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)

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

A transplantable, metastasizing prostatic adenocarcinoma (Tumor I) in Lobund Wistar rats was examined for activity and distribution of five hydrolytic enzymes and for ability to accumulate radioactive zinc. The results suggest that the tumor had arisen in the ventral lobe of the prostate and that its growth was not affected by orchiectomy, adrenalectomy, or replacement treatment with exogenous androgen or corticosteroids. The androgen independency of the tumor was further shown by the low uptake of 3H-testosterone, in contrast to the high uptake in the ventral prostate. Tumor growth was retarded by Cytoxan but not by 5-fluorouracil, Estracyt, or streptozotocin, three agents clinically effective in the treatment of some patients with prostatic cancer resistant to endocrine therapy. It is concluded that this tumor in Lobund Wistar rats may be an adequate model for human prostatic cancers resistant to the agents mentioned above.
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PMID:A rat prostatic adenocarcinoma as a model for the human disease. 44 85

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

The response and duration of survival were evaluated for patients with stage D relapsing prostatic cancer who were randomized to cyclophosphamide (Cytoxan),5-fluorouracil (5-FU) or standard therapy, or to subsequent chemotherapies. The chemotherapies on initial randomization were superior to the standard therapy in the number of responders and duration of response. Survival was longer for responders (stable or partial regression) on chemotherapy by comparison to responders (stable only) on standard therapy. The survival for patients receiving initial and crossover chemotherapy was significantly improved for patients who responded to therapy. Chemotherapy of advanced relapsing stage D prostatic cancer is more beneficially treated by specific chemotherapy as shown in this randomized study.
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PMID:The continued evaluation of the effects of chemotherapy in patients with advanced carcinoma of the prostate. 103 May 48

Fifteen years ago we embarked on a treatment protocol for prostatic cancer patients with widespread disease (Stage D2) which included both hormonotherapy (i.e., orchiectomy and diethylstilbestrol [DES] 5 mg/day--later substituted with cyproterone acetate [CPA] 0.2 g/day) and chemotherapy (cyclophosphamide and 5-fluorouracil 10 mg/kg/week). The rationale for such an approach was the universally poor results obtained from the conventional approach which advocated consecutive single-treatment schedules once the previous therapy had ceased to be effective. As such a conventional approach probably allowed the selection of new resistant cell clones, we assumed that perhaps an aggressive combined systemic therapeutic approach from the start, would give such a group of patients--already with generalized disease--a better long-term result. In retrospect, after fifteen years, the chemotherapy on a series of 50 patients so treated has been well tolerated with only minimal, temporary side effects. This regimen was continued up to five years with a reduced maintenance dose. The hormonotherapy was also well tolerated, and was fully maintained. Only 28 percent died of their disease (16% within the first 2 years); 28 percent died of other causes; 40 percent are still alive (14% with clinical disease). In only 9 cases was the chemotherapy discontinued for various reasons. No control arm was originally designed in this protocol, but the long-term results suggest that our original concept was probably valid. Further studies, with the possible use also of newer chemotherapeutic agents, may well justify considering this combined therapeutic approach when dealing with this disease in its widespread form.
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PMID:Fifteen years' experience of combined hormone/chemotherapy in metastatic prostate cancer. 153 3

Cyclophosphamide has been considered one of the reference drugs of chemotherapy in randomized trials in hormone-refractory prostate cancer by the National Prostatic Cancer Project (NPCP). Ifosfamide, another oxazaphosphorine agent, and an analog of cyclophosphamide, appears to be more active and less toxic in a broad spectrum of tumors. Fifteen patients with metastatic hormone-refractory prostate cancer were treated with continuous infusion of ifosfamide 2 g/m2 per day for 2 days, together with the uroepithelial protective agent Mesna 2.4 g/m2 per day for 2 days, both to be repeated every 3 weeks. All patients have failed on previous hormonal therapy and 7 patients had received previous chemotherapy. The median age was 66 years. Fourteen patients were evaluable; none of whom achieved an objective response. Four patients were stabilized and 10 had disease progression while on chemotherapy. Major toxicity included 2 reversible encephalopathy, 3 grade I reversible renal toxicity, and 1 hemorrhagic cystitis. We concluded that ifosfamide given in this schedule in this group of patients is not an active agent in prostate cancer.
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PMID:Phase II trial of ifosfamide in the treatment of metastatic hormone-refractory patients with prostatic cancer. 212 44

Endocrine-active and pure antiandrogens have different mechanisms of action and different endocrinological effects in the intact male. With pure antiandrogens as a monotherapy an elevation of plasma testosterone occurs which probably leads to the preservation of potency, the clinical significance of which in the management of prostatic carcinoma is not known. Plasma testosterone is reduced to pretreatment levels after 12 months. Longer observations are not available. In total androgen suppression regimens both types of antiandrogens have been shown in prospective trials to be at least equally effective as standard treatment. The clinical effectiveness of CPA alone in prostatic cancer has been shown to be equal to that of DES 1 mg tid. Sufficiently large prospective studies on flutamide alone in comparison to standard treatment have not been carried out. The use of antiandrogens is recommended during the initial 4 weeks of management of prostatic carcinoma patients with LH-RH agonists to prevent disease flare-up and to achieve higher early response rates in selective patients.
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PMID:Antiandrogenic substances in the management of prostatic cancer. 214 23

A current hypothesis suggests that androgen administration prior to chemotherapy (androgen priming) may potentiate tumor cytotoxicity in prostate cancer. The Dunning R3327G rat prostatic tumor model was used to test this concept experimentally. Control groups without priming included (1) intact untreated, (2) castrate alone and (3) castrate+ chemotherapy (cyclophosphamide, 30 mg/kg/day for 2 days with repeat cycle in 25 days- CTX). Two experimental groups received androgens, one before and one after chemotherapy. Treatment effect was monitored by quantitating tumor volume and animal survival. Control groups receiving castration and chemotherapy had a retardation of tumor growth and a prolongation of survival when compared to untreated animals. Androgen priming before but not after chemotherapy enhanced the degree of tumor suppression. With the androgen-priming protocol, all androgen-primed tumors had regressed, 3/6 tumors had disappeared and 3 were only palpable. At the same time point, tumors in all the other groups were actively growing and had volumes greater than the initial values (P less than 0.01). Median survival was significantly prolonged in primed animals 191 vs 40 days for untreated animals and 150 days for the nonprimed castration + chemotherapy animals (P less than 0.02). These findings have been repeated with several replicate experiments. These observations confirm the hypothesis that androgen priming can potentiate chemotherapy in an experimental system.
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PMID:Androgen-primed chemotherapy-experimental confirmation of efficacy. 228 85

Nearly all men with metastatic prostatic cancer respond to androgen ablation, demonstrating that at least a portion of their cancer cells are androgen responsive. Unfortunately, however, individual prostatic cancers contain clones of androgen-independent, in addition to androgen-responsive, cancer cells. Due to this tumor cell heterogeneity, essentially all patients treated with androgen ablation alone eventually relapse to a state unresponsive to further antiandrogen therapy; cures are rarely produced. To produce cures, additional nonhormonal therapy targeted at the androgen-independent prostatic cancer cells within the patient should be combined with androgen ablation targeted at the androgen-dependent cancer cells. The validity of such combined chemo-hormonal therapy was tested using, as the experimental model, two members of the Dunning system of serially transplantable rat prostatic cancers. Specifically the slow growing, well differentiated H and the fast growing, poorly differentiated G Dunning sublines were used, since these cover the clinical extremes observed for human prostatic cancers. The chemotherapeutic agent used in combination with surgical androgen ablation (i.e., castration) in these studies was Cytoxan. These studies demonstrate that for both the H and G cancer-bearing rats, the mean survival following combined chemo-hormonal therapy was increased above that found for castrate or Cytoxan when either was used as monotherapy. In addition, an inverse relationship between tumor size at the time of initiation of therapy and the ability of the combined chemo-hormonal therapy to cure animal bearing either the H or G sublines was demonstrated. Such combined chemo-hormonal therapy could only cure a proportion (i.e., 30-40%) of H or G tumor-bearing animals if initiated when the tumor was less than or equal to 0.2 cm3 in size. In contrast, if the tumor was 1-2 cm3 in starting size when the chemo-hormonal therapy was initiated, no animal was cured. Neither of the monotherapies (i.e., castrates or Cytoxan alone) could cure any animals regardless of the starting size.
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PMID:Relationship between tumor size and curability of prostatic cancer by combined chemo-hormonal therapy in rats. 280 76

The Dunning R3327 adenocarcinoma represents a model for studying prostate cancer in rats; early studies have indicated its utility for studying relationships between tumor growth, immunologic markers, and chemotherapy. Normal animals and those bearing the metastatic Dunning R3327 MAT-LyLu tumor were treated with 10, 30, and 100 mg/kg doses of cyclophosphamide (CTX) and their spleens assayed for leukocytic subset distributions using monoclonal antibodies. Tumor-bearing animals had significant reductions in helper T cell content as well as reduced helper/suppressor T cell ratios, compared to controls. These effects occurred rapidly following implantation and were not reversed by chemotherapy. When administered to both tumor- and non-tumor-bearing animals, CTX also depleted T cell populations. Despite reductions produced in all subsets, two administrations of CTX (30 mg/kg) were capable of retaining (in non-tumor-bearing animals) or restoring (in tumor-bearing) normal helper/suppressor T cell ratios. Such studies aid in identifying therapeutically effective dosages of cytotoxic drugs that minimize their deleterious effects on the immune system.
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PMID:Effect of cyclophosphamide on leukocytic subset distributions in rats carrying the Dunning R3327-MAT-LyLu prostatic adenocarcinoma. 295 10


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