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)

The efficacy of an association of cyclophosphamide (CPM) and 5-fluorouracil was studied in 15 patients with prostate cancer not responding to oestrogen therapy, and more particularly its effect on pain due to bone metastases. No objective improvement was noted with this association, but there was a definitite reduction in bone metastases pain in 5 of the patients, with an average remission time of 4 months. Half of the patients had nausea and vomiting, but in spite of this digestive intolerance those patients who obtained pain relief for 4 months considered the treatment to be of positive value. This therapy is recommended only fater the failure of castration, anti-androgens, and oestrogens, together with nitrogen mustard (Estracyt) and corticotherapy.
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PMID:[Palliative chemotherapy with 5 FU and CPM in cancer of the prostate with bone metastases resistant to oestrogens. A clinical trial (author's transl)]. 9 8

A multicenter cooperative study was conducted to evaluate the clinical efficacy and safety of cis-diammine(glycolato)platinum (254-S), a second-generation anticancer platinum complex, in the treatment of genitourinary cancers. 254-S was given i.v. at 100 mg/m2 at 4-week intervals. As a result, 2 complete responses (CRs) and 8 partial responses (PRs) were obtained in 35 patients with transitional-cell carcinoma (TCC) of the urinary bladder or pyeloureter, 3 PRs were obtained in 16 subjects with prostatic cancer, and 6 CRs and 6 PRs were obtained in 15 patients with testicular cancer, generating objective response rates of 28.6% [95% confidence interval (CI), 14.6%-46.3%], 18.8% (95% CI, 4.0%-45.6%), and 80.0% (95% CI, 51.9%-95.7%), respectively. Bone marrow suppression was the dose-limiting toxicity, although it was reversible. Although no hydration was performed in approx. 40% of the patients, the incidence of nephrotoxic effects was low and most of those encountered were mild, the exception being one patient who showed severe renal insufficiency after the first treatment. Nausea and vomiting occurred in approx. 70% of the patients, but most gastrointestinal toxicities were controlled without antiemetic treatment. In addition, liver-function impairment was rarely observed. We conclude that 254-S is a promising cisplatin analogue for the treatment of genitourinary cancers and is worthy of further investigation in large-scale, randomized comparative studies with other platinum derivatives in both single-agent and combination regimens.
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PMID:Phase II study of cis-diammine(glycolato)platinum, 254-S, in patients with advanced germ-cell testicular cancer, prostatic cancer, and transitional-cell carcinoma of the urinary tract. 254-S Urological Cancer Study Group. 133 48

Between September 1982 and May 1984, combination chemotherapy with cis-platinum, peplomycin and adriamycin was administered to 12 patients with histologically confirmed adenocarcinoma of the prostate and progressive disease with evaluable parameters. Cis-platinum (CDDP) 20 mg/sqm was administered intravenously on Days 1-5, peplomycin 5 mg/sqm by 24-hour continuous drip infusion on day 1-5 and adriamycin 25 mg/sqm on Day 1. This course was repeated every 28 days. The dose and schedule were modified by hematologic toxicity or other side effects. One patient refused therapy because of severe nausea and vomiting; therefore 11 patients were eligible for response evaluation. Of the 11 patients, two had a documented PR, five had SD and four had PD. Ten patients whose disease eventually progressed received a second line of therapy consisting either of estramustine or estrogen. Of these ten patients, 6 had a documented PR, one had SD and three had PD. It is concluded that this combination chemotherapy regimen may prime advanced prostatic cancer to respond to hormonal therapy, even though it has only a limited effect on advanced prostatic cancer.
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PMID:[A trial of combination chemotherapy. Cis-platinum, peplomycin and adriamycin for advanced prostatic cancer]. 170 Jan 77

From November 1984 to April 1989, 40 patients with advanced prostate cancer were treated with chemohormonal therapy consisting of orchiectomy, diethylstilbestrol diphosphate, CDDP and cyclophosphamide. Of the 40 patients, 23 had partial response, 15 had stable disease and 2 had progression of disease at 3 months after the initiation of the treatment. In analysis of survival rate, the 5-year survival rate of all cases was 61.5%. The prognosis of the patients with low grade tumors was better than those with high grade tumors. In stages C and D patients, the survival rate was 75%, and 56%, respectively. Relapse occurred in 5 patients. The interval between start of treatment and relapse was approximately 20 months. Relapse rate was lower than that of 23 patients treated with hormonal treatment alone during the same periods (p less than 0.05). Gastrointestinal symptoms including different degrees of nausea and vomiting were observed in about half of the patients. Myelosuppression was seen in a few cases. These findings suggest the effectiveness of chemohormonal therapy for newly diagnosed advanced prostate cancer.
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PMID:[Treatment results of combined hormone and chemotherapy in patients with advanced prostate cancer]. 195 24

Forty-seven patients with solid tumors were treated on a phase I study of menogaril administered by mouth once per week. Nausea and vomiting were excessive at weekly doses of 350 and 450 mg/m2/week but were tolerable and controlled reasonably well by antiemetics at lower doses. There appeared to be a relatively shallow dose-vs-granulocytopenia curve above a menogaril dose of 180 mg/m2/week. No patient receiving chronic dexamethasone for cerebral edema developed granulocytopenia, even at menogaril doses of 350-450 mg/m2/week. Two patients developed neutropenic infection. No patient developed thrombocytopenia. Mild arrhythmias were seen in 3 patients. Two patients suffered possible myocardial infarcts that may not have been related to treatment. Asymptomatic blood pressure fluctuations were common and were probably not related to treatment. Diarrhea was dose-related but was generally not severe. Alopecia and stomatitis occurred occasionally. Minor responses were seen in two patients with gliomas, and three of five evaluable prostate cancer patients experienced marked pain relief. The dose recommended for phase II studies is 250-300 mg/m2/week with antiemetic pretreatment. This schedule appears to allow an oral menogaril dose-intensity that is approximately double that attainable with other oral schedules that have been studied.
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PMID:Phase I study of oral menogaril administered on a once weekly schedule. 214 May 64

Flutamide is a nonsteroidal pure antiandrogen that acts by inhibiting the uptake and/or binding of dihydrotestosterone to the target cell receptor, thus interfering with androgen action. Flutamide is well absorbed orally and extensively metabolized; its active metabolite, 2-hydroxyflutamide, is formed rapidly and excreted almost entirely by the kidneys. Clinical studies in prostate cancer patients have demonstrated efficacy with flutamide monotherapy in patients who had received no prior treatment, in untreated patients with combined androgen blockade concomitantly with a luteinizing hormone-releasing hormone (LHRH)-agonist, and in relapsed patients. A randomized, placebo-controlled trial demonstrated a 26 percent increase in median survival for patients treated with leuprolide plus flutamide compared with leuprolide plus placebo. When given as monotherapy and in combination with an LHRH-agonist, flutamide is well tolerated. The usual adverse effects are gynecomastia and mild diarrhea when given as a single agent. In combination with an LHRH-agonist, hot flashes, loss of libido, impotence, mild nausea and vomiting, gynecomastia, and diarrhea are commonly reported. However, only diarrhea occurred more frequently in patients treated with leuprolide plus flutamide than in those treated with leuprolide plus placebo. Flutamide is indicated in combination with an LHRH-agonist (e.g., leuprolide) as initial therapy in metastatic (stage D2) prostate cancer. The usual dose is 250 mg po tid given at eight-hour intervals and started concurrently with the LHRH-agonist. Formulary addition is recommended.
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PMID:Flutamide: an antiandrogen for advanced prostate cancer. 219 61

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.
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PMID:High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects. 247 59

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.
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PMID:Phase I clinical investigation of amonafide. 254 5

From November 1981 to November 1987, 35 patients with newly diagnosed advanced prostatic cancer (6 Stage C cases and 29 Stage D2 cases) were treated by chemoendocrine therapy consisting of orchiectomy, diethylstilbestrol-diphosphate and cisplatin. Objective responses were assessed at 3 months after the start of treatment. Of the 35 patients, 8 had PR (partial response) and 27 was objective stable by NPCP criteria. Objective progression was not seen. In analysis of long-term results, the 3-year and 5-year survival rate for total cases were 75.8% and 60.7%, respectively. For Stage C cases, the 3-year and 5-year survival rates were 100% and 100%; for Stage D2 cases, they were 72.2% and 54.2%, respectively. Relapse was seen in 7 (24.1%) of the 29 Stage D2 cases. All of these 7 patients had poorly differentiated adenocarcinoma and most of them had more than 10 bone metastases. As for side-effects, gastroenteric symptoms (nausea and vomiting), anemia and slight liver dysfunction were seen. These results suggest that the chemoendocrine therapy is an effective treatment in newly diagnosed cases of advanced prostatic cancer.
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PMID:[Chemoendocrine therapy of newly diagnosed advanced prostatic cancer]. 272 44

Carboplatin was evaluated in a phase II study involving 109 patients with genitourinary cancer. A total of 21 cases of advanced testicular tumor, 38 of transitional cell carcinoma (TCC) of the urinary tract and 25 of prostatic cancer were evaluable for response. The response rate in testicular tumors was 48%, with 70% in seminomas and 27% in nonseminomas. Three responses were observed in patients previously treated with cisplatin. In TCC, the response rate was 18%. No response was observed in prostatic cancer. Carboplatin was well tolerated with no significant renal impairment and ototoxicity detected. Nausea and vomiting were experienced by 50% of patients but the severity was low. Severe myelosuppression, thrombocytopenia and leukopenia were observed. In conclusion, carboplatin has demonstrated activity in both testicular tumors and TCC of the urinary tract and is worthy of further study, especially in combination with other active drugs.
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PMID:[Phase II study of carboplatin in genitourinary cancer. Urological Cooperative Study Group on Carboplatin]. 304 77


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