fosfestrol and Prostatic-Neoplasms

In our institution, rotational 3D-conformal radiation therapy (also called conformation therapy) has been applied since the late 1970s to conform the target volume of high-dose radiation to the cancerous tissue while minimizing radiation to the surrounding normal tissues. This technique has been used most commonly to treat prostate cancers in combination with hormonal therapy. The results of Stage B2/C prostate cancer treated with this method were analyzed.. Between 1987 and 1997, 33 cases of prostate cancer were definitively treated with this method: 9 Stage B2 tumors and 24 Stage C tumors. Of these 33 tumors, 3 were well differentiated, 18 were moderately differentiated, and 12 were poorly differentiated. The average patient age was 75.6 years. The median pretreatment PSA value was 23.8 ng/ml. The total radiation dose ranged from 60 Gy to 70 Gy (average: 63.5 Gy) with conventional fractionation. Hormone therapy was administered permanently; the primary hormonal agent was diethylstilbestrol phosphate.. The overall survival rate after 5 years was 58.2% and that after 10 years was 29.6%. The biochemical relapse-free rate after 5 years was 87.0% and that after 10 years was still 87.0%. There were 4 cases of biochemical failure, but no cases of death from prostate cancer. Stage, differentiation, and pretreatment PSA value were not prognostic factors. One of the 2 cases with delayed complications was a case of RTOG Grade 3 gastrointestinal complication.. Rotational 3D-conformal radiation therapy combined with hormone therapy might be promising for the treatment of prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Chlormadinone Acetate; Diethylstilbestrol; Disease-Free Survival; Flutamide; Follow-Up Studies; Gastrointestinal Diseases; Goserelin; Humans; Imaging, Three-Dimensional; Japan; Life Tables; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostatic Neoplasms; Radiation Injuries; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Retrospective Studies; Rotation; Survival Analysis; Treatment Outcome; Urination Disorders

Topics: Administration, Oral; Animals; Antineoplastic Agents, Hormonal; Apoptosis; Depression, Chemical; Diethylstilbestrol; Humans; Infusions, Intravenous; Male; Pituitary Gland; Prostatic Neoplasms; Testosterone; Treatment Outcome

The syndrome of inappropriate secretion of antidiuretic hormone (ADH) was recognized in a 68-year-old man with a poorly differentiated metastatic adenocarcinoma of the prostate. Elevated levels of ADH were found in the tissues of the primary tumor and lymph node metastasis. The patient's clinical course is detailed and the pathophysiology of this syndrome is discussed. To our knowledge, this case is the ninth reported case of syndrome of inappropriate secretion of ADH with adenocarcinoma of the prostate. Antidiuretic hormone activity was proven in only three cases including this case.

Topics: Adenocarcinoma; Aged; Diagnosis, Differential; Diethylstilbestrol; Humans; Inappropriate ADH Syndrome; Lymphatic Metastasis; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Sodium; Vasopressins

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Diethylstilbestrol; Drug Administration Schedule; Humans; Male; Middle Aged; Prostatic Neoplasms

Topics: Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms

We report one case of Paneth cell-like change of prostate cancer. An 81-year-old male reported to our hospital with the chief complaint of urinary retention. The serum concentration of prostate specific antigen, 168 ng/ml, was high, and digital examination was performed. Because we suspected prostate cancer, needle biopsy of the prostate was performed. Histological examination revealed moderately-poorly differentiated adenocarcinoma. Computed tomography revealed no invasion to the prostatic wall and no metastasis to the lymph node. 99mTc-HMDP revealed no bone metastasis. We chose intravenous hormonotherapy (fosfestrol 500 mg/day, 20 days), but urinary retention did not improve. Therefore, we performed transurethral prostatectomy to improve the symptoms. Histological examination of the removed specimen revealed moderately differentiated adenocarcinoma with Paneth cell-like change. Immunochemical and histochemical stains were positive for Grimelius, serotonin and prostatic acid phosphatase and negative for periodic acid-Schiff reaction, lysozyme, neuron specific enolase, prostate specific antigen, alpha-1-antitrypsin and IgA.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

The initial treatment of advanced-stage prostate cancer is total androgen deprivation. Autonomous proliferation of primarily or secondarily hormonal unresponsive cells may explain the development of hormone-refractory status. The median survival of patients with hormone-resistant disease is short; there is no standard regimen of chemotherapy.. Fosfestrol or diethylstilbestrol diphosphate and its metabolites have cytotoxic activity in hormone-refractory prostatic cell lines. Pharmacokinetic studies have shown that fosfestrol metabolites have a short half-life that supports the use of long-term infusion in the clinic.. A review of the literature shows that high-dose fosfestrol induces no objective response, a greater than 50% tumor marker decrease in 50% of patients, a subjective improvement in 75% of patients, and cardiovascular complications in 5% of patients. The median survival time of patients is 5 months after the onset of treatment.. An exact evaluation of the role of high-dose estrogens requires additional investigation.

Topics: Aged; Antineoplastic Agents; Diethylstilbestrol; Drug Resistance; Humans; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Tumor Cells, Cultured

Three cases of prostatic carcinoma with palpable metastatic lymph nodes are presented. In case 1, the intrapelvic lymph node metastases were recognized as an abdominal mass. In case 2 and 3, non-regional superficial lymph node metastases were palpable. Orchiectomy and anti-androgen therapy were effective in all cases.

Topics: Adenocarcinoma; Aged; Combined Modality Therapy; Diethylstilbestrol; Estramustine; Humans; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

A prostate biopsy was carried out in a 53-year-old male outpatient with disseminated prostatic carcinoma. Two days later, he was admitted with severe acute anaemia (haemoglobin: 48 g.l-1) and macroscopic haematuria. Biological investigations revealed a disseminated intravascular coagulation (DIC). Symptomatic treatment was undertaken (transfusion of packed red blood cells, platelets, fresh frozen plasma and fibrinogen). However, the patient's condition worsened, and he was admitted to the intensive care unit 48 h later. Despite appropriate symptomatic treatment, the patient's condition continued to worsen. The prostatic origin of this condition was therefore suspected, and anti-androgenic treatment was started on day 9 (1,200 mg.day-1 ketoconazole and 2,000 mg.day-1 sodium fosfestrol). Within 48 h, the patient had began to recover in quite a spectacular manner. Ketoconazole starts blocking steroid synthesis within 4 h of giving it. This treatment can be used until oestrogen therapy starts having an effect (about one week). The low levels of testosterone in this case, before starting treatment, suggest that ketoconazole acted on the DIC by a possible cytotoxic effect on the carcinomatous cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Biopsy, Needle; Blood Coagulation Tests; Diethylstilbestrol; Disseminated Intravascular Coagulation; Humans; Ketoconazole; Male; Middle Aged; Prostatic Neoplasms

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.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Survival Rate

Topics: Buserelin; Castration; Chorionic Gonadotropin; Cosyntropin; Dexamethasone; Diethylstilbestrol; Estrogens; Goserelin; Hormones; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

A novel hormone therapy was instituted against prostate cancer with bone metastases and its therapeutic efficacy was investigated.. A total of 35 patients who had been pathologically diagnosed with carcinoma of the prostate between December [corrected] 1994 and December 2003 were entered into the present study. Patients aged over 80 years were excluded from the study. As for the treatment methodology, diethylstilbestrol diphosphate (DES-P) at 500 mg/day was intravenously injected for 20-40 days, followed by monotherapy with an analog of luteinizing hormone-releasing hormone (LHRH). In all subjects, surgical castration was not conducted. The survival rate was analysed according to the method of Kaplan-Meier.. One of the 35 patients was excluded from the study as this patient did not meet the inclusion criteria. There were four patients who dropped out of the study. On histology, 17 patients had moderately differentiated adenocarcinomas and 17 patients had poorly differentiated adenocarcinomas. As for the extent of disease (EOD), the patients were classified as with a score of 1 in 10 patients, 2 in 13 patients, 3 in 7 patients and 4 in 4 patients. The 5-year progression-free survival rate and overall survival rate were 24.3% and 60.6%, respectively.. Our new hormone therapy in the management of prostate cancer metastatic to the bone has demonstrated markedly superior therapeutic results compared to those so far obtained.

Topics: Adult; Aged; Bone Neoplasms; Diethylstilbestrol; Disease Progression; Dose-Response Relationship, Drug; Drug Therapy, Combination; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Survival Rate

We investigated the influence of flutamide on plasma adrenal androgens in advanced prostate cancer patients treated with dietylstilbestrol diphosphate (DES-DP) followed by luteinizing hormone-releasing hormone agonist (LH-RH agonist). Nine patients were enrolled in this study and they were divided into the following two treatment groups; group A: LHRH agonist mono-therapy (n = 4) and group B: LHRH agonist with flutamide (n = 5). For prevention of flare up, all patients were treated with DES-DP.. Two-week DES-DP administration led to reduction of plasma adrenal androgen levels. These levels were kept lower for 16 weeks in group B in contrast with group A in which the levels returned to the pretreatment levels. Basal ACTH levels in group B were significantly lower than those in group A.. From our observations, we found that flutamide reduced adrenal androgen levels in prostate cancer patients treated with LH-RH agonist. ACTH suppression might be related to this phenomenon.

Topics: Adrenocorticotropic Hormone; Aged; Androgens; Depression, Chemical; Diethylstilbestrol; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

This prospective and randomized clinical study was initiated to compare the efficacy and safety of combined androgen blockade with combination with UFT in patients with untreated prostate cancer.. A total of 142 patients were entered in this study between April 1990 and December 1992. All patients received bilateral orchiectomy and 200 mg/day of diethylstilbestrol diphosphate. Of these patients, 70 patients were administered an additional 400 mg/day of UFT after randomization. Either treatment was continued for at least 1 year or until objective progression occurred if the initial response was equal to or better than no change. The endpoints of this study were progression-free survival, cancer-specific survival and change of QOL scores.. A total of 136 patients were evaluable and 131 patients (96.3%) could be followed up with a median follow-up period of 1469 days. Both groups showed similar initial treatment response at 12 weeks, adverse effect and change of quality of life score during the first year after initiation of the treatment. There was a significantly longer progression-free survival and better but not significant cancer-specific survival in the endocrine chemotherapy group. The patients with earlier stage and initial serum prostate-specific antigen values <40 ng/ml showed a good indication for this endocrine chemotherapy.. This endocrine chemotherapy was confirmed to be tolerable and significantly effective in the delay of disease progression, which leads to longer survival in patients with prostate cancer.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diethylstilbestrol; Disease-Free Survival; Humans; Male; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Quality of Life; Tegafur; Uracil

To determine whether administration of estrogen or gestagen prior to luteinizing hormone-releasing hormone (LH-RH) agonist prevents disease flare in prostate cancer patients, we pretreated the patients with either diethylstilbestrol diphosphate (DES-P) 300 mg daily (N = 17) or chlormadinone acetate (CMA) 100 mg daily (N = 16) or none (N = 16) for two weeks before the initial injection of leuprolide acetate (L). Blood samples for prostatic specific antigen (PSA), testosterone (T), and luteinizing hormone were collected before CMA and DES-P administration, before and at 2, 7, 14, 28, 56, and 84 days after the first administration of leuprolide. The treatment with DES-P and CMA prior to LH-RH agonist induced an early decline of PSA. The mean PSA level showed no significant secondary rise in those patients with pretreatment after L administration. In the patients pretreated with DES-P or CMA, the mean serum T level never exceeded the pretreatment baseline after L administration. On the other hand, in the patients without DES-P or CMA, both serum T and PSA levels increased after the first administration of L. These results clearly demonstrate that pretreatment with DES-P 300 mg daily or CMA 100 mg daily for 2 weeks is quite effective to prevent disease flare after the first administration of L in patients with prostatic cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Autacoids; Chlormadinone Acetate; Diethylstilbestrol; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Neoplasm Recurrence, Local; Premedication; Progesterone Congeners; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

High dose intravenous stilboestrol has a direct cytotoxic effect on prostatic carcinoma cells. The purpose of this study was to assess subjective and objective responses in a select group of patients with metastatic, hormone-refractory carcinoma of the prostate with severe generalized bone pain in association with symptoms of advanced local disease.. Seventeen patients with metastatic carcinoma of the prostate, who had relapsed following a good initial response to androgen ablation, were treated as inpatients with once daily intravenous injection of 1104 mg diethylstilboestrol diphosphate (Honvan, Asta Medica, Cambridge, UK) for 7 days. The hormone-refractory status was confirmed by castrate serum testosterone levels. All the patients had failed to respond to second-line hormone manipulation and had progressive disease. All the patients had generalized bone pain, 11 also had symptoms of bladder outlet obstruction, 3 had recurrent haematuria and 3 had both. The mean age was 74 years (range 59-83), mean time to chemical relapse (rising PSA) was 29 months (range 1-70), and mean time to clinical relapse was 37 months (range 6-98). The WHO pain score, performance status score, and a patient-specific quality of life (daily living activity) were used as the subjective measures and the serum PSA as an objective marker. All the parameters were recorded before, during and up to three months after treatment.. Two patients had a transient relief of bone pain with the pain score reducing by two points. Overall, the pain and performance scores and the local symptoms did not improve. The PSA level continued to rise in all patients. Despite parenteral pre-medication with pethidine and cyclizine, all the patients suffered nausea and pain following the injection. One patient died on the fifth day of treatment from a myocardial infarction and 4 developed deep vein thrombosis. All the patients required further symptom control measures.. High dose intravenous stilboestrol causes considerable morbidity without any objective or subjective response in the treatment of patients with symptomatic, hormone-refractory metastatic carcinoma of the prostate.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma; Diethylstilbestrol; Humans; Injections, Intravenous; Male; Middle Aged; Nausea; Pain; Prostatic Neoplasms; Treatment Outcome

A prospective randomized joint study was conducted to evaluate the usefulness of UFT 1) as a postoperative adjuvant therapy in patients with invasive bladder cancer who had undergone curative combination therapy with operation and/or chemotherapy and/or radiation therapy, 2) as an endocrine chemotherapy in patients with newly diagnosed stage C/D prostate cancer, for a period of 3 years from January, 1992. For bladder cancer, of 36 patients with invasive bladder cancer, clinically cured by combination therapy, 20 patients were treated with UFT as an adjuvant chemotherapy over 12 months, and they were compared to 16 patients with no adjuvant therapy. After excluding 10 inappropriate patients, 12 patients in the UFT treatment group and 14 patients with no adjuvant treatment group were observed. For prostate cancer, of 29 patients with clinically stage C/D prostate cancer, 13 were treated with endocrine therapy in combination with UFT, and 16 patients were treated with endocrine therapy alone. After excluding 7 inappropriate patients, 10 patients with endocrine chemotherapy and 12 patients with hormonal therapy were observed. The non-recurrence rate, survival rate and side effects of UFT were evaluated. In the study of bladder cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. In the study of prostate cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. These findings suggest UFT is less useful as an adjuvant therapy for the invasive bladder cancer and as an endocrine chemotherapy for newly diagnosed advanced prostate cancer.

Topics: Administration, Oral; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Diethylstilbestrol; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Prostatic Neoplasms; Tegafur; Uracil; Urinary Bladder Neoplasms

Serum levels of LH, FSH and testosterone (T) were measured by radioimmunoassays in 36 patients with advanced prostate cancer before and during androgen ablation therapies. Both leuprolide acetate (LH-RH agonist: LHRH-A) and diethylstilbestrol diphosphate (DES-DP) administration decreased serum LH significantly to an undetectable level (LHRH-A: P < 0.01, DES-DP: P < 0.05). LHRH-A and DES-DP diminished serum FSH to 20% of the pre-treatment level (P < 0.005) and to an undetectable level (P < 0.001), respectively. LHRH-A and DES-DP decreased serum T to the castration level and an undetectable level, respectively (P < 0.001). Serum levels of the same 3 hormones before and after DES-DP administration were measured in 8 patients who received DES-DP after LHRH-A treatment or castration because of relapse of the disease. DES-DP lowered serum FSH further than LHRH-A to an undetectable level (P < 0.005) and diminished T further than previous treatments to an undetectable level (P < 0.05 vs. LHRH-A, P < 0.01 vs. castration). These results suggest that 1) DES-DP is able to reduce T production from extra-testicular site(s), and achieve the minimal serum T level, and 2) this DES-DP action appears to be one of the mechanisms of the effectiveness of the estrogen on refractory prostate cancer after castration or LHRH-A. In addition, basal (independent of LH-RH) FSH secretion in elderly men is about 20% of total FSH secretion and DES-DP inhibits the basal FSH secretion at the level of the pituitary.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Diethylstilbestrol; Follicle Stimulating Hormone; Humans; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms; Receptors, LHRH; Retrospective Studies; Testosterone

To determine whether long-term oral administration of UFT, a combination of 5-fluorouracil and uracil, in addition to conventional estrogen therapy improved the response and survival of the patients with advanced stage D2 prostate adenocarcinoma, a randomized prospective study was performed with either estrogen alone (Honvan 200 mg/day or presexol 1 mg/day: group A) or estrogen plus UFT (400 mg/day:group B). This study comprises 34 newly diagnosed patients with poorly differentiated prostatic adenocarcinoma (18 patients in group A and 16 in group B). Survival from all causes of death or cancer-specific death were compared using Kaplan-Meier actual methods among the patients separated by histological composition of tumors analyzed WHO histologic patterns, score of extent of disease (EOD), and with or without normalization of serum PSA or PAP levels after treatment. Although combination therapy with UFT against overall survival was effective without statistical significance, better survival in this group than the patients treatment with estrogen alone assessed among the patients whose tumor contained more than 70% of medullary and/or column-cord histological components. The survivals among the patients with EOD score 3 and whose serum PSA or PAP levels did not lead to decrease within normal levels after treatment were also better in group B than in group A. These findings suggest the validity of the combination therapy with UFT in addition to estrogen against highly advanced prostatic cancer patients whose tumor composed of abundant non-hormone-refractor histological components.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Humans; Japan; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostatic Neoplasms; Survival Rate; Tegafur; Uracil

Prognosis of hormone-refractory prostatic cancer is dismal. We evaluated the efficacy of cytotoxic chemotherapy in combination with hormone therapy in patients with newly diagnosed metastatic prostatic cancer.. From February 1984 to March 1992, 39 newly diagnosed patients with stage D2 prostatic cancer were randomized to orchiectomy plus diethylistilbestrol diphosphate or orchiectomy plus diethylstilbestrol diphosphate plus combination chemotherapy with cisplatin and methotrexate.. There was not significant difference in survival or progression-free survival between the two groups.. Chemotherapy has not been proved to prolong survival or progression-free survival in patients who received hormone therapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Diethylstilbestrol; Disease-Free Survival; Humans; Male; Methotrexate; Orchiectomy; Prostatic Neoplasms

The objective of this study is to investigate the pathological changes which occurred in prostatic cancer shortly after the commencement of endocrine therapy.. Fourty-three patients underwent radical prostatectomy immediately after the short term endocrine therapy (treatment period was within one month) and the histological pictures of operative specimens were compared to those obtained from the pretreatment biopsy specimens.. Degenerative changes of cancer cells, such as nuclear and cytoplasmic vacuole, collapse of the cytoplasm and the appearance of naked hyperchromatic nucleus were noticed after the short term endocrine therapy. Especially in the cases which were histologically evaluated to be poorly differentiated in the biopsy specimens, not only degenerative changes but also destruction of cancer nests caused by cell death were observed. The histological effects affected by short term endocrine treatment had no relation to the prognosis, but in the cases of stage D2, the pathological grade judged by post-therapeutic specimens were found to be useful for the prediction of prognosis.. Endocrine therapy induces remarkable pathological changes in prostatic cancer within a very short time after beginning treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Combined Modality Therapy; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms

Recently, there has been increased interest in the application of preoperative endocrine therapy prior to radical prostatectomy for locally advanced cancer in order to enhance surgical curability and increase survival. Between 1986 and 1993, 40 patients with prostate cancer were given endocrine therapy before radical prostatectomy. Fifteen patients had stage B2 disease and 25 stage C. The median duration of preoperative endocrine therapy was 3.8 months, and all the patients subsequently underwent radical prostatectomy, pelvic lymphadenectomy and castration. There was an average 25.5% (0-71.8%) decreases in the maximal cross-sectional area of the prostate gland as determined by transrectal ultrasonography. Twenty-four of 25 patients with elevated levels of serum prostate-specific antigen (PSA) showed normal values after preoperative endocrine therapy. Evaluation of treatment-related histological effects, divided into three grades, revealed that 17 patients had pronounced, 11 moderate and 12 poor or no regression. Thirteen of the 40 patients (33%) demonstrated pathological downstaging of disease status from the diagnosis made at the initial clinical examination. After a median follow-up period of 36 months (3-100 months), 36 of the 40 patients are disease-free; two died of cancer 43 and 50 months after surgery, respectively. These results suggest that preoperative endocrine therapy may play an important role in the management of locally advanced prostatic cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Chlormadinone Acetate; Diethylstilbestrol; Estramustine; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Lymph Node Excision; Male; Middle Aged; Neoplasm Recurrence, Local; Preoperative Care; Prostatectomy; Prostatic Neoplasms

From November 1984 to December 1993, 72 patients with newly diagnosed, stage C or D prostate cancer were treated with chemohormonal therapy consisting of CDDP, CPM, diethylstilbestrol diphosphate and orchiectomy. Forty-four of 72 patients (61%) had partial response 3 months after the initiation of the treatment. A good response rate was observed in prostate gland and tumor markers (63% and 81%), but the response rate was poor in bone and other soft tissure metastasis (17% and 18%). Subjective symptoms improved in 82% of the pain, 70% of the infravesical obstruction, 65% of the performance status, and 5% of the body weight. The 5-year survival rate was 66%. The prognosis of the patients with poorly differentiated carcinoma or high Gleason score tumor was poor. Survival rate was no different between stage C and D. Relapse occurred in 16 patients (22%) and tended to occur in the patients with poorly differentiated carcinoma, high Gleason score tumor, stage D2 or stable disease. The survival rate was better, and the relapse rate lower than in the 35 patients with hormonal treatment alone during the same period, but no significant difference was observed between the two groups.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Cyclophosphamide; Diethylstilbestrol; Humans; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Survival Rate

We evaluated the usefulness of hormonal therapy combined with UFT as initial treatment in comparison with hormonal therapy alone in 92 patients with Stage D2 prostatic cancer treated at the Department of Urology, Dokkyo University School of Medicine between 1974 and 1993. Twenty-six of these patients were treated with diethylstilbestrol diphosphate (DESP) and castration (hormonal therapy alone group), and 23 patients were treated with UFT, DESP and castration (UFT combined therapy group). The 5-year survival rates calculated with Kaplan-Meier's method in the hormonal therapy alone group and the UFT combined therapy group were 34.6 % and 38.3%, respectively. However, the 3-year survival rates of pathologically poorly differentiated adenocarcinoma in these groups were 30.0% and 50.0%, respectively. Based on these results, it was suggested that UFT administration combined with hormonal therapy is useful for pathologically poorly differentiated adenocarcinoma in Stage D2 prostatic cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Survival Rate; Tegafur; Uracil

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diethylstilbestrol; Doxorubicin; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone-resistant disease leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement: Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Diethylstilbestrol; Drug Resistance; Humans; Infusions, Intravenous; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

At the Second Tokyo National Hospital, treatment of patients with prostatic cancer was carried out under the same protocol over 12 years. The mean age of the patients was 73.6 years, and 50% of them fell into the Stage D category. As the initial treatment, hormonal therapy consisting primarily of diethylstilbestrol diphosphate (DES-P) was given to 93.8% of the patients, and the effectiveness of the initial treatment was observed in 87.4% of them. The pre-treatment tumor marker value was high in 65.6% of the patients, and reverted to within normal limits after treatment in 51.3% of them. Relapse was observed in 15.0% of the patients. Side effects of hormonal therapy were observed in 20.7% of the patients, and the side effects resulted in death in 1.3% of them. Throughout the duration of the study, 34.4% of the patients resulted in death; 18.8% of these deaths related to cancer and 13.1% of them to other causes. The 5-year survival rate of all patients was 68.1%, and the 10-year survival rate was 52.7%. DES-P which is the primary drug in the protocol employed at our institution was well tolerated in the patients with minimal side effects when given appropriately and was believed to be an extremely effective drug in the treatment of prostatic cancer in Japan.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Survival Rate

A randomized clinical trial of neoadjuvant endocrine therapy followed by either surgery or irradiation and a resumption of endocrine therapy for stages B2 and C prostate cancer has been in progress since 1989. A hundred patients entered the trial between 1989 and 1993, and 95 cases were evaluated. Forty-six patients received surgery and 49 were treated with irradiation. Neoadjuvant endocrine therapy for two months resulted in prostate shrinkage and prostate specific antigen lowering. Except for two patients, one dying of a progression of disease and the other of another concurrent cancer, all are alive with an average follow-up term of 25 (range 3-53) months. The good prognostic results obtained from both treatment groups at present seem to be due in part to the neoadjuvant endocrine therapy; but in order to reach a final conclusion further comparisons need to be made.

Topics: Aged; Antineoplastic Agents; Chemotherapy, Adjuvant; Diethylstilbestrol; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Radiotherapy Dosage; Registries; Remission Induction

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer, independently of palliative radiotherapy. The evolution to hormone-resistance status leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol diphosphate) has been suggested to circumvent hormone-resistance and to induce a direct cytotoxic effect. Sixteen patients with hormone-resistant prostate cancer were treated by continuous infusion of high-dose fosfestrol according to two schedules: 10 patients were included in a phase I trial of a daily escalating dose from 1.5 g/d to 4.5 g/d for 7 to 10 days. Six other patients were uniformly treated by 4 g/d for 3.5 h for 5 days. Between each course, patients received orally 300 mg/d fosfestrol and 200 mg/d salicylic acid. The mean age was 65 years (range 51-75). Mean number of courses was two (extremes 1-7). Toxicities: reversible weight gain was observed in five patients. One patient presented a pulmonary edema which was resolved immediately after diuretics. One patient and 9 patients respectively experienced grade III and II (OMS) nausea and vomiting. Transient perineal pruritus occurred in 5 patients. Responses: 15 patients were evaluable (one early death occurred on day 3 from tumor progression complicated by an intravascular coagulation disease). There were four objective stabilizations (NPCP criteria) lasting 2 m, 2 m, 5 m and 10 m respectively. Subjective improvement of pain was observed in five other patients. There was more than 50% reduction of PSA in eight patients. High-dose fosfestrol seems to have some objective activity with moderate toxicity and warrants further investigation.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms

From 1981 to 1989, 24 patients with newly diagnosed metastatic prostate cancer received hormone chemotherapy consisting of orchiectomy, diethylstilbestrol diphosphate and cisplatin. The survival rates were compared with those of 17 metastatic prostate cancer patients who were treated with hormone therapy alone. The five-year survival rates for the hormone chemotherapy group and the hormone therapy group were 64.6% and 29.4%, respectively. Based on our findings, it seems likely that hormone chemotherapy is one of the most effective treatments for patients with newly diagnosed metastatic prostate cancer.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Diethylstilbestrol; Follow-Up Studies; Humans; Male; Orchiectomy; Prostatic Neoplasms; Survival Rate; Time Factors

Between August, 1986 and August, 1992, 16 combination chemotherapies with etoposide (100 mg/body, day 1-5), ifosfamide (50 mg/kg, day 1, 3, 5), peplomycin (5 mg/body, day 1-5) were performed on 13 patients with endocrine therapy-relapsed advanced prostatic cancer. Seven trials were performed on 5 patients who received DESP (diethylstilbestrol diphosphate) (500 mg/body, day 1-5) with the chemotherapy. In 9 trials performed on 9 patients who did not receive DESP, there was no response case. In 7 trials with DESP, one trial had a partial response (PR) (14%) and 4 remained objectively stable (stable) (57%). As to adverse effects, myelosuppression was observed in all trials but there was no lethal toxicity. The one-year survival rate of these patients treated with the chemotherapy alone and combined DESP were both about 20%. Therefore we should find a more effective treatment for endocrine relapsed prostatic cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Drug Administration Schedule; Etoposide; Humans; Ifosfamide; Male; Middle Aged; Orchiectomy; Peplomycin; Prognosis; Prostatic Neoplasms; Survival Rate

The initial treatment of advanced-stage prostate cancer is total androgen deprivation. Autonomous proliferation of primarily or secondarily hormonal unresponsive cells may explain the development of hormone-refractory status. The median survival of patients with hormone-resistant disease is short; there is no standard regimen of chemotherapy.. Fosfestrol or diethylstilbestrol diphosphate and its metabolites have cytotoxic activity in hormone-refractory prostatic cell lines. Pharmacokinetic studies have shown that fosfestrol metabolites have a short half-life that supports the use of long-term infusion in the clinic.. A review of the literature shows that high-dose fosfestrol induces no objective response, a greater than 50% tumor marker decrease in 50% of patients, a subjective improvement in 75% of patients, and cardiovascular complications in 5% of patients. The median survival time of patients is 5 months after the onset of treatment.. An exact evaluation of the role of high-dose estrogens requires additional investigation.

Topics: Aged; Antineoplastic Agents; Diethylstilbestrol; Drug Resistance; Humans; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Tumor Cells, Cultured

From June 1984 to March 1988, patients with newly diagnosed stage D2 prostate cancer were treated with protocol 1. This comprised oral hormonal agents either diethylstilbestrol diphosphate (Honvan: 300 mg/day) or estramustine phosphate (Estracyt: 560 mg/day), or chlormadinone acetate (Prostal: 100 mg/day), plus intravenous cyclophosphamide (CPM, 0.5-1 g/m2) every 3-4 weeks. From May 1988, protocol 2 was used in a randomized study of castration alone versus castration plus intravenous methotrexate (MTX, 20 mg/m2) every 2 weeks. Forty-nine of 53 patients who underwent the two protocols were evaluable for the response. The response rates according to the NPCP criteria were 92% (11/12) for Honvan, 100% (9/9) for Estracyt, 78% (7/9) for Prostal and castration plus MTX, and 80% (8/10) for castration alone. There were no significant differences among these treatments. The median response duration and survival time (months) were 16 and 44, respectively, for Honvan, 19 and 37 for Estracyt, 12 and 43 for Prostal, 11 and 15 for castration plus MTX, and 13 and 13 for castration alone. The short survival times of the castration alone and castration plus MTX groups were due to a short follow-up period. There were no statistical differences among the oral hormonal agent plus CPM groups. However, the 2-year survival rate (Kaplan-Meier method) was higher in the CPM and MTX groups than in the castration alone group. Survival was longer in the good performance status (P.S.) group than the poor P.S. group (p less than 0.05 by Wilcoxon test) and in the responders than the non-responders (p less than 0.01). Side effects were not excessive in the chemotherapy groups and patient compliance was good.

Topics: Administration, Oral; Aged; Aged, 80 and over; Castration; Chlormadinone Acetate; Combined Modality Therapy; Cyclophosphamide; Diethylstilbestrol; Drug Therapy, Combination; Estramustine; Humans; Infusions, Intravenous; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Survival Rate

Fifty-one patients with stage D prostate cancer, who had failed primary hormone treatment, were treated with diethylstilbestrol diphosphate (DES-DP) 1.5 g 24 hr intravenous infusion from day 1 to day 7 (group A). In group B, patients were treated with DES-DP as in A, plus vindesine (VND) 3 mg/m2 intravenously on days 8, 15, and 22. Cycles were repeated every 28 days for six consecutive cycles. All 51 patients were evaluable for response, toxicity, time to progression, and survival. Pretreatment clinical and laboratory characteristics were comparable. The National Prostatic Cancer Project Criteria were used for evaluation. A minimum of two cycles were required for evaluation of response. No complete response was seen. In group A, 9 "partial response" and 7 "no change" (80%), and in group B, 11 "partial response" and 12 "no change" (74%) were registered. Median survival time was 40 weeks. Toxicity ranged from mild to moderate. DES-DP + VND seemed to improve duration of objective response compared to DES-DP alone, but the difference was not significant.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Diethylstilbestrol; Estrogens; Humans; Infusions, Intravenous; Male; Middle Aged; Prostatic Neoplasms; Survival Rate; Vindesine

The present study was designed to investigate the efficacy of various combinations of chemotherapeutic agents in the treatment of prostatic cancer in a group refractory to antiandrogenic therapy (Group 1) and in a previous untreated group (Group 2). Therapeutic combinations of Estracyt (E) + Peplomycin (P) + Doxorubicin (Do) and P + Do + 5 FU (F) in Group 1 and E + P, Honvan (Ds) + P and E in Group 2 were carried out. The main objectives of this study were estimations of the efficacy of E and P in relation to the refractory cases of Group 1 and the efficacy of the combination E + P, in Group 2. This is the first such prospective, randomized, controlled study to be carried out in Japan in relation to prostatic cancer. The results obtained in the present study indicated that chemotherapeutic regimens including E provide some enhanced efficacy, but that the efficacy with regard to refractory cases is poor (23.1-27.3%), as has been reported of studies conducted in the USA and Europe. With regard to previously untreated cases, the E + P regimen achieved a relatively higher response rate than the other treatments (72.7 vs 44.5 or 50.0%). In the comparison of survival times and survival curves, there were no statistically significant differences among the various treatment subgroups. A comparison of survival curves revealed the interesting finding that the PAP-related response showed a clear correlation to the survival curves of Group 2 patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Diethylstilbestrol; Doxorubicin; Estramustine; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Staging; Nitrogen Mustard Compounds; Peplomycin; Prospective Studies; Prostatic Neoplasms; Random Allocation

The National Prostatic Cancer Project from 1982 to 1985 evaluated several treatments for metastatic prostatic cancer patients who had a history of prior radiotherapy and were refractory to hormone manipulation. The treatments studied were megestrol acetate (Megace), Megace plus diethylstilbestrol (DES), diethylstilbestrol diphosphate (Stilphostrol), and streptozotocin. While the four treatment arms did not differ significantly with respect to survival, there was a small but significant difference in progression-free survival among the treatment groups. These patients are difficult to treat and have many secondary problems, and perhaps future studies of current and new agents should focus more on subjective and other secondary benefits for them.

Topics: Clinical Trials as Topic; Combined Modality Therapy; Diethylstilbestrol; Humans; Male; Megestrol; Megestrol Acetate; Prostatic Neoplasms; Random Allocation; Streptozocin

The influence on the specific cell-mediated immunity (CMI) of the carcinoma of the prostate gland by the contra-sexual hormone therapy with Cytonal, Estrazyt and Turisteron is controlled. For this purpose the macrophage-electrophoresis-mobility test on the basis of allogenic tumour-associated antigen of the carcinoma of the prostate gland is used. As a result the use of Cytonal at least in the dosage hitherto used is no longer worth being advocated. Turisteron and Estrazyt, respectively, taking into consideration their pharmacokinetics and indication, prove to be immunologically optimal and without hesitation, respectively. Turisteron is the basic therapeutic in the androgen-dependent carcinoma of the prostate gland. Estrazyt should be reserved to primarily and secondarily hormone-refractory tumours. For the application of Estrazyt an additive immune stimulation seems to be worth taking into consideration.

Topics: Aged; Antineoplastic Agents; Clinical Trials as Topic; Combined Modality Therapy; Diethylstilbestrol; Estramustine; Ethinyl Estradiol; Humans; Immunity, Cellular; Macrophages; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation

Due to an advanced prostatic carcinoma 166 patients were given a massive dose of oestrogen over a period of 10 days (6 g Honvan i.v.). A retrospective comparison of a control group of 94 patients without prophylaxis against thrombosis and a control group of 36 patients having received Heparin-Dihydergot did not show a significant difference of cardiovascular complications. Therefore, further 36 patients received a thrombocyte aggregation inhibitor (Godamed) as prophylaxis against embolic thrombosis. At the same time lung perfusion scintigraphy (99m Tc-Microspheres) was made directly before and after oestrogen therapy. Clinically and lung scintigraphically there was no different thromboembolic incidence compared to the patients given a Heparin-Dihydergot prophylaxis.

Topics: Aged; Anticoagulants; Antineoplastic Agents; Aspirin; Clinical Trials as Topic; Diethylstilbestrol; Dihydroergotamine; Drug Combinations; Glycine; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Platelet Aggregation; Prostatic Neoplasms; Retrospective Studies; Thromboembolism

The objective of the current research work was to fabricate a fosfestrol (FST)-loaded self-nanoemulsifying drug delivery system (SNEDDS) to escalate the oral solubility and bioavailability and thereby the effectiveness of FST against prostate cancer.. 3. Using different ratios of surfactant and co-surfactant (Km) a pseudo ternary phase diagram was constructed. Thirteen liquid nano emulsion formulations (LNE-1 to LNE-13) were formulated at Km = 3:1. LNE-9 exhibited a higher % transmittance (99.25 ± 1.82 %) and a lower self-emulsification time (24 ± 0.32 s). No incompatibility was observed in FT-IR analysis. Within 20 min the solidified FST loaded LNE-9 (FSTNE) formulation showed almost complete drug release (98.20 ± 1.30 %) when compared to marketed formulation (40.36 ± 2.8 %), and pure FST (32 ± 3.3 %) in 0.1 N HCl. In pH 6.8 phosphate buffer, the release profiles are found moderately higher than in 0.1 N HCl. FSTNE significantly (P < 0.001) inhibited the PC-3 prostate cell proliferation and also caused apoptosis (P < 0.001) compared to FST. The in vitro Caco-2 cell permeability study results revealed 4.68-fold higher cell permeability of FSTNE than FST. Remarkably, 4.5-fold rise in bioavailability was observed after oral administration of FSTNE than plain FST.. FSTNE remarkably enhanced the in vitro anticancer activity and Caco-2 cell permeability, and in vivo bioavailability of FST. Thus, FST-SNEDDS could be utilized as a potential carrier for effective oral treatment of prostate cancer.

Topics: Administration, Oral; Biological Availability; Caco-2 Cells; Drug Delivery Systems; Drug Liberation; Emulsions; Humans; Male; Nanoparticles; Particle Size; Prostatic Neoplasms; Solubility; Spectroscopy, Fourier Transform Infrared; Surface-Active Agents

We conducted the present study to evaluate the safety profile and therapeutic value of a combination of etoposide and fosfestrol for treatment of hormone-refractory prostate cancer (HRPC).. Forty patients with HRPC were included in the study. The median age was 71 years (range, 50-86 years), the Gleason's score ranged from 5 to 10, and the median prostate-specific antigen level was 62.6 ng/mL (range, 4.738-30789 ng/mL). The patients received oral etoposide 25 mg/d and fosfestrol 300 mg/d.. The response rate in terms of measurable disease, serum prostate-specific antigen level, and overall evaluation was 36.8% (CR: 18.4%; PR: 18.4%), 80% (CR: 55%; PR: 25%), and 40% (CR: 20%; PR: 20%) with a median duration of response of 13.6, 13.5, and 13.5 months, respectively. An objective clinical response for overall evaluation was shown by 90% (CR: 20%; PR: 20%; SD: 50%) of the patients, with a median response duration of 15.7 months; 16 patients (40%) are currently alive without recurrence after a median follow-up period of 21.2 months. The overall survival and progression-free survival was 30.5% and 28.8% at 40 months, respectively. No grade III toxicities occurred in any of the patients. Serial measurements in 34 patients using the Functional Assessment of Cancer Therapy-Prostate showed a significant improvement in quality of life as a result of the therapy.. The combination of oral etoposide and fosfestrol is active in patients with HRPC. The regimen is tolerable and has a significant impact on quality of life as measured by the Functional Assessment of Cancer Therapy-Prostate in a limited sample of patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Etoposide; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Salvage Therapy; Survival Analysis

A 67-year-old man was diagnosed as having prostate cancer with bone metastasis by his personal physician in 2002. He received androgen deprivation therapy, and then prostate specific antigen (PSA) declined to an undetectable level over the short term. In 2004, PSA gradually became elevated despite androgen deprivation therapy. Although secondary hormonal therapy was started, PSA continued to increase. With the complaint of back pain, he consulted our clinic. On initial examination at our clinic, PSA was 390.3 ng/ml and alkaline phosphatase (ALP) was 2,338 IU/L. He was administered diethylstilbestrol diphosphate (DES-DP) and zoledronic acid intravenously and then PSA declined to an undetectable value again. In the course of the administration, liver enzymes were elevated and DES-DP administration was discontinued. However, with continued administration of zoledronic acid, PSA remained undetectable despite a 5-month interruption of DES-DP treatment. Thereafter, back pain completely disappeared.

Topics: Aged; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Bone Neoplasms; Diethylstilbestrol; Diphosphonates; Drug Therapy, Combination; Humans; Imidazoles; Injections, Intravenous; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Zoledronic Acid

Neoadjuvant hormone therapy remains a controversial issue in spite of multiple studies having been performed.. We performed short-term (10 days) treatment with diethylstilbestrol (DES) in 30 patients with stages T2 or T3 prostate cancer (PCa). All the patients underwent needle core prostate biopsy before and radical prostatectomy within a month after the start of the endocrine therapy. The histological effects in PCa and the changes in morphological and clinical parameters and their association were elucidated.. Serum PSA (P < 0.001), Ki-67 PI (P = 0.022), and AR (P = 0.002) expression decreased after the treatment. An obvious effect (Grade 1-3) of endocrine treatment was seen in 11 of 30 patients and was associated with a prominent PSA decrease (P = 0.0274) and with older age (P = 0.0026). Pre-treatment specimens from a group without any effects of endocrine therapy had a higher frequency of Bcl-2 positivity (57.9%) compared to the group of Grade 1-3 effects (27.3%). Prostatectomy specimens presented with significantly higher AI in Bcl-2 negative cases (P = 0.0029) and pre treatment Bcl-2 was associated with a higher AI in Grade 1-3 patients (P = 0.0393).. Older age is a predictor of histological effects in short-term hormone treatment of PCa. A lower Bcl-2 in biopsy specimens presented more frequently in the patients who experienced a prominent effect of endocrine therapy, and it was also useful to predict a significantly higher AI in Grade 1-3 patients. Histological effects are also associated with the PSA decrease, reflecting the clinically meaningful shrinkage of tumors and a decrease of tumor burden.

Topics: Aged; Antineoplastic Agents, Hormonal; Apoptosis; Biopsy; Diethylstilbestrol; Drug Administration Schedule; Humans; In Situ Nick-End Labeling; Ki-67 Antigen; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Receptors, Androgen

We studied two cases of primary, hepatocellular carcinoma (HCC) that occurred following hormone therapy (estrogen therapy in one case and total androgen blockade therapy in another) for stage D2 prostate cancer. Prostate cancer is considered to be hormone-dependent, and androgens appear to be important hormonal factors. However, hepatocellular carcinoma has been shown to have both estrogen and androgen receptors, suggesting that this may be dependent on estrogen or androgen. Reported here are two unique cases of hepatocellular carcinoma in patients with prostate cancer; the pathogenesis of HCC in these patients was suspected to be related to diethylstilbestrol (DES) therapy and antiandrogen therapy for their prostate cancer.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Carcinoma, Hepatocellular; Diethylstilbestrol; Drug Administration Schedule; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasms, Second Primary; Prostatic Neoplasms

This study reports--for the first time--a capillary electrophoretic method for the determination of fosfestrol, a synthetic estrogen used in the treatment of metastatic prostate cancer. The effects of the carrier ion concentration, injected volume and applied voltage were studied and optimized. A 10 mM sodium tetraborate solution was selected as the carrier electrolyte solution, while the sample was injected hydrodynamically by applying a 20 mmHg vacuum for 1 s. The driving voltage was 30 kV and the absorbance of the analyte (peak height) was monitored at 240 nm. Under the above-mentioned conditions, the migration time of fosfestrol was 6.6 min. Linearity was achieved in the analyte range 3-150 mgL(-1) with the detection limit being 1 mgL(-1). The proposed method is adequately precise (s(r)=2.8% at 100 mgL(-1) fosfestrol, n=10) without the use of an internal standard and was applied to the determination of fosfestrol in a pharmaceutical formulation. The results obtained by the proposed method were in good agreement with those derived from the USP reference method.

Topics: Antineoplastic Agents, Hormonal; Chromatography, High Pressure Liquid; Diethylstilbestrol; Drug Industry; Electrophoresis, Capillary; Estrogens; Humans; Male; Models, Chemical; Pharmaceutical Preparations; Prostatic Neoplasms; Reproducibility of Results; Time Factors

To evaluate the role of Estrogens (Honvan) in the secondary hormonal manipulation of patients with hormone refractory prostate cancer (HRCP).. Twelve patients diagnosed as hormone refractory prostate cancer received intravenous estrogens for six days (Fosfestrol, a synthetic phosphorylated estrogen derivative), followed by a maintenance oral dose of 120 mg thrice daily as second line hormonal treatment. During the treatment they were given deep venous thrombosis prophylaxis. Their stage at initial presentation, primary treatment, mode of androgen ablation, prostate specific antigen (PSA) level, duration of remission prior of HRPC status, PSA doubling time before and after estrogen treatment were recorded. The morbidity and mortality of the treatment was also recorded. A drop in PSA of > 50% was classified as major responder. The drop of < 50% was defined as minor responders. Treatment failure was defined as a rise in PSA > the level prior to the start of treatment.. The mean age at diagnosis of prostate cancer was 66.6 + 5.4 years (range 57-73). At the time of initial diagnosis only 3 patients (25%) had localized disease and 9 (75%) had metastatic prostate cancer. Six patients each opted for surgical or medical castration (LHRH analogs) as the mode of androgen ablation. The mean initial PSA at diagnosis was 340 + 728.1 ng/ml (range 4.1-2375, Median 94). After development of HRPC, six patients (50%) had major response, four (33%) had minor response to estrogen administration. Two patients (17%) did not respond to estrogens. The mean PSA before receiving Fosfestrol was 60.5 + 82 ng/ml (range 0.013-246). The PSA (nadir) after treatment was 24.3 +/- 33.2 ng/ml (range 0.9-81.3). One patient developed gynaecomastia and one had congestive cardiac failure. Two patients died of non cancer related deaths and one patient died of cancer related death.. Synthetic estrogens are well tolerated, in-expensive agents and could be considered for palliative use against hormone resistant prostate cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antineoplastic Agents, Hormonal; Cohort Studies; Diethylstilbestrol; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Infusions, Intravenous; Male; Middle Aged; Pakistan; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Retrospective Studies; Survival Analysis; Treatment Outcome

Prostate is one of the most common sites of multiple primary cancer (MPC). We herein present two cases of prostate cancer associated with acute myeloid leukemia (AML) presenting as thrombocytopenia during endocrine therapy. After a diagnosis of prostate cancer (stage D2) was made, our patients received endocrine treatment with fosfestrol followed by a luteinizing hormone-releasing hormone (LH-RH) analogue and bicaltamide. Thrombocytopenia appeared 8 months and 10 months after the initiation of endocrine therapy, respectively. Because suspensions of bicaltamide resulted in further deterioration of thrombocytopenia, bone marrow aspirations were done with hematological examination revealing features of the M2 subtype of AML. Review of MPC with prostate cancer in the literature suggested that the combination of prostate cancer and AML was rare.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Diethylstilbestrol; Humans; Leukemia, Myeloid, Acute; Male; Neoplasms, Multiple Primary; Prostatic Neoplasms; Thrombocytopenia

Estrogen has been highly evaluated as one of the most potent endocrine agents for the treatment of prostate cancer. Unfortunately, a high risk of cardiovascular complications is a clinically important adverse effect of estrogen therapy, and occasionally the complications are fatal. In recent years a high incidence (55%) of thrombotic events has been reported in patients with congenital protein S (PS) deficiency. The aim of this study is to determine the relationship between cardiovascular complications of estrogen therapy and anticoagulant factor levels in the serum of patients with prostate cancer.. Study 1 employed 99 patients with prostate cancer: 39 were untreated, 25 were treated with LH-RH agonist therapy alone, and 35 were treated with oral diethylstilbestrol diphosphate (DESdP) 300 mg per day. We measured the serum levels of anticoagulant factors, parameters antithrombin III (ATIII), protein C (PC), PS, coagulant and fibrinolytic factors in all patients. In study 2, the adverse effects of DESdP therapy on the serum levels of anticoagulant factors were examined in 8 patients with advanced prostate cancer.. In study 1, the ATIII and PS levels of the patients treated with estrogen therapy were significantly lower than those in either the untreated patients or the patients treated with an LHRH agonist alone. Especially, both PS antigen (51.5 +/- 16.0%) and PS activity (42.9 +/- 16.0%) were markedly lower in estrogen-treated patients than in the untreated patients (102 +/- 20.8%, 100.6 +/- 20.7%, respectively) or the patients treated with an LH-RH agonist alone (97.9 +/- 16.8%, 91.5 +/- 17.7%, respectively, both p < 0.0001). PS was decreased to below the normal lower limit of normal in 82% (24/35) of the patients on estrogen therapy. In study 2, all 8 cases showed a significant decrease in PS after DESdP therapy.. Our results showed that the PS levels in the oral DESdP group were almost the same as in patients with congenital PS deficiency. We conclude that decreased PS may play a role in the development of cardiovascular complications in prostate cancer patients on estrogen therapy.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antithrombin III; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Neoplasms; Protein C; Protein S

Many types of chemotherapy are now being attempted all over the world for hormone-refractory prostate cancer (HRPC) patients, and prostate-specific antigen (PSA) reduction in almost half of the treated patients has been reported. However, only a few studies have reported the response of bone metastasis. The authors report a patient with HRPC who obtained complete regression of bone metastases on super bone scan by biochemical modulation (BM), dexamethasone, and endocrine therapy.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Bone Neoplasms; Cisplatin; Dexamethasone; Diethylstilbestrol; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Neoplasm; Follow-Up Studies; Hormones; Humans; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Risk Assessment; Tegafur; Tomography, X-Ray Computed; Treatment Outcome; Uracil

Topics: Administration, Oral; Antineoplastic Agents, Hormonal; Belladonna Alkaloids; Diethylstilbestrol; Dose-Response Relationship, Drug; Drug Combinations; Ergotamines; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Injections, Intramuscular; Male; Medroxyprogesterone Acetate; Megestrol Acetate; Methysergide; Middle Aged; Phenobarbital; Prostatic Neoplasms

Estrogen administration is known to increase serum triglyceride concentrations. This study measured changes in lipoproteins of patients with prostate cancer treated with estrogen to determine whether the increased triglyceride concentrations are associated with atherogenic lipoprotein patterns.. Fifteen patients (52-87 years) with histologically diagnosed prostate cancer received diethylstilbestrol diphosphate (250 mg/day). Serum samples were collected before and after 1 and 2 weeks of treatment. Cholesterol and triglyceride profiles of major lipoproteins were determined by HPLC, remnant-like particle cholesterol and triglyceride concentrations by an immunoseparation technique, and apolipoproteins by immunologic methods.. Estrogen treatment induced a 63.3% increase in total triglyceride concentrations, which occurred in all major lipoprotein classes with significant increases in HDL-triglycerides (130.4%), LDL-triglycerides (60.7%) and VLDL-triglycerides (56.2%). HDL-cholesterol increased significantly by 26.8%, while LDL-cholesterol decreased (15.6%). Remnant-like particle triglyceride concentrations also increased significantly by 77%, whereas remnant-like particle cholesterol concentrations remained unchanged. Apolipoproteins A-I and A-II increased; apolipoprotein E and Lp(a) decreased.. The techniques used here conveniently demonstrated that short-term estrogen treatment in prostate cancer patients resulted in triglyceride enrichment of all major lipoprotein classes but did not induce changes in the lipoprotein profiles generally recognized as increasing risk for cardiovascular disease, except for the elevation of plasma triglyceride and remnant-like particle triglyceride.

Topics: Aged; Aged, 80 and over; Apolipoproteins; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Diethylstilbestrol; Humans; Immunosorbent Techniques; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Particle Size; Prostatic Neoplasms; Triglycerides

Patients with prostate cancer generally respond to androgen withdrawal therapy, but progression to androgen-independence is frequently observed later. To examine whether pretreatment serum androgen status could predict disease progression in metastatic prostate cancer, pretreatment serum testosterone, histological grade, extent of bony metastasis, serum prostate-specific antigen (PSA) response to hormone therapy, and prognosis of the 40 patients with untreated metastatic prostate cancer who received endocrine therapy were evaluated. Although there were no differences in age, pretreatment PSA level, extent of bony disease and histological grade between patients with normal testosterone and those with low testosterone, PSA response after endocrine therapy was better in normal testosterone group. There was a significantly longer interval to disease progression in patients with normal testosterone than in those with low testosterone. The patients with metastatic prostate cancer with low serum testosterone were in the high risk group of worse response to endocrine therapy. Additional therapy might be considered in those patients.

Topics: Aged; Aged, 80 and over; Anilides; Antineoplastic Agents, Hormonal; Bone Neoplasms; Chlormadinone Acetate; Diethylstilbestrol; Disease Progression; Flutamide; Gonadotropin-Releasing Hormone; Humans; Japan; Male; Middle Aged; Neoplasms, Hormone-Dependent; Nitriles; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Statistics, Nonparametric; Testosterone; Tosyl Compounds

To examine the efficacy and toxicity of a moderate dose (250 mg/day) of diethylstilbestrol diphosphate (DES-DP) intravenously administered to patients with hormone refractory prostate cancer (HRPC) as well as the influence of this agent on the endocrine system.. Sixteen patients with HRPC were treated with a daily intravenous injection of 250 mg of DES-DP for 28 days. Eastern Cooperation Oncology Group (ECOG) performance status and pain score were used for subjective evaluation and PSA was used for objective evaluation. Testosterone, free testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were used for hormonal parameters.. Fourteen patients were eligible. The mean patient age was 75.2 years. With respect to the ECOG pain score, 5 patients scored 1 or higher, in 4 patients, the pain completely disappeared, and in 1 patient, the pain score improved from 4 to 1. The PSA level decreased significantly from 528 +/- 556 ng/ml (mean +/- SD) to 154 +/- 197 ng/ml. The DHEA level was not changed during DES-DP administration. The DHEA-S level decreased significantly from 882 +/- 430 ng/ml to 480 +/- 236 ng/ml. Testosterone and free testosterone were in the castration level before and during the treatment. Toxicity was minimal. None of the patients developed cardiovascular disorder.. A moderate dose (250 mg/day) of DES-DP decreased PSA levels and relieved pain without causing serious toxicity in patients with HRPC. It is suggested that the mechanism of the DES-DP effect on the decrease in PSA and pain relief involves a decrease in DHEA-S.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Injections, Intravenous; Male; Middle Aged; Prostatic Neoplasms; Testosterone

Fosfestrol drip infusion therapy is an available endocrinotherapy for prostate cancer. But since there have been few reports of its use in chronic dialysis patients, the pharmacokinetics of fosfestrol in these patients remains unclear. We conducted fosfestrol drip infusion therapy as an induction therapy in chronic hemodialysis patients with prostate cancer.. Two male patients were included in this study. One was a 68-year-old man who had been in hemodialysis for 15.7 years and had stage B2 prostate cancer. The other was a 74-year-old man who had been in hemodialysis for 4.4 years and had stage C prostate cancer. A total of 250 mg of fosfestrol was dissolved in 250 mL of 5% glucose solution and administered by drip infusion. The drug was given subcutaneously during 14 consecutive days and a luteinizing hormone-releasing hormone agonist was injected on day 15.. Serum fosfestrol levels increased rapidly after the drip infusion was started and remained at high levels during infusion, but fell quickly after the treatment ended. Diethylstilbestrol (DES) was also detected in blood after the infusion was started and its levels peaked when infusion ended. But on the next day, neither fosfestrol nor DES were detected in the blood of the patients. Moreover, neither fosfestrol nor DES was detected in the blood of the two patients before administering fosfestrol on day 15. Fosfestrol was quickly eliminated from the blood after hemodialysis was started, while DES remained in the blood during hemodialysis. The adverse reactions were mild hepatic dysfunction and gynecomastia.. Fosfestrol drip infusion therapy appeared to be safe as an endocrinotherapy for prostate cancer in chronic hemodialysis patients.

Topics: Aged; Area Under Curve; Diethylstilbestrol; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Prostatic Neoplasms; Renal Dialysis; Treatment Outcome

A 62-year-old man was admitted to our hospital because of urinary retention. A digital rectal examination revealed an enlarged, elastic, and hard prostate with an irregular surface. Prostatic biopsy was done and the pathological diagnosis was moderately differentiated adenocarcinoma. He was diagnosed as stage D2 by bone scan and MRI. We gave him 250 mg of fosfestrol intravenously for 13 days. Afterward, he underwent orchiectomy castrate and was given flutamide for two years. His condition has improved and he has experienced no relapse.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents; Diethylstilbestrol; Flutamide; Humans; Male; Middle Aged; Prostatic Neoplasms

Although not clearly defined, 'hormone refractory' prostate cancer implies disease progression after orchiectomy +/- antiandrogens. Patients in this setting are usually offered chemotherapy protocols which often lead to significant toxicity and expense. In search of a well-tolerated, active, third-line treatment, we have attempted to prolong hormonal maneuvers by using low-dose estrogen therapy.. Thirty-eight patients with evidence of disease progression (as indicated by 2 consecutively rising PSA determinations) after > or = 2 hormonal treatments (including surgical or chemical orchiectomy and a median of 3 prior treatment lines) received fosfestrol 100 mg t.i.d. per os in a continuous schedule until the appearance of progressive disease or excessive toxicity. Response was assessed by serial PSA levels. Complete response (CR) was defined as normalisation and partial response (PR) as a > or = 50 decrease of PSA levels for longer than one month. The median duration of prior treatment was 20 months and the median PSA at fosfestrol start was 126 ng/ml (range 8-12,800); symptoms (pain) were present in 73% of patients.. CR + PR were observed in 79% (95% confidence interval: 66%-92%). The median time to progression was seven months. Pain remained stable or improved in 34% and 53%, respectively, of symptomatic patients with PSA response. Toxicity included worsening of gynecomastia, peripheral edema, and deep vein thrombosis (8%). No treatment-related deaths occurred. Uni- and multivariate analyses failed to identify predictive factors for response. PSA response was associated with significantly longer survival (13 vs. 7 months, P < 0.05 by Mantel-Haentzel).. FOSF produces high rates of PSA-determined and symptomatic response in 'hormone-refractory' prostate cancer. Toxicity and ease of administration compare favorably with those reported for CHT regimens used in this setting. The role of estrogens in prostate cancer should be redefined.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Confidence Intervals; Diethylstilbestrol; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Survival Rate

Estimates of volume-weighted mean nuclear volume (MNV) are the only means by which unbiased estimates of three-dimensional parameters can be obtained from single two-dimensional sections without any assumptions. We have reported that for prostate cancer estimates of MNV are prognostically equal or superior to morphological grading of malignancy, such as Gleason score (GS), and in particular, that MNV proved to be a meaningful predictor of prognosis for patients with clinically localized tumors. However, all previous studies were conducted on patients treated conservatively, and no authors have tested whether estimates of MNV can predict the prognosis of patients treated with radical prostatectomy.. A retrospective prognostic study of 52 patients with clinically localized prostate cancer diagnosed at three Hospitals in Shizuoka Prefecture, Japan (Shizuoka City Hospital, Shizuoka Prefectural Hospital and Shimada Municipal Hospital) and treated by radical prostatectomy was performed. Twenty of these patients were treated with hormone therapy before radical prostatectomy. Unbiased estimates of MNV were compared with clinical stage, histological grading according to GS and neo-adjuvant hormone therapy with regard to the prognostic value.. MNV was significantly correlated with pathological T stage, but was not significantly correlated with the presence or absence of lymph node metastasis. Univariate analysis revealed that MNV correlated significantly with progression-free survival (p = 0.0116). Multivariate analysis revealed that MNV (p = 0.0115) and GS (p = 0.0275) were two significant independent predictors of progression-free survival.. The results of the present study suggest that MNV and GS are powerful independent predictors of prognosis for prostate cancer treated with radical prostatectomy. We recommend estimates of MNV as a supportive method to the histological grading for patients with prostate cancer.

Topics: Antineoplastic Agents; Cell Nucleus; Diethylstilbestrol; Disease Progression; Gonadotropin-Releasing Hormone; Humans; Male; Multivariate Analysis; Neoadjuvant Therapy; Predictive Value of Tests; Prognosis; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Survivors; Treatment Outcome

A 59-year-old man was admitted to our hospital because of muscular pain, weakness, and anorexia. He had been treated with 600 mg/day of fosfestrol, a synthetic estrogen, for 10 years for prostatic carcinoma. Endocrinological studies demonstrated adrenocortical insufficiency due to inadequate ACTH secretion. After initiation of glucocorticoid replacement therapy, his symptoms subsided rapidly. To our knowledge, an association between estrogenic agents, including fosfestrol, and secondary adrenocortical insufficiency has not been previously reported. Physicians who treat patients with long-term and high-dose strong estrogenic agents should be cautious about the possible emergence of secondary adrenocortical insufficiency.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Antineoplastic Agents; Diethylstilbestrol; Humans; Hydrocortisone; Male; Middle Aged; Prostatic Neoplasms

The objective of this study was to elucidate the mechanism underlying the further suppression of serum testosterone (T) by diethylstilbestrol diphosphate (DES-DP) in patients with prostate cancer refractory to hormonal treatment. These patients received an LHRH agonist with or without a non-steroidal androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, cortisol, aldosterone before and during intravenous administration of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration suppressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminated free T (p=0.04) and E2 (p=0.04) from serum, while reducing serum DHEA-S to approximately two-thirds of the pretreatment level (p=0.03). In contrast, serum levels of SHBG (p=0.02) and cortisol (p=0.02) were markedly increased after DES-DP administration. The latter had no significant effect on serum levels of LH, DHT, ACTH, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, DHEA, androstenedione, or aldosterone. The results suggest that the potent suppression of circulating total T by DES-DP is caused, in part, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patients, high-dose DES-DP treatment completely suppressed the serum level of free T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatment require further elucidation.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Chlormadinone Acetate; Dehydroepiandrosterone Sulfate; Diethylstilbestrol; Drug Resistance, Neoplasm; Estradiol; Follicle Stimulating Hormone; Goserelin; Hormones; Humans; Hydrocortisone; Leuprolide; Male; Middle Aged; Progesterone Congeners; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Testosterone

In the light of a case of left orbital metastasis, constituting the presenting sign of prostatic cancer in a 60-year-old man, the authors emphasize the rarity of this site, despite the high frequency of bone metastases in this disease. They discuss the diagnostic methods and stress the need for urgent treatment to save ocular function.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Emergencies; Goserelin; Humans; Injections, Intravenous; Male; Methylprednisolone Hemisuccinate; Middle Aged; Orbital Neoplasms; Prostatic Neoplasms; Vision, Ocular

Diethylstillbestrol (DES) and diethylstilbestrol diphosphate (DESdP) are effective agents for the treatment of advanced prostate cancers. Tumor-inhibiting effects of DES and DESdP are presumed secondary to suppression of androgen production in vivo. Little is known, however, about the direct cellular mechanisms of the tumor inhibition. Estrogens have been reported not only to stimulate growth but also to disrupt microtubule formation in prostate cancer cells.. The study was designed to examine and compare mechanisms of in vitro growth inhibition of DES and DESdP in human androgen-insensitive prostate cancer cells (DU145, 1-LN, and PC-3) and human androgen-sensitive prostate cancer cells (LNCaP) and to examine estrogen receptor modulation of such effects.. The cytotoxic effects of DES and DESdP were examined in vitro by use of a standard microculture tetrazolium assay to quantitate numbers of viable cells. Immunofluorescence microscopy, DNA fragmentation analysis, and fluorescence flow cytometry were used to investigate microtubules, the induction of apoptosis, and changes in cell cycle distribution. The degree of estrogen receptor positivity of untreated and treated cells was determined by immunohistochemistry and quantitative image analysis.. LD50 levels (the dose at which 50% of cells are no longer viable) in the concentration range of 19-25 microM were observed for both DES and DESdP in all cell lines examined. DESdP-induced growth inhibition was found to be dependent on heat-labile phosphatases present in fetal calf serum. DES-induced cytotoxicity was not affected by the presence of 17 beta-estradiol, and it was not dependent on the presence of estrogen receptor. Estrogen receptor-positive cells and estrogen receptor-negative cells were equally responsive to DES. PC-3 cells stained with fluorescent anti-tubulin, phalloidin (actin stain), and 4',6-diamidino-2-phenylindole (DNA stain) showed no inhibition of microtubules or actin filaments but revealed the presence of apoptotic bodies in the nuclei. Fluorescence flow cytometry of nuclear DNA content of propidium iodide-stained nuclei from androgen-insensitive prostate cancer cells treated with 15 or 30 microM DES or DESdP revealed an increase in relative numbers of hypodiploid (apoptotic) nuclei, a depletion of G1- and S-phase cells, and an accumulation of cells in G2/M phase. Conversely, androgen-sensitive cells contained a lower percentage of hypodiploid nuclei but no accumulation of cells in G2/M phase.. Direct cytotoxic effects of DES in prostate cancer cells are estrogen receptor independent and do not involve disruption of microtubule architecture but do involve the promotion of cell cycle arrest and apoptosis. These are the first data confirming direct cytotoxic effects of DES and DESdP in prostate cancer cells via an apoptotic mechanism. IMPLICATIONS. These results suggest that DES and DESdP have potential value as agents against androgen-insensitive prostate neoplasms through induction of an apoptotic cascade.

Topics: Antineoplastic Agents, Hormonal; Apoptosis; Diethylstilbestrol; DNA, Neoplasm; Dose-Response Relationship, Drug; Electrophoresis, Agar Gel; Estradiol; Flow Cytometry; Fluorescent Antibody Technique; Humans; Male; Microscopy, Ultraviolet; Prostatic Neoplasms; Receptors, Estrogen; Tumor Cells, Cultured

The objective of this study is to report the outcome of various treatments in patients who were newly diagnosed prostate cancer from May 1984 to December 1994, at a single institution.. A retrospective study was carried out in the 142 patients.. Total retropubic prostatectomy were performed in 52 patients (37%). The 5-year survival rates (Kaplan-Meier) in the patients with total prostatectomy were 89% in stage B (24), 86% in stage C (7), and 87% in stage D1 (17), respectively. Endocrine therapies (33) or endocrine therapies in combination with chemotherapies (37) as a initial therapy for stage D2 were performed. Among these therapies, endocrine therapy in combination with cyclophosphamide (700 mg/m2/4 weeks, i.v.) was superior to any of the other treatments in stage D2. The response rate, median response duration and median survival time in this combination therapy were 83%, 29 months and 49 months. The overall 3, 5, and 10-year survival rate in the 142 patients were 67%, 51% and 26%, respectively. The 5-year survival rates according to grade were 73% in grade 1, 45% in grade 2, 42% in grade 3, respectively.. The 5-year survival rates in pathological stage C and D1 patients who received adjuvant hormone and radiation therapy after radical prostatectomy were 86% and 87%. The most effective therapy for stage D2 was hormone in combination with cyclophosphamide. The response rate and median response duration were 83% and 29 months.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Chlormadinone Acetate; Combined Modality Therapy; Cyclophosphamide; Diethylstilbestrol; Humans; Male; Progesterone Congeners; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Survival Rate

The objective of this study is to evaluate the relationship between PSA value and prognosis of the patients with stage D2 prostate carcinoma.. Serum prostate specific antigen was analyzed in 61 patients with stage D2 prostate carcinoma submitted to hormone therapy.. The median values of PSA parameters were 77.6 ng/ml for the initial PSA, 91.8% for the maximal decrease, 2.7 ng/ml for the nadir, 1.1 months for the half-time time, 3.0 months for the time to nadir, 3.2 months for the doubling time after progression and 0.39 for the ratio of antemortem versus initial PSA. The median biochemical progression-free time was 15.0 months and the median actuarial survival after progression was 24.9 months. The progression-free time was significantly correlated with the normalization of PSA (p < 0.001) and the initial PSA of less than 100 ng/ml (p < 0.05), and the survival time after progression was significantly correlated with the doubling time (p < 0.05). The normalization of PSA was affected by initial value, maximal decrease rate and half-life time of PSA respectively, but not by the histological grade of the primary tumors. The doubling time was not correlated with these factors nor with the progression-free time.. The results show that the initial value, nadir level and doubling time of PSA can be used as prognostic parameters for prostatic carcinoma. Both the low ratio of premortem versus initial PSA, which may reflect an increase of stem cell fraction, and the PSA doubling time after relapse, which seems similar to or shorter than that of untreated cases, will indicate an aggressive potential of hormone-refractory tumors.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Combined Modality Therapy; Diethylstilbestrol; Disease Progression; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy

It is generally believed that signet-ring cell carcinoma (SRCC) of the prostate is a high-grade neoplasm with a poor prognosis. We report a case of a long-term survivor diagnosed with localized prostatic SRCC (T3N0M0), who has been alive without any clinical evidence of disease for 100 months after combination therapy which consisted of local irradiation and hormone administration. A posttreatment needle biopsy confirmed the pathological complete response.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Biopsy, Needle; Carcinoma, Signet Ring Cell; Diethylstilbestrol; Disease-Free Survival; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant

A 73-year-old male with low abdominal pain on urination and frequent urination was diagnosed as poorly differentiated adenocarcinoma of prostate. He received endocrine therapy with DESD and bilateral orchiectomy. This treatment was not effective, so he was given intra-arterial infusion chemotherapy with MTX, ADM and CDDP using the reservoir system. After 2 courses of this chemotherapy the regression rate was 75%, and the pathological examination after the chemotherapy revealed no cancer cells. There is no established chemotherapy for prostate cancer at present. Thus this case is very suggestive for the treatment of prostate cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diethylstilbestrol; Doxorubicin; Drug Administration Schedule; Drug Resistance, Neoplasm; Granulocyte Colony-Stimulating Factor; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Male; Methotrexate; Prostatic Neoplasms; Remission Induction

In order to establish a more effective and safer therapy for androgen-dependent prostate cancer, to be used in addition to hormonal therapy, the anti-tumor effects of intralesionally administered macrophages activated with recombinant interferon-gamma (INF-gamma), alone or in combination with recombinant interleukin-2 (IL-2) were studied in mouse prostate cancer models. Firstly, in terms of cellular adoptive immunotherapy, phagocytosis against Latex bead and cytotoxicity against Shionogi 115 cancer cell line (SC115) of macrophages activated with INF-gamma for 24 hour were investigated. One ml of 0.25% glycogen solution was intraperitoneally administered to male DS mice. Three days later, fluid was aspirated from the abdominal cavity and macrophages were separated for use in this experiment. Phagocytosis INF-gamma-dose-dependently increased and macrophages activated with 100 U/ml INF-gamma phagocytosed 78.3 +/- 4.5% (mean +/- SD) Latex bead. Cytotoxicity (modified MTT assay) of SC 115 by macrophages activated with 100 U/ml INF-gamma increased remarkably in comparison with non-activated macrophages and there was a significant increase in the effector-to-target-cell ratio to 40 in the activated group 77 +/- 4.3% (mean +/- SD) relative to 50 +/- 6.3% (mean +/- SD) in the non-activated group. Based on these in vitro findings, hormonal therapy and adoptive local immunotherapy, alone or together, were studied in mouse prostate cancer models. The prostate cancer model was prepared through the subcutaneous transplantation of SC115 in male DS mice and the treatments were initiated after tumors were palpable. The therapy protocols were as follows: Group I control and Group II received 20 mg/kg/day diethylstilbestrol diphosphate (DES-P) subcutaneously for 10 days, Group III received DES-P in combination with ten thousand units of IL-2 administered five times intralesionally, Group IV received DES-P in combination with 2 x 10(6) macrophages activated with 100 U/ml INF-gamma administered three times intralesionally, Group V received DES-P and IL-2 in combination with activated macrophages. The therapeutic efficiencies were evaluated by calculating the tumor volume and survival time. The results of the tumor volume on the 40th day post tumor transplantation were as follows (mean +/- SD): Group I 7,049 +/- 1,477 mm3, Group II 4,495 +/- 654 mm3, Group III 2,050 +/- 724 mm3, Group IV 2,782 +/- 970 mm3, Group V 1,555 +/- 514 mm3. The therapeutic groups showed significant tu

Topics: Animals; Antineoplastic Agents; Diethylstilbestrol; Immunotherapy; Injections, Intralesional; Interferon-gamma; Interleukin-2; Macrophage Activation; Macrophages; Male; Mice; Prostatic Neoplasms; Recombinant Proteins

To improve the therapeutic results as well as the patient's quality of life (QOL) in advanced prostatic carcinoma, total cystprostatectomy or pelvic exenteration was performed in combination with chemo-hormonal therapy before and after operation on twelve patients with stage D2 prostatic carcinoma who had infiltration in the periprostatic organs including urinary bladder and large intestine and showed strong bladder irritation, gross hematuria and ileus symptoms. Eight patients with severe cystic infiltration underwent total cystprostatectomy, urinary division and lymph node dissection, and four with ileus symptoms had pelvic exenteration, urinary division, proctostomy and lymph node dissection. As a rule of dosing schedule for chemo-hormonal therapy, 30-60mg/sq m of etoposide was continuously administered for 5 days before operation in addition to 250-500 mg of diethylbestrol diphosphate given for 30 days after operation. Furthermore, 2-3 courses of 30-60 mg/sq m of etoposide was administered for successive days, at 3-week intervals and then 30-60 mg/sq m of etoposide at 6-to-8-week intervals for 2 years together with 75-100 mg of chrolmadinone acetate as maintenance treatment. Nine of the 12 patients survived, including 4 patients with complete response, 3 patients with partial response and 2 patients with no change. These findings, suggested that the combination of surgical treatment and chemo-hormonal therapy is of use not only for providing an effective therapeutic means but also for improving the QOL in patients with advanced prostatic carcinoma.

Topics: Aged; Chemotherapy, Adjuvant; Cystectomy; Diethylstilbestrol; Drug Administration Schedule; Etoposide; Humans; Lymph Node Excision; Male; Middle Aged; Pelvic Exenteration; Prostatectomy; Prostatic Neoplasms; Urinary Diversion

From 1980 to 1991, 18 patients with pathologically proven stage D1 prostate cancer were treated with sequential hormone and radiation therapy at Cancer Institute Hospital. The patient mean age was 65.5 year old and mean follow-up period was 3.7 years. Diethylstilbestrol diphosphate or chlormadinone acetate was given prior to radiation therapy and 70 Gy of external radiotherapy using linear accelerator was sequentially delivered to the primary lesion in 35 fractions. Hormone therapy was continued following radiation therapy. Complete flattening of the primary lesion on digital examination was achieved in all cases. Complications of the treatment were minimal and transient. Tumor progression was observed in 4 cases and 2 of them died of cancer. Five-year non-progression rate, 5-year overall survival rate, 5-year disease specific survival rate and cancer death rate were 65%, 68%, 82% and 50% respectively. Prognoses of the patients with poorly differentiated cancer were worse than those with more differentiated cancer. Sequential hormone and radiation therapy for patients with stage D1 prostate cancer improved the patients' survival almost comparable to those of patients with stage C disease.

Topics: Adenocarcinoma; Aged; Chemotherapy, Adjuvant; Chlormadinone Acetate; Diethylstilbestrol; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Survival Rate

A case is reported about a 75-year-old man with a large abdominal lymph node metastasis caused by prostate cancer effectively treated by a high dose of diethylstilbestrol-diphosphate. The usefulness of diethylstilbestrol-diphosphate for prostate cancer patients with lymph node metastasis is emphasized.

Topics: Abdomen; Adenocarcinoma; Aged; Antineoplastic Agents; Diethylstilbestrol; Humans; Lymphatic Metastasis; Male; Prostatic Neoplasms

A new radioimmunoassay for determining diethylstilbestrol in serum using N-(4'-OH-[3'-125I]iodophenethyl)-6-(4-O-diethylstilbestryl)-hex anamide as a radiotracer and a double antibody as a separation reagent is described. The radiotracer is prepared by synthesizing 6-(4-O-diethylstilbestryl)-hexanoic acid and coupling its succinimidyl ester with mono-[125I]tyramine in tetrahydrofuran (16 h, 20-22 degrees C). The standard curve is linear (semi-log transformation) and the assay is sensitive (< 0.022 pmol/tube), reproducible (intra- and interassay coefficient of variation values, 5.3 and 8.1%, respectively), and accurate (recovery values, 95-101%), with a non-specific binding less than 3.2%. Diethylstilbestrol concentrations measured in sera of nine patients with prostatic cancer by the proposed assay ranged from 0.170 to 2.517 mumol/l, which corresponded to an only three-fold dosage variation. In all cases tested, dosing was adequate to retain markers of prostatic cancer in serum within accepted limits; nevertheless, individualization of dosing may be necessary to minimize toxicity.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Diethylstilbestrol; Ethanol; Female; Humans; Immunoglobulin G; Iodine Radioisotopes; Male; Middle Aged; Prostatic Neoplasms; Radioimmunoassay

A case of paraparesis due to thoracic vertebula metastasis of prostate cancer is reported. Treatment through a high dose of diethylstilbestrol diphosphate (DES-P) was very effective. Two and a half years later, the patient is ambulatory and relapse has not occurred. We recommend the use of a high dose of DES-P for spinal cord compression due to prostate cancer, instead of laminectomy or radiation.

Topics: Aged; Diethylstilbestrol; Humans; Male; Paralysis; Prostatic Neoplasms; Spinal Cord Compression; Spinal Neoplasms; Thoracic Vertebrae

Since the introduction of hormonal treatment for prostatic cancer by Huggins and Hodges in 1941, severe side effects of synthetic estrogen, which have overcome its benefit, have been reported in the U.S.A. and in European countries. However, in Japan the adverse effects of estrogen have been reported to be milder than in western countries, and estrogen still has an important role in the treatment of prostatic cancer in Japan. In this communication, the side-effects of synthetic estrogen administered to 109 prostatic cancer patients, who were admitted to Kyoto University Hospital between 1980-1990 are reported. Fifty-three (48.6%) of the 109 patients suffered adverse side effects of the estrogen, specifically cardiac disease (20.2%), fluid retention (14.7%) and hypertension (13.8%). Five of these patients died. Among the risk factors analyzed, daily dose, past history of cardio-vascular disease and ECG abnormalities were significantly correlated with the appearance of adverse effects. The reasons why the frequency of lethal side-effects is lower in our cases compared to findings reported by the Veterans Administration group may be the lower daily dose and cessation of estrogen administration when mild adverse effects appear and some other unknown factors, although the background of the patients and method of analysis are not comparable among them. The overall frequency of side-effects in prostatic cancer patients administered estrogen in our cases is not necessarily lower than in western countries, but the severity of the side effects was milder in our cases. We must be a ware of the potential adverse effects of estrogen.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Blood Pressure; Blood Urea Nitrogen; Body Weight; Diethylstilbestrol; Drug Administration Schedule; Electrocardiography; Estrogens; Heart; Hormones; Humans; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Risk Factors

Efficacy of orchiectomy and intravenous administration of diethylstilbestrol diphosphate (DESP) for the treatment of prostatic carcinoma was evaluated on 184 patients treated between 1975 to 1989. The patients were between 49 to 88 years old with a mean age of 73.4 +/- 8.3 years. Clinical stage was A in 9.8%, B in 12%, C in 26.6% and D in 51.6%. The histologically well, moderately and poorly differentiated adenocarcinoma were observed in 20.9, 29.4 and 49.7%, respectively. The 5-year survival rate of stage A, B, C and D calculated with the Kaplan-Meier method were 90, 49, 60 and 34%, respectively. The 5- and 10-year survival rate of the patients who had received orchiectomy was 53 and 24%, respectively, while that of the patients without orchiectomy was 38 and 14%, respectively. The 5 and 7-year survival rate of the patients treated with intravenous administration of DESP was 54 and 34%, respectively while that of the patients without DESP was 46 and 31%, respectively. These findings suggest that orchiectomy and intravenous administration of DESP in any form prolonged patient survival compared with only oral administration of estrogens or antiandrogens. Reactivation was seen in 24 (40%) of the 60 patients under sufficient observation. Clinical relapse occurred within an average of 32.3 +/- 26.4 months after primary hormonal manipulation. The average time to relapse in stage D was shorter than that in stage B and C. Reactivation was observed in the patients on interrupted treatment earlier than in the patients on continuous administration of drugs. Cardiovascular death followed by endocrine therapy was 7.4% in this study.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents; Chlormadinone Acetate; Combined Modality Therapy; Diethylstilbestrol; Drug Administration Schedule; Estramustine; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Survival Rate

The quality of life (QOL) was studied on 31 prostatic cancer (PC) patients, being followed at our out-patient-clinic during a relapse-free period. Fifteen of them were under treatment with a slow releasing LH-RH analogue (TAP-144 SR Depot) (TAP) and the other 16 prostatic cancer patients with synthetic estrogen (Honvan) (DES). The QOL of 37 benign prostatic hyperplasia (BPH) patients on conservative treatment was also studied. Concerning their general feeling of health, the prostatic cancer patients on TAP treatment felt subjectively better than those on DES. The social life of the patients on TAP or those who had BPH was less affected than that of those on DES. The quality of sexual life was worse for the prostatic cancer patients on both TAP and DES treatment than for the BPH patients.

Topics: Aged; Aged, 80 and over; Delayed-Action Preparations; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Sexual Behavior; Surveys and Questionnaires

A 71-year-old man visited our hospital complaining of a nodule in the left inguinal region. Pathological and immunohistochemical examination of the prostate and the mass and clinical examination revealed a case of prostatic cancer with lymph node metastasis, stage D. Chemoendocrine therapy (diethylstilbestrol diphosphate, cisplatin, adriamycin and carboquone) was performed and the patient responded well. This case indicated the presence of an unusual prostatic cancer in which large non-regional superficial lymph node metastasis occurred.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carbazilquinone; Cisplatin; Diethylstilbestrol; Doxorubicin; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Prostatic Neoplasms

The authors describe 2 cases of symptomatic spinal cord compression due to metastatic prostatic cancer. Both cases showed marked improvement of cord compression after hormone therapy, and decompressive laminectomy was not necessary. The management of prostatic cancer patients with symptomatic spinal cord compression is discussed.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Radiography; Spinal Cord Compression; Spinal Neoplasms; Thoracic Vertebrae

The patient presenting with severe bone pain after primary hormonal therapy, with vertebral collapse, or with uremia resulting from ureteric obstruction should be considered for intravenous stilbestrol diphosphate therapy. The urologist can expect early marked improvement in the patients' mobility and pain, with a reduction in analgesic requirements, from a single 7-day course of treatment. In addition, the drug is inexpensive and free of the side effects commonly associated with cytotoxic therapy. Accurate monitoring of the response is possible with serum prostate-specific antigen measurements, which also enable further therapy to be planned efficiently.

Topics: Diethylstilbestrol; Humans; Male; Pain; Prostatic Neoplasms

We reviewed retrospectively the medical records of 70 patients treated for prostate cancer who were followed for more than 10 years or until they died. All patients were treated by hormonal therapy and 54 of 70 patients (77 per cent) were combined with castration. Of 70 patients 10 (14.3 per cent) are alive now with an average follow up for 180.5 months. Of 60 patients with stage A and B only 3 died of the tumor. Of 56 patients with stage C and D, 10 and 18 patients died of the tumor, respectively. From the point of pathology, none of the patients with well differentiated adenocarcinoma died of the tumor. And in patients with stage A and B, pathologically well and moderately differentiated adenocarcinoma, there were no cancer death. On the other hand, a group of patients of poorly differentiated adenocarcinoma had a poor prognosis. In cases with well differentiated adenocarcinoma who discontinued hormonal medication (diethylstilbestrol diphosphate) no patients died of the tumor. From these observations we consider that, after long term hormonal medication, we can stop the hormonal medication for patients who have no positive prostate biopsy results for 4 years with well differentiated adenocarcinoma of stage A and B.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Diethylstilbestrol; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Retrospective Studies; Survival Rate

In previous work (P. Schulz et al., Cancer Res., 48: 2867-2870, 1988) we have demonstrated that diethylstilbestrol (DES), DES-monophosphate, and DES-diphosphate (DESDP) are generally cytotoxic at concentrations attained in patients' sera during therapeutic DESDP infusions for progressed carcinoma of the prostate. We have extended this work and addressed two questions: (a) Is DESDP itself a completely nontoxic prodrug which has to be transformed into the active species DES by a phosphatase? (b) Which metabolic or regulatory mechanism in a cell is the target of DES action? Using cell cultures in phosphatase-depleted media we could provide evidence that DESDP exerts cytotoxic activity only after conversion to DES. Oxygen electrode experiments and difference spectra with intact mitochondria demonstrated that DES did not act as an uncoupler, but inhibited electron flow from ubiquinone to cytochrome c1. Phenomena previously observed in DES-treated cells could be explained by distortion of the energy metabolism.

Topics: Acid Phosphatase; Animals; Antineoplastic Agents; Cattle; Cell Line; Cell Survival; Culture Media; Diethylstilbestrol; Electron Transport Complex III; Hot Temperature; Humans; Kinetics; Male; Mitochondria, Heart; Mitochondria, Liver; Oxygen Consumption; Prostatic Neoplasms; Rats; Tumor Cells, Cultured

For many years, diethylstilbestrol (DES) and its diphosphate (DESPP; Honvan) have been standard therapies for prostatic carcinoma. The effects of DES, its monophosphate (DESP) and of DESPP on the weights of accessory sex organs of mice and rats, and on the experimental Noble Nb-H and Nb-R prostatic carcinomas of the rat were, therefore, compared. In intact mature mice, all three compounds led to a strong and dose-dependent inhibition of seminal vesicle weights and testosterone levels, whereas only a slight antiandrogenic activity in castrated mice was found. In intact rats, DES, DESP and DESPP strongly inhibited accessory sex organ weights and testosterone levels. In castrated rats, however, no antiandrogenic activity was determinable. The prostate carcinoma-inhibiting effects of DES and DESPP were tested in comparison with castration in the transplantable hormone-sensitive Nb-H and Nb-R prostatic carcinoma in rats. Whereas castration caused only a retardation of tumor growth, DES and DESPP (3 x 0.1 mg/kg and 1.0 mg/kg weekly s.c.) led to an almost complete inhibition, which was significantly (P less than 0.01) better than the effect of castration. As the weights of accessory sex organs were identically reduced by either castration or the estrogens, a direct tumor-inhibiting effect of DES and DESPP in addition to their testosterone-lowering activity is obvious. This was proved in an experiment with castrated rats. The only slightly inhibitory activity of castration was strongly potentiated by concomitant administration of DES. Moreover, histological examinations revealed that Nb-H and Nb-R tumors were much more damaged by treatment with DES or DESPP than after castration. Morphometry of the tumors showed that tumor reduction is associated with a decrease in the ratio of the epithelial to the stromal density, i.e. there was an even more pronounced decrease in epithelial cells than that found by merely measuring tumor area. These studies show that the prostate carcinoma-inhibiting effect of DES and DESPP in the Nb model is superior to the effect of castration and that they act directly on the tumor cells used, even in castrated rats.

Topics: Androgen Antagonists; Animals; Carcinoma; Diethylstilbestrol; Genitalia, Male; Male; Organ Size; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Receptors, Androgen; Tamoxifen

The correlation between tumor volume of untreated tumor-bearing nude mice and serum concentration of prostatic acid phosphatase (PAP/RIA) was studied in the hormone-dependent serially transplantable human prostatic tumor models PC-82 and PC-EW. The normal serum level of PAP in control male nude mice without tumor was found to be 0.9 +/- 0.3 ng/ml. Elevated PAP serum concentrations were never found in animals without tumor (a highly specific diagnostic technique). A close correlation was observed between the concentration of PAP in the serum (range 0.3 to 154 ng/ml) and the tumor volume (range 10.0 to 6,530 mm3) of 104 untreated mice bearing a PC-82 or PC-EW human prostatic tumor. This correlation was comparable in both tumor lines (p less than 0.001). The positive effect of endocrine manipulation which resulted in tumor diameter decrease or growth arrest with regressive histological patterns, showed the normal PAP serum level, too. After successful treatment PAP was found to be normal, independent from the residual tumor mass. By contrast, in the event of only retarded tumor growth, the PAP level still correlated with the tumor burden.

Topics: Acid Phosphatase; Animals; Antineoplastic Agents; Cell Line; Diethylstilbestrol; Estrogen Antagonists; Humans; Indoles; Male; Mice; Mice, Nude; Neoplasm Transplantation; Orchiectomy; Prostatic Neoplasms; Tumor Cells, Cultured

In order to evaluate histological changes in cases of prostatic cancer following endocrine therapy, 25 extensive specimens were removed from prostates during periods of local control, and were examined with respect to prognosis. Shortly after the commencement of the endocrine therapy, there were noticeable degenerative changes in the cancer cells as well as structural changes such as desquamation of cells and loss of cancer nests. Later than two months from the start of therapy, stromal changes such as fibrosis and scar formation appeared. Coagulation necrosis of tumor tissue, inflammatory cell infiltration and granulomatous reactions were not as prominent. Within the first two months of treatment, the endocrine therapy uniformly affected the cancer tissues to some extent. After then, some showed relapsing viable cells in a part of the tumor, being judged to be no response. The others continued to respond to the therapy. The response was estimated as marked when such therapeutic changes appeared diffusely and profoundly over the tissues removed. Patients with a marked response had a good prognosis, indicating histological evaluation after endocrine therapy to provide a prognostic factor.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Cell Nucleus; Cytoplasm; Diethylstilbestrol; Ethinyl Estradiol; Fibrosis; Hexestrol; Humans; Male; Metaplasia; Middle Aged; Necrosis; Orchiectomy; Prognosis; Prostatic Neoplasms

The parenchymal damage of the liver after estrogen therapy for prostatic cancer, mainly treated with diethylstilbestrol diphosphate (DES-DP), was studied in the six autopsied cases, herein. The parenchymal disorder of the liver was "nonalcoholic steatohepatitis", reported by Ludwig et al., and its degree of disorder was dependent upon the administered dose of estrogen. The acceptable total dose of DES-DP was supposed to be about 150 g at maximum, according to the various degrees of damage examined histopathologically in the six cases who were administered at total doses of DES-DP from 12.6 g to 619 g. Comparison of the histopathologic damage to the liver function tests performed within 10 days before death revealed that only the serum levels of cholinesterase (ChE) were abnormally decreased, suggesting its importance to predict the degree of "nonalcoholic steatohepatitis" by monitoring of ChE.

Topics: Aged; Aged, 80 and over; Cholinesterases; Diethylstilbestrol; Fatty Liver; Humans; Male; Prostatic Neoplasms

We have examined the value of cholinesterase (ChE) that indicates the preservation ability of liver function, to assess the liver disorder owing to diethylstilbestrol diphosphate (DES-DP) administration in 25 prostatic cancer patients without castration. The correlation between ChE and the other factors such as age, total dose of DES-DP, duration of administration or ratio (total dose/duration), were studied by means of multiple regression analysis (MRA). In sixteen patients treated for less than 6 months, ChE was correlated with all factors by MRA with the coefficient of 0.645, and the coefficients of simple correlation between ChE and total dose and between ChE and administered duration, were -0.521 (p less than 0.05) and -0.596 (p less than 0.05), respectively. In nine patients treated for more than 6 months, ChE was correlated with all factors by MRA with the coefficient of 0.803, and the coefficient of simple correlation between ChE and ratio was -0.707 (p less than 0.05). According to these results and the permissible range of ChE, the total dose of administration for less than 6 months was estimated to be under 50 gram and its duration was within 100 days. The ratio in patients administered for more than 6 months was under 300 mg/day. Therefore, as far as the long-term hormonal treatment for prostatic cancer and preservation of liver function, we concluded that total dose of DES-DP should be less than 50 gram in less than 100 days for induction therapy and the daily dose of DES-DP should be less than 300 mg/day for maintenance therapy.

Topics: Age Factors; Aged; Aged, 80 and over; Cholinesterases; Diethylstilbestrol; Fatty Liver; Humans; Male; Middle Aged; Prostatic Neoplasms; Regression Analysis

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.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Cisplatin; Combined Modality Therapy; Diethylstilbestrol; Evaluation Studies as Topic; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Remission Induction

Topics: Administration, Oral; Animals; Antineoplastic Agents; Biotransformation; Diethylstilbestrol; Humans; Injections, Intravenous; Male; Prostatic Neoplasms; Rats

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diethylstilbestrol; Epirubicin; Humans; Ifosfamide; Male; Orchiectomy; Prostatic Neoplasms

Topics: Adenocarcinoma, Papillary; Diethylstilbestrol; Endometriosis; Humans; Male; Middle Aged; Prostatic Neoplasms

Androphilic protein in prostatic cancer was histochemically observed with dihydrotestosterone (DHT), R 1881, and mibolerone as ligands. Cancer cells were equally stained with fluorescent R 1881 and mibolerone, and this fluorescence seems to be made up of both the androgen receptor and progestin-binding protein. The staining with fluorescent DHT was weak. Sixty-two Stage D2 prostatic cancer patients were examined with histochemical androphilic protein, and they then received endocrine therapy. The presence of fluorescence of R 1881 was not correlated with grade, but a relationship between the presence of fluorescence and the response to endocrine therapy was noticed 6 months after the start of treatment. Moreover, fluorescence-positive patients showed better survival than fluorescence-negative patients. An examination with fluorescent DHT revealed a similar tendency to that of R 1881, but the frequency of positive fluorescence was lower, indicating that R 1881 is a suitable ligand in this type of study.

Topics: Androgen-Binding Protein; Biopsy, Needle; Combined Modality Therapy; Diethylstilbestrol; Ethinyl Estradiol; Fluorescence; Histocytochemistry; Humans; Ligands; Male; Neoplasm Proteins; Neoplasm Staging; Orchiectomy; Prostate; Prostatic Neoplasms; Protein Binding; Staining and Labeling

To evaluate a possible direct cytotoxic effect of diethylstilbestrol diphosphate (DESDP) in the treatment of prostate cancer we exposed three prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3), 2 nonprostatic neoplastic cell lines (KB and EJ), and one nontransformed cell line (MRC-5) to diethylstilbestrol (DES), diethylstilbestrol monophosphate, and DESDP at levels occurring in patients' sera during p.o. DES therapy (2 to 5 ng/ml) or DESDP infusions (1 to 20 micrograms/ml), respectively. With 5 ng/ml of DES no effect was seen in LNCaP cells, even after 14 days of exposure. In contrast, drug levels attained during DESDP infusions showed marked, dose-dependent cytotoxicity towards all cell lines under study. Prostatic cells were not exceptionally sensitive. High-dose DES slightly stimulated the synthesis of prostatic acid phosphatase in LNCaP cells. Formation of foci of polygonal cells was induced by 5 micrograms/ml of DES in cultures of MRC-5 fibroblasts. We conclude that, at high doses, DES liberated from DESDP acts upon a regulatory or metabolic mechanism common to many if not all human cells. Preferential sensitivity of prostate cancer cells in vivo may be due to high local phosphatase activity and/or DES accumulation in prostatic tissue.

Topics: Acid Phosphatase; Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Phosphoric Monoester Hydrolases; Prostate; Prostatic Neoplasms; Tumor Cells, Cultured

Controversy still exists as to whether oestrogens exert a direct effect on the prostatic cell. Incorporation of 75Selenomethionine (SeM) was used as a measure of protein synthesis by prostatic carcinoma cells in vitro to investigate the action of hormones on prostatic carcinoma cells in tissue culture. Stilboestrol (DES) and stilboestrol diphosphate (Honvan) inhibited protein synthesis in a proportion of patients, while testosterone was stimulatory. A similar effect was noted in cells from patients with benign hyperplasia (BPH). This work confirms that oestrogens have a direct inhibitory effect on prostatic cells at high concentrations which can be attained in patients given intravenous stilboestrol diphosphate.

Topics: Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estradiol; Humans; Male; Neoplasm Proteins; Prostatic Neoplasms; Selenomethionine; Testosterone; Tumor Cells, Cultured

Prostata cancer is one of the most dangerous tumours occurring in the older man. No general accepted therapy has existed up to now. In this study we were engaged on the pharmacokinetics of fosfestrol (Honvan) after oral administration. Its active principle is E-diethylstilbestrol (E-DES), the main metabolite. 250-1600 ng/ml E-DES are measurable after 60-110 min in the plasma of 11 patients suffering from metastatic prostata cancer who have been administered 360 mg fosfestrol orally. This range is equivalent to E-DES concentrations in plasma of 1-4 x 10(-6) mol/l. Thus that E-DES concentration range (5 x 10(-6) mol/l) is nearly attained for a short time to the concentration which hinders the mitosis of human breast cancer cells. Surprisingly similar but not higher concentration - time courses may be measured after a bolus infusion of 360 mg fosfestrol (lasting 45 min). Furthermore, E-DES-glucuronide, E-DES-sulphate and the mixed E-DES-glucuronide-sulphate could be observed in plasma after oral administration. In spite of the high sensitivity of the analytical method (limit of detection for fosfestrol 0.1 micrograms/ml and for E-DES and its mono-conjugates 2-5 ng/ml) neither fosfestrol nor E-DES-monophosphate are detectable in plasma due to the biotransformation of fosfestrol, which is already metabolized by the enzymes of the gut wall. Both phosphates only exist in plasma after intravenous infusion. Further investigations are linked with the question if phase II-conjugates of E-DES can eventually be prodrugs delivering E-DES by cleavage of the ester bonds.

Topics: Administration, Oral; Aged; Androgen Antagonists; Antineoplastic Agents; Biological Availability; Biotransformation; Carcinoma; Chemical Phenomena; Chemistry; Diethylstilbestrol; Estramustine; Estrogens; Humans; Ketoconazole; Male; Middle Aged; Neoplasm Metastasis; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms; Protein Binding

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Diethylstilbestrol; Doxorubicin; Drug Therapy, Combination; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Diethylstilbestrol; Dihydrotestosterone; Humans; Male; Medroxyprogesterone; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms

Topics: Antineoplastic Agents; Bone Neoplasms; Cyclophosphamide; Diethylstilbestrol; Drug Combinations; Humans; Male; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Medronate

Estramustine-binding protein (EMBP) in human prostatic cancer before and after androgen-deprivation therapy was determined with an immunohistochemical technique. Although a rabbit polyclonal antiserum raised against rat EMBP was used, all the prostatic tumours displayed positive staining for EMBP. Staining was found exclusively in the cytoplasm of the epithelium, whereas nuclei, fibromuscular stroma and, in general, also lumina were negative. The staining intensity was higher in moderately and poorly differentiated, than in well differentiated tumours. EMBP immunostaining intensity decreased markedly from pretreatment levels in patients with remission, but returned to these levels when relapse occurred despite androgen withdrawal. Altered EMBP staining intensity was evident as early as 10 days after start of therapy in responding patients. EMBP may therefore be a marker of therapeutic response in human prostatic cancer. Provided that immunohistochemical measurements can be performed on fine-needle aspirates, EMBP analysis may be a direct and early means for predictive distinction between responding and non-responding patients.

Topics: Animals; Antineoplastic Agents; Carrier Proteins; Diethylstilbestrol; Estradiol; Estradiol Congeners; Humans; Immunoenzyme Techniques; Male; Orchiectomy; Prostate; Prostatic Neoplasms; Prostatic Secretory Proteins; Rats

The testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin levels were measured by radioimmunoassay up to one year in 21 patients with prostatic carcinoma treated with diethylstilbestrol diphosphate (DESP), 50 mg/day, and chlormadinone acetate (CMA), 100 mg/day. The purpose of this treatment was to reduce the cardiovascular side effects which were believed to occur dose-dependently and to achieve the direct drug action to the prostate gland. The same measurements were made on 9 patients treated with DESP, 50 mg/day, alone. Marked reduction of plasma testosterone and FSH levels with weaker LH suppressions was observed during the first 1-3 months in both groups. The same levels were maintained up to the end of follow-up in DESP and CMA treatment group. In the DESP treatment group, the plasma level of testosterone showed a gradual increase to 1.0 +/- 0.5 ng/ml at the sixth month. Prolactin level increased gradually in both groups. Cardiovascular side-effects were found in 29% of the patients treated with DESP and CMA and in 22% of those treated with DESP alone. In two patients in the former group gynecomastia with lactation was observed.

Topics: Aged; Aged, 80 and over; Chlormadinone Acetate; Diethylstilbestrol; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Prolactin; Prostatic Neoplasms; Testosterone

Following the intravenous drip infusion of diethylstilbestrol diphosphate (DES-DP), the diethylstilbestrol (DES) concentrations both in plasma and prostatic tissue obtained from patients with prostatic carcinoma were measured by radioimmunoassay and the effects of DES on the activity of 5 alpha-reductase in the prostate obtained from BPH patients were determined in vitro. Further, the changes in the activity of 5 alpha-reductase in the prostate from the BPH patients who received DES-DP infusion were also determined. The plasma and prostatic tissue concentrations of DES rapidly declined from 2.3 micrograms/ml and 1.6 micrograms/g wet weight 1 h after DES-DP infusion to 0.8 microgram/ml and 0.25 microgram/g wet weight 3 h after DES-DP infusion, respectively, and decreased gradually thereafter until 24 h. In in vitro study progressed by BPH specimens, the 5 alpha-reduction rate was completely inhibited by an addition of 5 x 10(-4) M of DES and the DES concentration on the inhibition rate of 50% was 4 x 10(-5) M. In in vivo study, the mean production rate of 5 alpha-dihydrotestosterone (DHT) in the control specimens of BPH without infusion of DES-DP was 14.0 +/- 3.4 nmol/15 min/mg protein and the production rate of DHT in the DES-DP infused specimens of BPH was 14.7 nmol/15 min/mg protein at 3 h and 15.2 nmol/15 min/mg protein at 12 h after the termination of DES-DP infusion. These results indicated that intravenously administered DES-DP did not act via the inhibition of 5 alpha-reductase in the prostatic cells for producing the clinical effects.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Diethylstilbestrol; Dihydrotestosterone; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Time Factors

Topics: Aged; Androgens; Chorionic Gonadotropin; Cyclic AMP; Diethylstilbestrol; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testis

Effects of estrogen treatment on testicular human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) receptors in man were investigated. Ten patients (aged 58 to 75, mean 67 years) with prostatic cancer were treated with diethylstilbestrol diphosphate (DESDP) (300 mg daily, oral administration). They were divided into two groups: 5 of them (aged 58 to 74, mean 67 years) were orchiectomized after 7 days of treatment and the remainder (aged 60-75, mean 67 years) after 6 months of treatment. hCG and FSH receptors in the resected testes of each group were measured and compared with those of age-matched prostatic cancer patients without any treatment (controls). After 7 days and 6 months of DESDP treatment, the number of hCG receptors decreased to approximately 53% and 24%, respectively, of that of the controls. FSH receptors in the testes of the patients treated with DESDP did not differ significantly from those of the controls.

Topics: Aged; Chorionic Gonadotropin; Diethylstilbestrol; Follicle Stimulating Hormone; Humans; Male; Middle Aged; Prostatic Neoplasms; Receptors, FSH; Receptors, LH; Testis

Topics: Antineoplastic Agents; Diethylstilbestrol; Humans; Interferon Type I; Killer Cells, Natural; Male; Prostatic Neoplasms

A five-year follow-up is presented of 123 patients with recently diagnosed prostatic cancer, confirmed histopathologically and treated with fosfestrol and bromocriptine. The combined treatment has been shown to prevent most of the complications and side effects of therapy, thus it is considered to be worthy of recommendation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bromocriptine; Diethylstilbestrol; Follow-Up Studies; Humans; Male; Prostatic Neoplasms

The behaviour of the transaminases under contra-sexual initial treatment of the carcinoma of the prostate gland with Cytonal in contrast to Turisteron was compared. In these cases under the Cytonal therapy as an expression of the hepatotoxic side effects a double as high serum activity of the transaminase ALAT could be proved compared with the serum activity of the patients treated with Turisteron. Due to the good tolerability and the only insignificant hepatotoxic reactions Turisteron is well suited for the long-term treatment of the carcinoma of the prostate gland.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Diethylstilbestrol; Ethinyl Estradiol; Humans; Liver Function Tests; Male; Middle Aged; Prostatic Neoplasms

Apart from their antigonadotropic effect oestrogens also directly inhibit the androgen secretion of the testicles. Thus, on the 20th day of treatment the LH-level after 12 g diethylstilbestrol diphosphate (DSDP) decreases only to approximately 50% of the initial value, while the whole testosterone (T), however, is reduced to less than 5%. The sexual hormone binding globulin is significantly more increased (p less than 0.001) by the estrogen treatment than after orchidectomy only. Therefore, the free, biologically active T-level in the plasma consists of more than one third of the level after exclusive orchidectomy. The treatment with the depot estrogen Turisteron is clarly superior to the usual treatment Oestrasid implants. Both with and without orchidectomy the free testosterone level is significantly lower than after Oestrasid implants plus orchidectomy. Therefore, this therapy can successfully be used in the treatment of the carcinoma of the prostate also without orchidectomy.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents; Combined Modality Therapy; Delayed-Action Preparations; Diethylstilbestrol; Ethinyl Estradiol; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Testosterone

A 65-year-old man was hospitalized with bloody sputum. His chest X-ray showed multiple nodules in both lung fields. Transbronchial lung biopsy demonstrated a poorly differentiated adenocarcinoma, which suggested that respiratory abnormalities might be metastatic cancer. Because he had noticed pollakisuria and dysuria, urologic consultation was sought. The findings of digital examination, urethrography, and ultrasonotomography suggested that he had an advanced prostate cancer. In addition, tumor markers of prostatic acid phosphatase (PAP), acid phosphatase (ACP), and prostate antigen (PA) showed abnormal titers; 120 ng/dl, 166 IU/l, and 15.4 ng/ml, respectively. The prostate tissue obtained by transperineal biopsy revealed histopathologically adenocarcinoma and positive findings in immunohistochemical staining for PAP and PA as well as the specimens from the lung. Bilateral orchiectomy and medication of 250 mg of DESD daily as an antiandrogen therapy improved respiratory symptoms. One week after the operation, the multiple shadows on the chest X-ray diminished dramatically. Moreover, serum values of PAP and PA also decreased to the normal range. He is alive in a stable condition 6 months after the operation.

Topics: Adenocarcinoma; Aged; Combined Modality Therapy; Diethylstilbestrol; Humans; Lung Neoplasms; Male; Prostatectomy; Prostatic Neoplasms

Clinical trials have utilized intermittent diethylstilbestrol diphosphate (DES) therapy in advanced symptomatic prostatic carcinoma to diminish the morbidity of standard endocrine therapy. To determine the effect of intermittent DES administration on the Dunning R3327 rat prostatic adenocarcinoma 60 days following tumor implant, 6 groups were randomly assigned: control (N = 8), castrate (N = 10), high dose DES (N = 8, 1.6 micrograms/ml DES continuously in drinking water), low dose DES (N = 10, 0.4 microgram/ml continuously in drinking water), intermittent high dose DES (N = 10, 1.6 micrograms/ml DES in drinking water for 1 week, then off for 3 weeks), and intermittent low dose DES (N = 10, 0.4 microgram/ml DES for 1 week, then off for 3 weeks). Results indicate that low or high dose DES, and intermittent low or intermittent high dose DES during the week of administration were able to reduce serum testosterone to castrate levels (0.1 ng/ml). After withdrawal of intermittent DES, serum testosterone returned toward control levels (1.0 ng/ml). Initial mean tumor burden between control and treatment groups was not significantly different. All DES exposed rats had a tumor volume at death (range, 15.6-18.3 cm3) smaller than control (mean, 25.4 cm3) or castrate (mean, 40.8 cm3) rats. Despite this significant survival advantage from the time of randomization was achieved only in castrate (median survival, 331 days) or high dose DES (median survival, 359 days) groups compared to control (median survival, 225 days). Similarly, significant prolongation in tumor doubling time was achieved only by rats receiving castration or high dose DES. Intermittent DES administration controls tumor volume but does not provide a survival advantage. In this respect, intermittent DES is inferior to castration.

Topics: Animals; Antineoplastic Agents; Body Weight; Diethylstilbestrol; Drug Administration Schedule; Male; Orchiectomy; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone

Topics: Antineoplastic Agents; Biological Availability; Biotransformation; Diethylstilbestrol; Humans; Kinetics; Male; Prostate; Prostatic Neoplasms; Radioimmunoassay

Topics: Antineoplastic Agents; Diethylstilbestrol; Estrogens; Humans; Male; Prognosis; Prostatic Neoplasms; Receptors, Androgen

Two patients, aged 72 and 65 years, each underwent two prostatic resections spaced four and two years apart, respectively. In both cases the earlier procedure showed widespread adenocarcinoma with only occasional endocrine cells, while tissue from the later operations showed prostatic carcinoids. It is suggested that the conventional adenocarcinomas were sensitive to hormonal manipulations used in treatment, but that the originally sparse carcinoid components were resistant to this form of treatment and hence became the predominant tumours. These findings imply that endocrine differentiation in prostatic carcinoma leads to lack of sex steroid sensitivity.

Topics: Adenocarcinoma; Aged; Carcinoma; Cell Transformation, Neoplastic; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

After the identification of E-diethylstilbestrol (DES)-glucuronide-sulphate-bis-conjugate in the plasma of patients suffering from metastatic prostatic cancer for the first time we have registered the plasma concentration-time curves of fosfestrol (Honvan) and its monophosphate as well as E-DES and its 3 conjugates over 8 h with a further 10 patients. Maximum concentrations fluctuate between 1 and 32 micrograms/ml plasma. Therefore the greatest amount of E-DES formed by hydrolysis and its conjugates are hidden in deeper compartments, probably in the lung. The oxidative metabolism of E-DES compared with its conjugation reactions is less important. Only E-DES monoglucuronide and small amounts of E-DES-glucuronide-sulphate-bis-conjugate are detectable in urine. Renal excretion of those metabolites which are in the enterohepatic circle in form of E-DES-glucuronide and E-DES-glucuronide-sulphate-bis-conjugate could be observed even over a period of 72 h.

Topics: Aged; Antineoplastic Agents; Diethylstilbestrol; Humans; Infusions, Intravenous; Injections, Intravenous; Kinetics; Male; Middle Aged; Prostatic Neoplasms

Chemilumenescence (CL) occurs due to the phagocytosis of bacteria and of tumor cells by polymorphonuclear neutrophils (PMN). Levels of CL were measured in patients with prostatic cancer and from normal subjects. Patients with advanced disease (stage C, D) showed no elevated CL levels as compared to healthy individuals or patients with minimal disease (stage A, B). Following external radiation therapy in patients with stage A-C prostatic carcinoma high levels of CL were recorded. Estrogen medication also resulted in increased CL levels, while estramustine did not affect phagocytic activity. Intradermal BCG vaccination caused increased PMN activity. Progressive prostatic cancer in hormone treated patients was associated with increased CL as compared to patients with stable or regressive disease.

Topics: Antineoplastic Agents; BCG Vaccine; Diethylstilbestrol; Estramustine; Granulocytes; Humans; Luminescent Measurements; Male; Phagocytosis; Prostatic Neoplasms

High affinity binding of the synthetic steroids methyltrienolone (R1881) and promegestone (R5020) to cytosol protein from the Dunning (R3327) experimental prostatic carcinoma of the rat was investigated. Animals bearing tumours of approx 1.5 cm mean diameter were either left untreated, or were administered diethylstilbestrol diphosphate (DESP) in the drinking water in doses close to those used clinically for the treatment of human prostatic carcinoma. Tumours were excised after 10-40 days, and binding of [3H]R1881 and [3H]R5020 to tumour cytosol was characterized using Scatchard analysis, sucrose density gradient centrifugation, and steroid competition, under conditions optimal for the conservation and assay of progesterone receptor. Both ligands were bound in much higher concentrations by cytosol from DESP-treated tumours than from untreated tumours. Binding was of high affinity (Kd congruent to 1 nM), was specific for progestins, and sedimented in peaks at approximately 8S and approximately 4S in sucrose density gradients. We conclude the DESP treatment of rats bearing the R3327 prostatic carcinoma induces synthesis of progesterone receptor in this tumour.

Topics: Adenocarcinoma; Animals; Binding, Competitive; Centrifugation, Density Gradient; Cytosol; Diethylstilbestrol; Estrenes; Male; Metribolone; Norpregnadienes; Promegestone; Prostatic Neoplasms; Rats; Receptors, Progesterone

Four hundred mg of UFT and 100 mg of cyclophosphamide were orally administered to patients with prostate cancer, additional to conventional hormone therapy. Four cases are presented here, all of whom showed good response to the therapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms; Tegafur; Uracil

Nine men with histologically confirmed stage D cancer of the prostate were evaluated with serial serum testosterone levels after being treated with bilateral orchiectomy or intravenous estrogen. Bilateral orchiectomy produced castrate serum testosterone levels (less than or equal to 50 ng. per 100 ml.) within 2 to 6 hours (mean 3 hours) after surgery. Intravenous estrogen therapy did not consistently produce castrate serum testosterone levels immediately but did significantly decrease testosterone within 12 hours after infusion. Both forms of therapy are safe, produce a clinically effective response and offer advantages for patients with advanced prostatic cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Castration; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Testosterone; Time Factors

A clinical study of the adverse effects induced by the endocrine therapy with a high dose of estrogen in 45 patients with stage C or D prostatic carcinoma is conducted. Transient decreases of hemoglobin and serum protein values were observed after administration of estrogen. The levels of glutamine-oxaloacetic and glutamic-pyruvic transaminase showed a transient increase. The value of serum total cholesterol and electrolytes showed no changes. Serial evaluations of electrocardiograms have played a minor role in the observation of cardiovascular disease. Up to date we have not experienced cardiovascular death in our cases during the endocrine therapy.

Topics: Aged; Antineoplastic Agents; Castration; Cholesterol; Combined Modality Therapy; Diethylstilbestrol; Dose-Response Relationship, Drug; Edema; Electrocardiography; Electrolytes; Hemoglobinometry; Humans; Injections, Intravenous; Intracranial Embolism and Thrombosis; Male; Middle Aged; Prostatic Neoplasms

Twenty-five patients with metastatic prostate cancer resistant to primary hormone therapy, received high-dose intravenous diethylstilbestrol diphosphate (Stilphostrol [Miles Pharm], DES-P) in a Phase II study using established response criteria. Objective response rate was 17%, while 22% of the patients were subjectively improved. Moderate gastrointestinal toxicity was reported in 10 patients (40%). Thromboembolic complications were seen in 2 (8%). The role of high-dose Stilphostrol in the treatment of hormone-resistant prostate cancer is limited.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antineoplastic Agents; Bone Neoplasms; Castration; Combined Modality Therapy; Diethylstilbestrol; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms

A method for the radioimmunoassay of diethylstilbestrol (DES) was established and it was used to measure the plasma concentration of DES in patients with prostatic carcinoma receiving intravenous drip infusion of 500 mg of diethylstilbestrol diphosphate (DES-DP). The sensitivity of this assay system was 40 pg per tube, with a recovery of 98%. The cross reactivity of the anti-DES antibody with estradiol, testosterone, and ethynylestradiol was less than 0.01% of DES, and that with DES-DP was 0.7%. In patients with prostatic carcinoma, plasma DES concentration at 6 and 24 hr after was declined to 10.2% and 4.4% of the level at the termination of intravenous administration of DES-DP, respectively; however, the concentration in patients with renal dysfunction was higher than that in ones with normal renal function.

Topics: Diethylstilbestrol; Humans; Kinetics; Male; Prostatic Neoplasms; Radioimmunoassay

Hypophosphatemia and osteomalacia have been described in patients with metastatic prostate cancer. The mechanism of hypophosphatemia in prostate cancer is not known. A decrease in serum phosphate levels was observed in 16 of 18 patients with metastatic prostate cancer treated with high-dose diethylstilbestrol diphosphate. To determine if the fall in serum phosphate was indeed due to diethylstilbestrol diphosphate, the data from several similar groups of patients treated with chemotherapy and combined chemohormonal therapy that included diethylstilbestrol diphosphate were re-examined. Fifty-eight patients were treated with doxorubicin, doxorubicin plus cis-platinum, doxorubicin plus diethylstilbestrol diphosphate, or diethylstilbestrol diphosphate alone. A significant decrease in serum phosphate levels was seen only in patients treated with diethylstilbestrol diphosphate. Hypophosphatemia and possibly osteomalacia in metastatic prostate cancer may be related to estrogen therapy.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diethylstilbestrol; Doxorubicin; Humans; Male; Middle Aged; Phosphates; Prostatic Neoplasms

A 67-year-old patient with stage C giant prostate cancer was treated with a combination of endocrine administration and chemotherapy. After administration of diethylstilbestrol diphosphate (250 mg/D, 16 days), bilateral orchiectomy and subsequent CDDP administration (30 mg/D X 5 days, e. 3 weeks, 4 courses), the primary tumor was reduced by about 90%. Clinical response was evaluated as partial response. Serum acid phosphatase activity, prostatic acid phosphatase, prostate antigen and nuclear DNA histogram served as useful tumor markers and changed in parallel to clinical course.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents; Castration; Cisplatin; Combined Modality Therapy; Diethylstilbestrol; Drug Therapy, Combination; Humans; Male; Prostatic Neoplasms

A homogeneous ion pair extraction technique enables the nearly quantitative isolation of fosfestrol (1) (Honvan) and up till now of three of its metabolites from the plasma of patients suffering from metastatic prostata cancer. The detection occurs by HPLC with UV-detector. The range of detection is in the lower microgram range. It is the first time that plasma levels of 1 and its monophosphate (2) can be measured.

Topics: Aged; Antineoplastic Agents; Chromatography, High Pressure Liquid; Diethylstilbestrol; Humans; Injections, Intravenous; Male; Neoplasm Metastasis; Prostatic Neoplasms; Stereoisomerism

Combined chemohormonal therapy of metastatic prostate cancer has not been previously evaluated in patients failing primary hormones (estrogens and/or orchiectomy). The combination of Adriamycin and high-dose diethylstilbestrol diphosphate (Stilphostrol) was studied in 19 heavily pretreated patients, to document toxicity and patient acceptability. Major toxicity was myelosuppression, cardiac failure and venous thrombosis. Clinical improvement was noted in 10/16 (63%) of evaluable patients. Patients with pre-existing cardiac disease or venous thrombosis are not suitable for this therapy.

Topics: Aged; Diethylstilbestrol; Doxorubicin; Drug Therapy, Combination; Heart Arrest; Humans; Leukocyte Count; Male; Middle Aged; Neoplasm Metastasis; Pilot Projects; Prognosis; Prostatic Neoplasms; Thrombophlebitis

The effects of in vivo diethylstilbosterol phosphate (DES-P) on lymphoid cells were studied in six patients with adenocarcinoma of the prostate. The administration of 500 mg DES-P intravenously caused increased numbers of circulating granulocytes, monocytes, and non-T lymphocytes lasting for 24-48 hours. The natural killer activity, as measured in a three-hours 51Cr-release assay with K562 cells as targets, was transiently depressed four hours after drug injection. Parallel variations were found in the fraction of lymphocytes bearing receptors for the Fc part of IgG. In mixed lymphocyte culture (MLC) the responding capacity of the T cells and the stimulatory capacity of the non-T cells were unaffected. In vitro preincubation with DES-P overnight was not toxic to the lymphocytes. To be suppressive in MLC DES-P had to be added in concentrations one thousand times higher than those of hydrocortisone. It is concluded that a single dose of DES-P in vivo modulates the kinetics of recirculating lymphoid cells.

Topics: Aged; Cytotoxicity, Immunologic; Diethylstilbestrol; Humans; Immunosuppressive Agents; Killer Cells, Natural; Leukocyte Count; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Middle Aged; Prostatic Neoplasms; T-Lymphocytes

In 45 patients with newly diagnosed carcinoma of the prostate, 1509 radioimmunological assays (RIA) were done for serum testosterone (T), prolactin (PRL) and growth hormone (GH). The patients were divided into 4 groups and treated with gradually lowered doses of Fostrolin and bromocriptin. It was noted that after high doses of Fostrolin, T levels did not markedly decrease, and PRL concentrations increased manifold. Small doses of Fostrolin, however, caused a drop in T and PRL levels. In the light of the results of up-to-date investigations and of the role played by PRL in a higher incidence of prostatic tumours, employment of bromocriptin, a prolactin antagonist, in the treatment of prostatic cancer seems to be justified. Reduction of T concentration below castration level and attainment of trace PRL levels in response to small doses of Fostrolin and bromocriptin had a favourable effect on the clinical course of the malignant disease.

Topics: Antineoplastic Agents; Bromocriptine; Diethylstilbestrol; Drug Therapy, Combination; Humans; Male; Prolactin; Prostatic Neoplasms; Testosterone

The levels of plasma testosterone, testosterone-oestradiol binding globulin (TeBG) and total serum acid phosphatase (TSAP) following antiandrogenic hormone therapy were investigated in 17 patients with prostatic carcinoma. The low levels of plasma total and free testosterone induced by castration decreased further after diethylstilboestrol diphosphate (DES-D) administration. Plasma TeBG binding capacity after castration was 118.9% of the pre-treatment level and increased to 193.9%, 204.0% and 212.7% at 1, 2 and 3 weeks after DES-D dosing. The in vitro binding of 3H-testosterone to TeBG was not influenced in the presence of DES-D or stilboestrol. Clinical response following the DES-D therapy was associated with a decrease in the levels of TSAP. A significantly inversed correlation was found between the decrease in TSAP and increase in TeBG at completion of DES-D therapy. These results suggest that the high binding capacity of TeBG lowers the biologically active fraction of testosterone and thus may produce clinical effects.

Topics: Acid Phosphatase; Castration; Diethylstilbestrol; Electrophoresis, Polyacrylamide Gel; Humans; Male; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Testosterone

Since 1972 in the Urology Department at Darmstadt Hospital the Honvan-high-dose-therapy of 130 patients with metastatic prostatic carcinoma has been carried out under standardizing condition. The analysis shows that there is no significant difference between the patients with prophylaxis against thrombosis (Macrodex and Dihydergot-Heparin) and without prophylaxis. The patients with anti-thrombotic prophylaxis demonstrated significantly higher incidence of reversible elevation of transaminases. The effect of Heparin is probably responsible for this.

Topics: Aged; Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Retrospective Studies; Thromboembolism

Topics: Adenocarcinoma; Aged; Diethylstilbestrol; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Pulmonary Embolism

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Diethylstilbestrol; Disseminated Intravascular Coagulation; Humans; Injections, Intravenous; Male; Prostatic Neoplasms

Thirty-six patients with prostatic carcinoma and benign prostatic hyperplasia (BPH) were studied. Transurethral resection (TUR) was performed in all, and serum and tissue ribonuclease (RNase) levels were determined with the spectrophotometric method using yeast RNA as the substrate. In patients with untreated prostatic carcinoma, statistically significant increased RNase levels were found in serum and tissue. Treatment with diethylstilbestrol diphosphate (DESDP) led to a decrease in RNase levels. In the same patients RNase serum levels after DESDP treatments also showed a parallel decrease with serum prostatic acid phosphatase (sPAP) levels. We have concluded that the serum RNase measurement may be useful for TNM classification and immunostaging.

Topics: Acid Phosphatase; Diethylstilbestrol; Humans; Hyperplasia; Male; Probability; Prostate; Prostatic Neoplasms; Ribonucleases

The kinetic behavior of diethylstilbestrol (DES) produced from stilphostrol has been studied in man, dog and rat. A sensitive and selective assay for DES in plasma and tissues has been developed with the use of gas chromatographic separation and mass spectrometric detection. In patients with prostate cancer, the plasma concentrations of DES produced by 1,000-mg. infusions of stilphostrol are 1,500 times the DES concentrations produced by conventional oral DES doses. The pharmacokinetics of DES show 2 separate phases; 1 with a t1/2 of approximately 1 hour, another with a t1/2 of approximately a day. In rats, stilphostrol does not selectively liberate DES in the prostate compared to dosing with DES itself. In dogs, a 50-mg. tablet of stilphostrol was bioequivalent to 40 mg. of DES taken orally. Some of these data support the idea that the high DES concentrations produced by stilphostrol infusions underlie in its ability to produce objective responses in patients refractory to conventional oral DES therapy.

Topics: Animals; Antineoplastic Agents; Biological Availability; Diethylstilbestrol; Dogs; Humans; Kinetics; Male; Prostatic Neoplasms; Rats; Rats, Inbred Strains

Topics: Adult; Aged; Androgens; Antineoplastic Agents; Diethylstilbestrol; Estradiol; Estradiol Congeners; Humans; Male; Middle Aged; Organophosphorus Compounds; Pregnenolone; Progesterone; Prostatic Neoplasms; Steroids; Sulfuric Acids; Testis

Topics: Aged; Diethylstilbestrol; Estradiol; Humans; Male; Middle Aged; Organophosphorus Compounds; Prostatic Neoplasms; Testosterone

In vitro pretreatment of peripheral blood leukocytes (PBL) from patients with prostatic cancer with therapeutically significant levels of diethylstilbestrol diphosphate (DES-P) has been shown to suppress cell-mediated tumor-associated immunity (TAI). In the present retrospective evaluation of TAI in 27 patients with prostatic cancer, prior to and following the receipt of nonhormonal and hormonal, ie, estrogen and/or orchiectomy, therapy, patients receiving hormonal therapy possessed significantly (p less than 0.05) lower levels of TAI, irrespective of the in vitro pretreatment of their PBL with DES-P. Suppression of TAI by in vitro pretreatment of PBL with DES-P and in prostatic cancer patients receiving estrogen therapy parallels and extends earlier observations of the estrogenic suppression of nonspecific, mitogen-induced cellular responsiveness. The clinical relevance of the immunosuppressive effects of hormonal therapy on tumor-host responsiveness is considered in view of the present and previous studies.

Topics: Adenocarcinoma; Castration; Diethylstilbestrol; Humans; Immunity, Cellular; Immunosuppression Therapy; In Vitro Techniques; Male; Prostatic Neoplasms

23 patients with prostatic cancer were treated with (Estracyt) estramustine phosphate disodium, (Hexron) hexestrol, and (Honvah) diethylstilbestrol 4, 4-diphosphoric ester. 16 cases were given 560-840 mg of Estracyt, 6 cases 30 mg of Hexron, and 1 case 200 mg of Honvan orally daily. Fasting serum lipids and lipoproteins fractions were measured before and during this treatment with these drugs. The results were as follows. 1) In the 1-2 months of Estracyt administration a decrease of (TC) total cholesterol and extreme increase of (TG) triglycerides were confirmed. 2) In those 5 cases where 840 mg of Estracyt/day was given, almost no difference was observed in their TC, (NEFA) free fatty acids, or (PL) phospholipid values. 3) Cardiovascular complications although not serious, were found in 2 cases of the group receiving Estracyt. With these 2 cases, their beta+pre-beta/alpha lipoprotein fraction ratio decline was either very gradual or rather turned to increase markedly despite the extreme rise of their TG values. 4) The serum lipid values in the group receiving Hexron did not show any obvious changes in TG. These values did not change much in the first 5-6 months but an increase was seen between 7-9 months. Lipoprotein fractions were similar to those in the Estracyt group. 5) With those receiving Honvan, TG values began to rise 2-4 weeks following administration. In view of the above results, the coronary risk factors which are a consequence of Estracyt, Honvan, or Hexron ingestion for treatment of prostatic cancer must be taken very seriously and must be closely monitored. (Authors' modified)

Topics: Aged; Diethylstilbestrol; Estramustine; Hexestrol; Humans; Lipids; Lipoproteins; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Hyperplasia; Prostatic Neoplasms

With the help of the lysis time method after Blix as well as of the radial immune diffusion after Mancini in blood donors and in patients with histologically ascertained carcinoma of the prostate estimations of plasminogen were performed. In the group of patients the controls were repeated after having finished the initial therapy. While with the help of the two methods plasminogen values were established before therapy which essentially were within the normal, after the initial therapy with cytonal a significant increase of plasminogen developed. The importance of these findings is discussed in connection with a possible increased rate of fibrinolysis in carcinoma of the prostate.

Topics: Aged; Diethylstilbestrol; Enzyme Activation; Fibrinolysin; Fibrinolysis; Humans; Male; Middle Aged; Plasminogen; Prostatic Neoplasms

Transient thrombocytopenia was noted to occur in ten of 13 patients with advanced carcinoma of the prostate undergoing intravenous diethylstilbestrol diphosphate therapy. This was not associated with abnormalities of the initial platelet count or other parameters of the hemogram. There was no evidence of disseminated intravascular coagulation in these patients. No serious bleeding episodes occurred secondary to the thrombocytopenia. Following diethylstilbestrol diphosphate infusion, platelet counts generally returned to pretreatment levels. While the mechanism of action of the thrombocytopenia is unclear, we hypothesize a transient bone marrow toxicity as the cause of this phenomenon.

Topics: Adenocarcinoma; Bone Marrow; Diethylstilbestrol; Humans; Male; Platelet Aggregation; Platelet Count; Prostatic Neoplasms; Thrombocytopenia

Diethylstilbestrol diphosphate (DES-P) has shown effective symptomatic relief in patients with metastatic carcinoma of the prostate. Although there is little known about its role in soft tissue metastasis, our experience in 3 patients with advanced carcinoma of the prostate infiltrating the trigone and ureterovesical junction revealed significant improvement of hydronephrosis. All patients failed to respond to conventional doses of stilbestrol. Diethylstilbestrol diphosphate is recommended in the treatment of advanced carcinoma of the prostate with soft tissue metastasis. It is safe and effective, and the tumor responses outweigh the side effects of the drug. The mechanism of action of this compound is discussed.

Topics: Aged; Bone Neoplasms; Carcinoma; Diethylstilbestrol; Humans; Hydronephrosis; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Aged; Diethylstilbestrol; Estrogens; Humans; Injections, Intramuscular; Male; Multiple Myeloma; Prostatic Neoplasms

Topics: Diethylstilbestrol; Geriatrics; Humans; Injections; Injections, Intravenous; Male; Neoplasms; Palliative Care; Prostatic Neoplasms; Urinary Retention; Urination Disorders

Topics: Acid Phosphatase; Chlorotrianisene; Diethylstilbestrol; Humans; Injections, Intravenous; Male; Neoplasm Metastasis; Neoplasms; Palliative Care; Prostatectomy; Prostatic Neoplasms; Toxicology; Urination Disorders

Topics: Diethylstilbestrol; Geriatrics; Humans; Male; Neoplasms; Prostatic Neoplasms

Topics: Diethylstilbestrol; Gonadotropins; Gonadotropins, Pituitary; Humans; Male; Pituitary Diseases; Pituitary Gland; Prostatic Neoplasms; Testis

Topics: Carcinoma; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Diethylstilbestrol; Diphosphates; Humans; Male; Prostatic Neoplasms

Topics: Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Diethylstilbestrol; Diphosphates; Humans; Male; Prostatic Neoplasms

Topics: Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Cytostatic Agents; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Administration, Intravenous; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Antineoplastic Agents; Carcinoma; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Carcinoma; Diethylstilbestrol; Humans; Male; Neoplasms; Prostatic Neoplasms

Topics: Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Diethylstilbestrol; Humans; Male; Phosphorus; Phosphorus, Dietary; Prostatic Neoplasms; Radioactivity

Topics: Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Carcinoma; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Carcinoma; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms