancer after medical or surgical castration requires a new logical approach (complete androgen blockade) in the treatment of advanced prostate cancer. One hundred and fifty patients with biopsy-proven advanced prostatic cancer were randomized into two groups. One group (74 patients) received leuprolide + flutamide (complete androgen blockade); the second group (76 patients) received only leuprolide and, during the first 3 weeks of treatment, cyproterone acetate (150 mg/day) to prevent flare-up phenomena. The aim of the study was to evaluate the differences between the two groups on overall survival and time to progression (log-rank test). One hundred and twenty-five patients were evaluable, 62 in the leuprolide-only group and 63 in the leuprolide + flutamide group. Median duration of follow-up was 102 weeks. No statistical difference between the two groups was observed in overall survival, in time to disease progression, and in time to treatment failure. In the combination (leuprolide + flutamide) treatment group, a positive trend for overall survival and in time to progression was observed in a subgroup of patients with good performance status and no bone metastases. We observed mild gastrointestinal toxicity (diarrhea, nausea) in the group treated with leuprolide + flutamide. The aim of this study was to compare the effectiveness of total androgen withdrawal with medical testicular suppression in advanced prostatic cancer. No significant statistical difference was observed between the two groups in overall survival and in time to progression, but probably too few patients were enrolled in each treatment arm to give a statistical interpretation of our results. We conclude that there is a positive trend in the combination treatment arm in patients with good prognostic factors.
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PMID:Combination treatment versus LHRH alone in advanced prostatic cancer. 877 12

Casodex (bicalutamide, Zeneca Ltd), has been developed for prostate cancer therapy. Its preclinical, pharmacokinetic, pharmacodynamic, clinical efficacy and tolerability data are described. Casodex is a potent and specific non-steroidal antiandrogen. Clinical studies indicated that Casodex is orally bioavailable and well absorbed, with a plasma half-life of around 1 week. A Casodex dose of 50 mg daily decreased prostatic acid phosphatase comparable with castration. This dose was, therefore, evaluated initially as monotherapy and later as a component of maximal androgen blockade. Using prostate specific antigen as an end point, Casodex 150 mg daily was well-tolerated with demonstrable evidence of activity. Casodex 150 mg monotherapy was less effective than castration in terms of efficacy in patients with metastatic disease at entry. However, in patients non-metastatic at entry, Casodex 150 mg monotherapy appeared to be equivalent to castration in terms of time to death (data immature). Casodex was well-tolerated. In combination treatment, Casodex at 50 mg daily was at least as effective as 750 mg flutamide (Eulexin, Schering-Plough International) with respect to time to treatment failure, equivalent in terms of survival, and better tolerated with respect to diarrhoea. In conclusion, Casodex is a good option for the antiandrogen component of maximal androgen blockade.
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PMID:Casodex (bicalutamide): overview of a new antiandrogen developed for the treatment of prostate cancer. 907 8

Ketoconazole has been used with success to treat disseminated intravascular coagulation and acute spinal cord compression syndromes associated with metastatic prostatic adenocarcinoma. It effects prompt, reversible medical castration, making it especially useful as empiric therapy when histologic diagnosis is delayed but prostate cancer is suspected. Side effects are usually limited to asthenia, nausea, diarrhea, and gynecomastia, but a theoretical risk of adrenal suppression exists. We report a case of fulminant adrenal crisis precipitated by ketoconazole given on a 6-hour dosing schedule in a patient with nerve root compression secondary to prostatic metastases. Through a review of the literature, we attempt to provide a better understanding of the use and potential dangers associated with ketoconazole therapy.
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PMID:Ketoconazole-induced adrenal crisis in a patient with metastatic prostatic adenocarcinoma: case report and review of the literature. 914 92

From January, 1991, to December, 1995, forty-two patients with prostatic cancer (T2-T4: 40 patients) were treated with a luteinizing hormone-releasing hormone (LHRH) analog (2 administrations before and 3 during irradiation), Flutamide (1 month) and external beam radiation therapy (45 Gy to the whole pelvis and a 20 Gy boost). All patients completed the protocol and the LHRH analog was continued for 1-6 months in 5 patients with partial response at the end of radiotherapy. The incidence of acute toxicity was low according to the Radiation Therapy Oncology Group and European Organization for Research and Treatment in Cancer score (grades 1-2; 19% hematologic, 36% intestinal and 38% urological toxicity). At a median follow-up of 21 months (range: 1-60 months), one patient had local disease progression and lung metastases and two had bone metastases; the three relapsing patients were given the LHRH analog and exhibited partial response to rectal examination (1 case) and to bone scan (2 cases). Pain disappeared completely in both the patients with bone metastases. Overall 3-year survival and disease-free survival rates were 97% and 79%, respectively. Disease-free survival was significantly related to cT (at 3 years: cT2: 100%; cT3: 81.2%; log rank test: 0.0081). Late toxicity was observed in two patients: rectal bleeding in one case and chronic diarrhea in the other. The combined protocol used in this study was feasible and well tolerated. Our results seem to confirm the promising preliminary results of Radiation Therapy Oncology Group 8610 study.
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PMID:[Neoadjuvant combined hormonal therapy and radiotherapy with external beam irradiation in prostatic carcinoma]. 924 24

We present a patient with prostate cancer who developed symptomatic hypocalcemia while taking oral clodronate for painful bony metastases. He had a past history of a bowel resection for Crohn's disease, and, although he was normocalcemic prior to taking clodronate, it is likely that the surgery had caused mild hyperparathyroidism. The addition of clodronate prevented the chronic osteolysis of bony metastases, which would have helped maintain normocalcemia. The case was complicated by hypomagnesemia and hypokalemia resulting from diarrhea. Hypomagnesemia is a cause of refractory hypocalcemia and hypokalemia. This case illustrates two important points. First, care must be taken with bisphosphonates in patients with a previous bowel resection. Second, magnesium plays a key role in the metabolism of both calcium and potassium, and must be considered in the evaluation of the hypocalcemic patient.
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PMID:Symptomatic hypocalcemia with oral clodronate. 949 15

Castration or antiandrogen monotherapies remain options for prostate cancer treatment as only marginal benefits have been demonstrated with combined androgen blockade, although it may be that certain subgroups of patient may benefit. Of the nonsteroidal antiandrogens, bicalutamide 150 mg was as effective as castration in M0 patients with significant improvement in sexual interest and physical capacity, but the trial has yet to reach maturity. In M1 patients, bicalutamide 150 mg was not as effective as castration but this may be outweighed by symptomatic and quality of life benefits. Nilutamide is not recommended as monotherapy and there are little data on flutamide. The steroidal antiandrogen, cyproterone acetate, is as effective as oestrogen therapy and has a better side-effect profile, although cardiovascular and hepatic side effects are still of concern. Compared with flutamide, in a recently completed EORTC study, side effects such as gynaecomastia, diarrhoea, nausea, and liver function deterioration occurred less often, and thrombotic effects more often, in the cyproterone acetate group. No difference was seen in the preservation of sexual functioning. Quality of life issues are becoming increasingly important and thus antiandrogen monotherapy may become more widely used in the management of prostate cancer.
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PMID:Antiandrogens as monotherapy for prostate cancer. 985 90


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