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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on the pertinent literature, this paper discusses the results of cytostatic therapy for advanced prostatic cancer published so far with special consideration given to the extensive experience of the National Prostatic Cancer Project (NPCP) in the United States. Endoxan and 5-Fluoro-uracil, each as a monotherapy, haven proven still to be the optimal cytostatic therapies in secondary treatment following hormone resistance. Moreover, our own results reached with 33 patients on chemotherapy with Endoxan or 5-Fluoro-uracil, resp., are reported, in particular those in 24 of the 33 patients receiving these drugs as a third therapy after previous hormone resistance and secondary Estracyt resistance. Especially with regard to pain relief, we obtained good results in 50% of cases. The average survival period of the patients on third therapy was 6.7 months. Side effects prevailed in the gastrointestinal tract and the hemopoetic system. The results with Endoxan and 5-Fluoro-uracil as primary therapies have thus far been unsatisfactory with regard to therapy response and drug tolerance.
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PMID:[Cytostatic therapy of prostatic carcinoma. Current status and personal results]. 635 55

The efficacy of chemotherapy for prostatic cancer is difficult to evaluate owing to the low incidence of measurable indicator lesions and the resulting need for indirect response criteria. Although complete regressions remain exceptional, a number of agents, eg, doxorubicin and cisplatin have been shown to be effective in the treatment of this disease. So far, combinations of effective agents with or without concomitant hormone therapy have not proven to be more effective than single agents. Androgen priming has considerable theoretical appeal and deserves further consideration. A higher effectiveness of chemotherapeutic agents might be obtained by linkage to various carriers. Estramustine phosphate is an example of such a complex that has a cytotoxic effect in test systems in which estrogen has no effect and in patients with hormone-refractory prostatic cancer. The use of hormonal and other carriers that could increase the specificity of chemotherapeutic agents deserves extensive exploration.
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PMID:Chemotherapy principles in the treatment of prostatic cancer. 636 76

Estramustine phosphate is approved by the Food and Drug Administration for oral use in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a conjugate of 17 beta-estradiol and the carbamate of nitrogen mustard. Although its therapeutic efficacy has been demonstrated, it is not clear to what extent each constituent contributes to estramustine's effectiveness. Estramustine phosphate therapy achieves objective response rates of 60-90 percent in advanced stage D prostatic cancer patients with no prior hormonal therapy. These results are consistent with those obtained with conventional hormonal therapy in similar patient populations. Therapeutic efficacy does not appear to increase when estramustine is used concurrently with other cytotoxic chemotherapeutic agents. An objective response rate of 20-30 percent can be anticipated in patients refractory to conventional hormonal therapy. It is in this group, the estrogen-resistant patients, that estramustine shows the most promise. Adverse effects of estramustine are similar to those of diethylstilbestrol. Gastrointestinal and cardiovascular side effects appear to be the most important and may be severe enough to require discontinuation of therapy.
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PMID:Estramustine phosphate sodium. 637 12

In May 1978, the National Prostatic Cancer Project Treatment Subgroup activated its first clinical trial evaluating adjuvant chemotherapy (Protocol 900). This protocol is a comparison of long-term adjuvant chemotherapy with cyclophosphamide, estramustine phosphate, or no additional treatment in patients with definitive surgical therapy for adenocarcinoma of the prostate. To date, 128 patients have been entered with an entry rate of approximately 2.2 patients per month. One hundred five patients form the basis of this report, with 96 patients still on active therapy. Estramustine phosphate has been administered at a dose of 600 mg/m2 orally daily in three divided doses. The cyclophosphamide is administered 1 g/m2 intravenously every 3 weeks. Results are still preliminary; only two evaluable patients have died. Approximately two-thirds of patients entered have had negative lymph nodes. Recurrent disease has been documented in 15 patients, including eight receiving cyclophosphamide, three receiving estramustine phosphate, and four on the no-treatment arm. The recurrence rate has been disproportionately high (50%) in patients receiving cryosurgery rather than radical prostatectomy (12%). Maximum survival has reached 241 weeks. Side effects have consisted of leukopenia in patients receiving cyclophosphamide (56%), and nausea and vomiting with cyclophosphamide (85%), and estramustine phosphate (36%). This study continues with patient entries now over one-half of the number anticipated in the original study design.
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PMID:Cooperative clinical trials of the National Prostatic Cancer Project: Protocol 900. 637 83

Estracyt is a new drug for treatment of prostatic cancer, which is a molecule combining estradiol and nornitrogen mustard by a carbamate link. Estracyt is completely dephosphorylated prior to reaching the peripheral circulation after oral administration of the drug to men. Estramustine, i. e. dephosphorylated Estracyt, appears to be metabolized in liver as follows: Estramustine leads to estromustine leads to nitrogen mustard + estrone. There is a large amount of estramustine binding protein (EMBP) in the cytosol 3.5 S fraction of human prostatic cancer tissue, which is involved with the selective uptake and long term retention of both estramustine and estromustine in prostate. The anticancer action of Estracyt appears to be the sum of the direct prostatic action of estramustine and estromustine and the indirect prostatic action of free estradiol-17 beta and estrone via the inhibition of hypothalamo-pituitary axis. Estracyt Research Group in Japan concluded that Estracyt was effective in 38% of reactivated prostatic cancer patients (15% (I-C, I-B), 23% (I-A, O-B, O-C]. Side effects of this drug at the time of 3 months treatment is as follows: gastrointestinal disturbance in 36%, edema in 15%, and hepatic disorder in 7%.
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PMID:[Pharmacology and metabolism of a new therapeutic drug for prostatic cancer "Estracyt"]. 642 61

Estracyt (estramustine phosphate) is a nitrogen mustard derivative of estradiol-17 beta which is rapidly dephosphorylated to yield estramustine. Estramustine is metabolized to estromustine mainly in the liver. Both estramustine and estromustine are retained in rat prostate with a high degree of specificity. This retention is due to the binding of estramustine and/or estromustine to a protein called EMBP (estramustine binding protein). When estimated by HPLC, the molecular weights of these estramustine binding components in rat prostate are 45,000-50,000 and 25,000-30,000, respectively. HPLC and glycerol density gradient analysis clearly demonstrated the occurrence of EMBP in a cytosol preparation from human prostatic cancer tissue. When estimated by HPLC, the molecular weights of estramustine binding components are 45,000 and 25,000 daltons, respectively. In addition, results of effectiveness of Estracyt studied under a cooperative research group in Japan, are reported in this paper. Effectiveness was evaluated at 3 months of the treatment on 121 patients with untreated prostatic cancer (Study I) and 95 patients with reactivated cancer (Study II), at 12 months of the treatment on 68 patients in Study I and 85 patients in Study II, and at 24 months on 37 patients in Study I and 23 patients in Study II. At 3 months of the treatment, Estracyt was effective in 89% of untreated prostatic cancers, and 38% of reactivated prostatic cancers. At 24 months of the treatment, this drug was effective in 65% of untreated prostatic cancers and 30% of reactivated ones. Estracyt is especially recommended as a first-choice drug for both the untreated patients with poorly differentiated adenocarcinoma and reactivated cancer.
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PMID:[Estracyt (estradiol-nitrogen mustard complex)--estramustine binding protein and its specificity]. 648 30

Estramustine phosphate, a combination steroid and alkylating agent, has been used for treatment of cancer of the prostate since 1969. We treated 32 patients with Stages C and D prostate cancer with this compound. Using the National Prostatic Cancer Project criteria of response, no patient achieved complete or partial objective response. Sixty-two per cent of the patients without prior hormonal manipulation and 12 per cent of those who were progressing following hormonal therapy met the criteria for a stable response. Both Stage C patients, 50 per cent of D1 and 28 per cent of D2 patients achieved disease stabilization for a mean duration of 14.8 months. There was no correlation between tumor grade and response to treatment. Fifty per cent of the patients whose elevated acid phosphatase declined remain stable, whereas 80 per cent in whom the acid phosphatase did not decline have progressed. Estramustine is effective in patients without prior hormonal manipulation. In those refractory to hormones, the prognosis is poor yet data exist to support the superiority of estramustine phosphate over conventional therapy.
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PMID:Estramustine phosphate--hormone, chemotherapeutic agent, or both? 653 98

Thirty-five patients with advanced cancers were treated with estramustine phosphate tablets (Estracyt). Doses ranged between 420 mg and 700 mg daily. One partial response was documented in a hormone resistant prostatic cancer patient. Four minor responses (less than 50% responses, or less than one month more than 50% response) were obtained; one in a hormone resistant prostatic cancer, two in metastatic colorectal cancers; and another in a malignant melanoma. Toxicity phenomena included nausea (9/35 - 25%), water retention (4/35 - 11.5%) and mild elevation of alkaline phosphatase (2/35 - 6%). Other toxicity effects were vaginal bleeding in two women, acne in one woman and mild pruritus in another patient. Myelosuppression and immune suppression were not significantly detected.
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PMID:Oral estramustine phosphate (Estracyt): a broad phase II study. 659 4

The Scandinavian countries, especially Sweden and Norway, have a high incidence of prostate cancer. The tumor classification has been mainly uniform in recent years, according to the TNM system. Transrectal fine-needle biopsy and cytologic malignancy grading were introduced in Sweden and were gradually accepted in other countries. The treatment of prostate cancer has been mainly conservative as it is in most parts of Europe. For a long period endocrine therapy was given in the vast majority of cases. In recent years radiotherapy has also been used in cancer of low differentiation with no evidence of dissemination. In poorly differentiated and disseminated disease, Estracyt is the standard therapy. Estracyt is also given in disseminated carcinoma nonresponsive to ordinary hormone therapy. In this category of patients other chemotherapy is the second therapeutic alternative. Various techniques of endocrine therapy, chemotherapy, and radical surgery are subject to controlled trials.
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PMID:International overview on the treatment of prostate cancer--Scandinavian experience. 673 73

This article is a review of the results of chemotherapy for advanced hormonally-unresponsive prostatic carcinoma. Although the only hope for treatment of these patients is chemotherapy, until recently relatively little emphasis has been placed on chemotherapy of prostatic cancer. Since results of the randomized trial of the National Prostatic Cancer Project in the United States revealed a demonstrable advantage of advanced hormonally-refractory disease, a number of studies has been done and reported. As single chemotherapeutic agent, cyclophosphamide (CPM), 5-fluorouracil (5-FU), Adriamycin (ADM), and Cisplatinum (CDDP) have activity in these patients. Estracyt has been reported very effective, but has been somewhat disappointing in American trials. Several combination chemotherapies have been reported effective, such as CPM + ADM, CPM + ADM + Methotrexate (MTX), and CPM + MTX + 5-FU + Vincristine, Prednisone. Presently, however, there is no evidence that combination chemotherapy in prostatic cancer is better than single-agent chemotherapy. The need for continued effort to search powerful new agent, and to establish more effective combination chemotherapy for prostatic cancer should be emphasized. Furthermore, the importance of randomized and stratified clinical trials, early and late in the course of the disease, is stressed.
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PMID:[Chemotherapy of hormone-unresponsive prostatic cancer and its metastatic foci]. 676 5


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