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)

Recent studies have demonstrated that nitroso chemical carcinogens activate guanylate cyclase (EC 4.6.1.2) which catalyzes the production of guanosine 3',5'-monophosphate. This nucleotide is thought to be involved in normal and abnormal cell growth. We examined the effect of 3 major classes of anticancer chemotherapeutic agents, the antimetabolites (methotrexate and 6-mercaptopurine), antitumor antibiotics (adriamycin and actinomycin D), and alkylating agents (cytoxan, uracil mustard, isophosphamide, chlornaphazine, and 1-propranol-3,3'-iminodimethane sulfonate) on the activation of guanylate cyclase by nitroso chemical carcinogens. The anticancer chemotherapeutic agents noncompetitively blocked the activation of rat hepatic guanylate cyclase by N'-nitro-N-nitroso-N-propylguanidine (NNPG) and hydrazine. Adriamycin, methotrexate, and uracil mustard were the most effective inhibitors completely abolishing the effect of 1 mM NNPG on guanylate cyclase activity. The remainder of the anticancer chemotherapeutic agents abolished the NNPG activation of guanylate cyclase 40--70%. Since a previously described guanylate cyclase inhibitor has been shown to terminate the growth of an undifferentiated prostatic cancer in tissue culture the present data may indicate that one of the mechanisms by which anticancer chemotherapeutic agents exert their effects is by inhibition of tumor guanylate cyclase activity.
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PMID:Inhibition of nitroso chemical carcinogen activation of rat hepatic guanylate cyclase by anticancer agents. 3 20

Twenty-seven patients with a diagnosis of metastatic adenocarcinoma of the prostate were treated in a randomized, prospective trial with either Cyclophosphamide or a combination of Adriamycin, 5-Fluorouracil, and Cyclophosphamide. Doses were either Cyclophosphamide alone (800-1200 mg/m2 iv q 3 weeks) or Cyclophosphamide (150-200 mg/m2 po Day 3-6) plus 5-FU (400-500 mg/m2 iv Day 1, 8) plus Adriamycin (30-50 mg/m2 iv Day 1) given as a 4 week treatment cycle. Patients with compromised bone marrow reserve initially received the lower dose level. Objectively stable disease as defined by a modification of the National Prostatic Cancer Project criteria was seen in 53% of the 15 Cyclophosphamide treated patients and in 50% of the 12 combination treated patients. Survival was not significantly different in the two arms. However, the survival of patients responding to Cyclophosphamide was significantly longer than that of patients responding to the combination (median 18.6 months versus 8.1 months, p less than 0.05). Gastrointestinal and hematologic toxicity was moderate with both regimens. Therefore, in the present study, Cyclophosphamide alone was as effective as the combination of Cyclophosphamide, 5-FU and Adriamycin for patients with disseminated prostatic carcinoma. The moderate hematologic toxicity noted with both regimens suggests further evaluation of drug combinations utilizing higher dosages of active agents in this disease.
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PMID:Cyclophosphamide (NSC 26271) versus the combination of adriamycin (NSC 123127), 5-fluorouracil (NSC 19893), and cyclophosphamide in the treatment of metastatic prostatic cancer: a randomized trial. 36 13

Results of disease-oriented phase II trials with cis-dichlorodiammineplatinum(II) (cis-platinum) in 135 adequately treated patients with advanced urothelial tumors at Memorial Sloan-Kettering Cancer Center are presented. In four protocols which used cis-platinum alone or in combination with Adriamycin and/or cyclophosphamide in 95 patients with bladder cancer, no significant difference (46%--54%) in the number of partial remissions (PRs) in previously untreated patients was noted. The median duration of response in three of the four protocols was 5--7 months. A review of the literature indicates that cis-platinum used singly produced remissions in 45% of 67 patients (95% confidence limit, 12%--57%). In the treatment of superficial bladder tumors, intravesically administered cis-platinum induced few complete or sustained remissions. The difficulties in evaluating response with intravesical therapy are discussed. The importance of patient selection, particularly the need to include patients with objectively measurable disease parameters, in phase II trials is stressed. Differences in patient characteristics and response criteria will necessitate prospective randomized trials of cis-platinum alone versus cis-platinum combination regimens in the treatment of metastatic disease. cis-Platinum was inactive (12% PRs) in 25 patients with prostatic cancer who had objectively measurable parameters. It is of interest that PRs were obtained in three of six patients (50%) with penile cancer. A review of the literature and the data in the present series indicates that cis-platinum has no value in the treatment of metastatic hypernephroma.
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PMID:Phase II trials with cis-dichlorodiammineplatinum(II) in the treatment of urothelial cancer. 38 26

A number of therapeutic agents including L-asparaginase, Actinomycin-D, CCNU, Hydroxyurea, 5-FU, Cis-platinum, Cyclophosphamide, orchiectomy, Adriamycin and DES alone and in various combinations has been applied against the Dunning R-3327 rat prostatic adenocarcinoma subline G. We have found a parallel between the results of this study and those of similar therapeutic application to the human tumor. We conclude that this animal model may prove to be a useful screening system for agents against human prostatic cancer.
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PMID:Chemotherapy of the transplantable adenocarcinoma (R-3327) of the Copenhagen rat. 91 40

Adriamycin and the other anthracyclines are amongst the most effective cytotoxic agents at the clinician's disposal. At least one of the reasons for their efficacy is the large number of mechanisms by which they can induce potentially lethal damage in a dividing malignant cell. Adriamycin and epirubicin are amongst the more effective agents in advanced hormone-independent prostate cancer. When given in full doses, they produce a reasonable number of objective as well as subjective responses, but the resultant toxicity precludes their use at high dose in many patients. In a number of well-documented studies, lower doses of these agents have yielded useful subjective responses with minimal toxicity.
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PMID:The use of adriamycin and its derivatives in the treatment of prostatic cancer. 139 27

One hundred eleven patients with endocrine-refractory Stage D prostate cancer were treated with weekly administration of 20 mg/m2 body surface area of doxorubicin hydrochloride (Adriamycin). Fifty-seven were part of a randomized study comparing doxorubicin and prednisone to prednisone alone. There were significantly more subjective responders in the doxorubicin group than in the prednisone group (p less than 0.01). The number of patients with evidence of stable disease was also higher during the chemotherapy arm compared with prednisone alone (p = 0.02). Patients taking doxorubicin had a slightly longer period of stable disease than did those taking prednisone (p = 0.08). Overall survival, however, was not prolonged (p = 0.26). Fifty-four patients took part in an open trial and 69 percent responded to treatment. All of these had clinical improvement. Side effects were minimal with cardiotoxicity noted in less than 15 percent among patients with side effects. Over 35 percent had no side effects. Thus single agent, weekly doxorubicin therapy as evaluated in our experience, while well tolerated and of subjective benefit, does not provide the patient with a significant longer progression-free survival or improved overall survival.
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PMID:Experience with weekly doxorubicin (adriamycin) in hormone-refractory stage D2 prostate cancer. 161 14

Cytotoxic chemotherapy has not provided survival benefit in metastatic prostate cancer, although it has been used most frequently in patients with far-advanced, refractory disease. To evaluate the effects of chemotherapy given earlier in the course of the disease, the Southwest Oncology Group (SWOG) performed a randomized trial between September 1982 and October 1986 comparing endocrine therapy (diethylstilbestrol [DES] or orchiectomy) alone followed by cyclophosphamide-Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy at progression versus initial combined chemo-endocrine therapy. One hundred forty-three patients were registered, and only six were declared ineligible. Patients on the combined chemo-endocrine therapy arm had a slightly higher response rate (63%) compared with endocrine therapy alone (48%). A log-linear model of tumor response and treatment arm adjusted for the stratification factors favored the combination arm (P = .059). Only three of 27 patients on the endocrine therapy alone arm had an objective partial response when crossed over to chemotherapy, while two others had stable disease. Despite the difference in initial response rate, time to treatment failure and survival were identical in the two treatment arms. Seventy-seven percent of patients on the initial endocrine therapy alone arm have died (median survival, 25.6 months) compared with 78% on the chemo-endocrine therapy arm (median survival, 22.0 months). No significant effect of treatment on survival was observed even after adjustment for the stratification variables in a Cox regression model. Exploratory survival analyses with patients on both arms combined did show a marginally significant time to treatment failure and survival advantage for patients treated with DES rather than orchiectomy as initial endocrine therapy. Eighty-six percent of patients treated by orchiectomy have died compared with only 65% of those treated with DES. These data do not support the addition of cytotoxic chemotherapy to initial endocrine therapy in patients with metastatic prostate cancer.
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PMID:Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study. 221 4

Analysis of the results of chemotherapy in patients with carcinoma of unknown primary site is complicated by the small sizes of most treatment series and patient heterogeneity. Careful evaluation of clinical and pathologic information may identify patients with a relatively high likelihood of response to systemic therapy. This includes patients in whom immunohistochemical studies or electron microscopy, or both, suggest a likely tumor type responsive to systemic therapy, such as prostate cancer, lymphoma, or a neuroendocrine tumor. Clinical evaluation can also identify potentially responsive patients, particularly those with clinical features in common with the extragonadal germ cell tumor syndrome. For patients who do not fit into these more treatable categories, most combination chemotherapy programs have response rates of less than 30% and median survivals of less than one year. Randomized trials have not established any clearly superior chemotherapy program. Regimens containing both Adriamycin (doxorubicin) and mitomycin-C produce response rates of approximately 25% but are associated with the possibility of severe hematologic toxicity, and rarely a syndrome resembling the hemolytic-uremic syndrome. The choice between chemotherapy and supportive care only must be individualized, and the latter option is appropriate for many patients. More detailed clinical and pathologic analyses in conjunction with clinical trials, particularly employing newer diagnostic techniques, are vital to provide better prospective data from which to identify relevant clinical subsets that allow an estimate of an individual patient's likelihood of response and the suitability of systemic chemotherapy.
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PMID:Empiric chemotherapy in patients with carcinoma of unknown primary site. 240 56

Weekly intravenous doses of 20 mg Adriamycin were given to 22 patients with hormone-resistant metastatic cancer of the prostate. (Median duration treatment: 8 weeks; range 3-60 weeks.) Of 21 adequately treated patients, 6 achieved a subjective response (Median duration: 4 weeks; range 4-28 weeks). In 2 patients a more than 50% size reduction of measurable lymph node metastases was observed, while the disease progressed at other sites (mixed response). The median survival from treatment start (8.5 months) was unrelated to the achievement of subjective response. In 10 of 21 patients a reduction of serum alkaline phosphatase was observed and 7 of 21 patients showed a decrease of serum prostatic acid phosphatase. These biochemical changes were not related to response. Toxicity was generally mild, but one case with severe irreversible thrombocytopenia was observed after 3 weekly doses of 20 mg Adriamycin. Weekly low-dose Adriamycin has marginal subjective efficacy in progressing hormone resistant prostatic cancer, a condition where effective and feasible chemotherapy is lacking. The combination of weekly low-dose Adriamycin with other agents, preferably hormones, should be explored.
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PMID:Weekly low-dose adriamycin in hormone-resistant metastatic cancer of the prostate. 243 53

From 1982 to 1985, the National Prostatic Cancer Treatment Group conducted a randomized prospective trial of single-agent or combination chemotherapy in 180 patients with metastatic prostatic disease refractory to hormonal therapy. All three of the treatment regimens, methotrexate, Adriamycin plus cyclophosphamide, cis-platinum plus 5-fluorouracil plus cyclophosphamide, showed similar survival and progression-free survival intervals. Future studies utilizing these or other agents, in similar or modified dosage schedules or delivery mechanisms, should note these results. Protocols designed to address subjective quality of life measures and other benefit ratios can be effectively employed considering this report.
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PMID:Hormone-refractory metastatic prostatic cancer treated with methotrexate, cyclophosphamide plus adriamycin, cis-platinum plus 5-fluorouracil plus cyclophosphamide. National Prostatic Cancer Project randomized trial. 329 71


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