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At least 811 records · Page 45Linked to original sources
PubMed1998

[Antiandrogen withdrawal syndrome].

The antiandrogen withdrawal syndrome was first reported in patients with prostate cancer who manifested disease progression after total androgen blockage therapy with medical or surgical castration and pure antiandrogen, flutamide; discontinuation of flutamide resulted in a decline in prostate specific antigen and, in some cases, with clinical response. Same phenomena have been reported after the withdrawal of casodex, chlormadinone acetate, megestrol acetate, diethylstilbestrol, and estramustine phosphate. Mutations in the androgen receptor(AR) gene were discovered in clinical specimens of human prostate cancer patients who showed this syndrome and some of these being identical to the mutation found in LNCaP prostate cancer cell line. Another mechanism otherwise the point mutation of AR would be also speculated.

Androgen Antagonists↗
PubMed1998

Management of hormone refractory prostate cancer: current standards and future prospects.

PURPOSE: Recent advances in the biology and treatment of hormone refractory prostate cancer are reviewed. MATERIALS AND METHODS: A MEDLINE literature search of secondary hormonal therapy and chemotherapy for hormone refractory prostate cancer was performed. Recent advances in the biology of hormone refractory prostate cancer, changes in the measurement of response to therapy, and testing of new drugs and combinations of drugs were reviewed. RESULTS: Historically the treatment of hormone refractory prostate cancer has been disappointing. Useful parameters to monitor clinical response have been lacking but perhaps more importantly a scarcity of apparently active drugs has contributed to these results. Recently several developments have improved the outlook for treatment of hormone refractory prostate cancer. Recognition of antiandrogen withdrawal responses has had important ramifications for clinical trial interpretation and patient care. Secondary hormonal therapies, such as alternative antiandrogens and anti-adrenal agents, are well tolerated and can provide significant clinical benefits. Combining prostate specific antigen values with quality of life and measurable disease responses has made clinical trial end points more objective and more clinically relevant for the patient. Furthermore, a better understanding of the biology of hormone refractory prostate cancer, refinements in measuring response to treatment and availability of agents with proved palliative capabilities and/or generating greater than 50% response have all lead to improvements in treatment management. In 2 randomized studies mitoxantrone in combination with steroids has demonstrated significant palliative benefit compared with steroids alone. In phase II studies more than half of patients respond to estramustine combinations with vinblastine, etoposide or paclitaxel. Other novel combinations and new drugs currently are being tested. CONCLUSIONS: Recent advances suggest that available therapies for hormone refractory prostate cancer can have a meaningful impact on the disease. Improving treatment of hormone refractory prostate cancer remains an area of active investigation.

Androgen Antagonists↗
PubMed1999

Novel concept of antisurvival factor (ASF) therapy produces an objective clinical response in four patients with hormone-refractory prostate cancer: case report.

BACKGROUND: Osteoblasts and osteoblast-derived survival growth factors, such as insulin-like growth factor I (IGF I), inhibit chemotherapy apoptosis of prostate cancer cells, thereby producing cytotoxic drug-resistant tumor growth, in vitro. METHODS: We tested a novel therapeutic approach, referred to as antisurvival factor (AFS) therapy, that aimed at reduction of osteoblast-derived IGFs, using dexamethasone (4 mg per os, qD) and growth hormone (GH)-dependent liver-derived IGFs, using a somatostatin-analog (lanreotide, 30 mg, intramuscularly (i.m.), q14D) in combination with triptorelin (3.75 mg, intramuscularly, q28D) to produce a clinical response in 4 patients with progressing hormone-refractory prostate cancer. RESULTS: The patients given ASF therapy exhibited an excellent improvement of clinical performance and a decline of prostate-specific antigen (PSA) within 2 months of ASF therapy. One of them experienced excellent clinical response (normalization of PSA), two experienced good clinical response (decline of PSA of more than 50%), and one experienced stabilization (decline of PSA of less than 50%). CONCLUSIONS: We conclude that this novel concept of combination therapy, using ASF with hormone ablation, is a promising salvage therapy that should be further assessed with a randomized clinical trial.

Aged↗
PubMedDate not supplied

Effect of drug-vinyl copolymer delivery composites on the rat prostate.

A radiation polymerized drug-vinyl copolymer delivery composite (0.8 mm in diameter, 3 mm long) was inserted into the right-lobe ventral prostate (I), into the right testis (II), and subcutaneously (III) into the back of male Wistar rats. The implantation was carried out over a period of 12 weeks maximum. From the relationship between the site of surgical insertion of the implant and the physiologic response (as measured by the decrease in the weight of the prostatic organs, e.g., ventral prostates, dorsolateral prostates, and seminal vesicles), it was found that in an AA560-containing composite (36 micrograms daily), the physiologic response is increased in order of (III) greater than (II) greater than (I). The same tendency was observed in the Estracyt-containing composite system (15 micrograms daily). The difference in the physiologic response owing to the site of surgical insertion of the implant was not observed in an E2-17 beta-containing composite (6 micrograms daily), although this composite showed the strongest physiologic response. No physiologic response in rats with CMA-containing composite (28 micrograms daily) was noted.

Acrylates↗
PubMed1983

The addition of chemotherapy to hormonal therapy for treatment of patients with metastatic carcinoma of the prostate.

Patients with advanced prostate carcinoma that had been stabilized by orchiectomy (ORCH) or hormone therapy for at least 3 months, were randomized to either diethylstilbestrol (DES) alone or DES plus Cytoxan or DES plus Emcyt. A total of 188 patients were randomized between July, 1976 and February, 1982 of which 161 were evaluable for objective response to treatment. Objective response rates, response duration, or survival experiences were not demonstrably different between treatment arms, either for all patients or within good or poor prognosis groups determined by initial pain or acid phosphatase level. Subjective improvements in performance status were small for each treatment. Pain relief was somewhat greater in the chemotherapy-hormone combinations than in the DES/ORCH, but the advantage was not statistically significant. Side effects were primarily nausea and vomiting and leukopenia, mostly in the DES + Cytoxan arm. The duration of stabilization prior to entry did not influence response overall, although there were opposing trends within each of the two chemotherapy arms. The premise for combining antitumor agents with hormones before hormone failure is still felt to be a more logical approach than waiting for the ultimate hormone failure, and a combination of hormones plus two antitumor agents is being evaluated in a subsequent ongoing trial where a more rigid design limits the duration of the preentry period of hormone stabilization.

Aged↗
PubMed1987

Adjuvant treatment of malignant melanoma with DTIC + estracyt or BCG.

Eighty-two patients with invasive malignant melanoma and no distant metastases were prospectively randomized following their surgical treatment to 1) observation; 2) chemotherapy with Dacarbazine (DTIC) 200 mg/M2 I.V. daily X 5 every 4 weeks and Estracyt 15 mg/kg orally daily for 1 year; and 3) immunotherapy with TICE BCG 1 ml to an area of scarification near the primary site, every 4 weeks for 1 year. At a median follow-up of 73.4 months 31 patients (38%) have relapsed. There was no significant difference in survival according to the treatment, but a weak effect on the course of the disease by either of the treatment protocols cannot be ruled out due to the small sample of patients. Survival and disease-free interval varied significantly according to the histologic status of the regional nodes. The estimated 5-year disease-free rate of patients with negative nodes was 85% and for those with positive nodes it was 35% (P less than 0.0001).

Administration, Oral↗
PubMed1980

Adjuvant chemotherapy to definitive treatment of prostate cancer.

Even though surgery and/or radiation has been the treatment of choice of early carcinoma of the prostate, there is conclusive evidence that tumor may recur in a certain number of patients at the primary site and/or at a distant location. The only way to achieve a complete cure in these patients with localized cancer appears to be by addition of relatively safe, effective chemotherapeutic agents. Estracyt and/or Cytoxan appear to be such agents. These two drugs showed definite activity in the treatment of patients with advanced prostatic carcinoma. Chemotherapeutic agents appear effective as adjuvant in the treatment of other solid tumors. It is worthwhile that this modality of treatment be tried in patients with early, curable prostatic carcinoma.

Antineoplastic Agents↗
PubMed1984

International overview on the treatment of prostate cancer--Scandinavian experience.

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.

Antineoplastic Agents↗
PubMed1991

Investigation on serum neurone-specific enolase in prostate cancer diagnosis and monitoring: comparative study of a multiple tumor marker assay.

A quadruple tumor marker serotest assay (neurone-specific enolase, NSE, prostate-specific antigen, PSA, prostatic acid phosphatase, PAP, and carcino-embryonic antigen, CEA) was performed on sera from both 63 patients with untreated prostate cancer and 135 patients treated with orchiectomy, flutamide, diethylstilbestrol (DES), cyproterone acetate (CPA), and Estracyt. In untreated patients with local tumor elevated blood NSE concentrations were found more frequently (10/35, 28.6%) than in untreated subjects with disseminated disease (3/28, 10.7%). Elevated NSE values were measured more frequently in nonresponders to therapy 10/46 (21.7%), than in responders during prostate cancer partial remission (2/89, 2.2%). In none of NSE-positive neoplasms a small cell prostate cancer has been histologically detected. Many of NSE-positive tumors are also closely associated with elevated blood CEA values. The applied anticancer drugs were inefficient in the normalization of neither one from the pair of elevated NSE and CEA concentrations (regardless of the numerical values of the other two markers, PSA and PAP), but their values were found to decline occasionally only after surgical treatment. In patients with raised PSA, PAP, and CEA levels but with a normal NSE value, the application of the same treatment strategies was in the most of subjects sufficient to provoke either temporary or even lasting tumor response to therapy. Hence, it appears that the assessment of the NSE serotest, despite its minimal value in the overall tumor staging and monitoring, might furnish the decision-making step related to the treatment of aggressive prostate cancer with an additional and powerful tool.

APUD Cells↗
PubMed1992

NK cell activity in treated prostate cancer patients as a probe for circulating tumor cells: hormone regulatory effects in vivo.

Natural killer (NK) cell activity was studied together with tumor marker serotests (PSA, PAP) and blood testosterone, estradiol, cortisol, and prolactin concentrations in treated prostate cancer patients. NK cell activity data were correlated with tumor stage (stage D0 + D1 versus stage D2) and showed statistically insignificant differences. Both tumor progression and stabilization of metastatic disease, triggered by the application of more appropriate therapy in progressive subjects, yielded low NK activity data. By contrast, normal NK activity was found during both partial remission of stage D2 tumor and stabilization of the same disease, after an initial period of tumor remission. Differences between NK activity data from the aforementioned two groups are statistically significant (P less than 0.01). In subjects examined, the application of NK activity assay to those with advanced disease reflected changes in the outcome of the treatment more closely than it did routine tumor marker assessment. The activity of NK cells seems unaffected by changes in basal blood estradiol, cortisol, testosterone, and prolactin concentrations that occur during therapy with pharmacological agents (estradiol, cyproterone acetate, diethylstilbestrol, and flutamide) and during surgical castration. The reported NK activity recordings in treated prostate cancer patients might be indicative of the presence of tumor cells in the circulation. If this holds true, the measurement of NK activity would appear to furnish urological oncology with a new tool for early, rapid recognition of progressive metastatic tumors.

Acid Phosphatase↗
PubMed1996

A new scalable purification procedure for prostatic secretory protein (PSP94) from human seminal plasma.

A simple three-step procedure for the purification of native prostate secretory protein (PSP94) from human seminal plasma is described. The steps are ammonium sulfate fractionation followed by a Macro-Prep S support (cation) flowthrough process and the final Macro-Prep high Q support (anion exchange) chromatography using two step-gradient elution. The benefits of this procedure lie in its simplicity, speed, and relatively inexpensive materials, thus providing advantages over the previously reported schemes. The purity of the product as judged by single band on SDS-polyacrylaminde gel electrophoresis was equivalent to that attained by analytical HPLC anion exchange procedure. Yields were in the range of 18-25 mg highly pure PSP94 per 50 ml of seminal plasma. The desalted, lyophilized, purified PSP94 sample was characterized by SDS-PAGE, Western blot, and N-terminal sequencing. All parameters tested confirm its identity. Preliminary data show that this procedure is suitable for a large-scale production. The direct quantitation of PSP94 by SDS-PAGE and densitometric image analysis at various purification steps for evaluating the recovery of PSP94 is described. The results obtained show that this is an efficient strategy for preparation of highly purified native PSP94.

Blotting, Western↗
PubMed1992

Computed tomographic evaluation of bone metastases in prostatic cancer patients.

This report provides new morphological insights, based on diagnostic methods, into metastases to the bone in prostate cancer patients. Lumbar CT examination is available to evaluate whether metastases are truly present or not, especially in aged patients with positive bone scans. The evaluation of response is clearer on CT. Furthermore, CT is useful not only in estimating the presence of metastases, CT also provides definite details on the extent of the metastatic condition.

Aged↗
PubMed1992

The usefulness of serum acid phosphatase in monitoring patients with advanced prostate carcinoma.

The usefulness of serum acid phosphatase (SAP) in monitoring patients with advanced prostate carcinoma has been questioned. We reviewed a series of 59 patients with stage D2 prostate carcinoma. All patients had extended follow-up through at least one clinical relapse, or death. Responses to a variety of therapies were characterized as absent, subjective, or objective. All patients with an elevated pre-treatment SAP that fell to normal following therapy had prolonged survivals and improved prognoses. Conversely, all patients with an elevated SAP which did not normalize following therapy had poorer survivals. Among 36 objective responses to therapy, the SAP was elevated prior to or simultaneous with disease progression in 33 (93% sensitivity). In each ease where the pretreatment SAP normalized following therapy, any subsequent elevation in SAP above normal was always associated with clinical evidence of disease progression (100% specificity). Changes in SAP following therapy correlate well with both disease regression and disease progression in patients with advanced prostatic carcinoma.

Alkaline Phosphatase↗
PubMed1996

Therapy for hormone-resistant prostate cancer: no longer a myth.

In conclusion, there have been impressive efforts to identify new cellular targets for the treatment of hormone-refractory disease. It appears that in some cases, survival may be extended; however, further prospective trials are necessary to confirm these observations.

Antineoplastic Agents, Hormonal↗