Treatment of stage D hormone-resistant carcinoma of the prostate with estramustine phosphate.

We report on 51 patients with hormone-resistant, stage D prostatic carcinoma who were treated with estramustine phosphate and followed for at least 6 months. Of the 51 patients 5 (10 per cent) had a partial objective response, 30 (59 per cent) remained stable and 16 (31 per cent) had progression of the disease. All of those patients who had a partial response or remained stable also experienced subjective improvement as judged by relief of pain and performance status. Approximately 8 per cent of the patients will be unable to take estramustine phosphate because of intolerable gastrointestinal side effects.     

Treatment of advanced carcinoma of the prostate with estramustine phosphate.

Estramustine phosphate has been useful in the treatment of advanced carcinoma of the prostate. Objective remissions were obtained with this therapy in 6 of 17 patients (35 per cent). The results presented herein indicate that the clinical response is to a certain extent caused by an estrogen effect, which was clearly demonstrable in a previously untreated patient. A specific cytostatic effect of estramustine phosphate, which is not yet clearly explained, may be responsible for remissions in some patients who have become resistant to conventional hormonal treatment.     

The treatment of oestrogen-escaped carcinoma of the prostate with estramustine phosphate.

30 patients with oestrogen-escaped carcinoma of the prostate have been treated with estramustine phosphate (Estracyt). 27% showed a partial objective response and 33% had a subjective response. The terms used for defining a response are challenged and it is recommended that comparative controlled trials are necessary to judge the place of this drug in the management of advanced prostatic cancer.     

磷酸雌二醇氮芥联合足叶乙甙治疗激素抵抗性前列腺癌

目的观察磷酸雌二醇氮芥(EMP)联合足叶乙甙(Vp16)治疗激素抵抗性前列腺癌的疗效.方法2000年1月至2004年6月对12例全雄激素阻断治疗失败、排除氟他胺撤药综合征的激素抵抗性前列腺癌患者行EMP加Vp16联合化疗.患者年龄61～82岁,平均70岁.病理分级G23例,G39例.其中骨转移10例,软组织转移4例(肺转移2例,淋巴结转移2例).化疗方案EMP 560 mg/d,Vp16 50 mg·m-2·d-1,连续口服21 d,28 d为1个周期.直至病情进展或毒副反应无法耐受.疗效判断标准血PSA下降＞50%且维持＞1个月为有效;软组织转移灶疗效分为完全缓解、部分缓解、稳定和进展.结果12例随访6～24个月,平均12个月.PSA有效率50%(6/12),有效患者PSA从治疗前(63.9±47.3)ng/ml下降至(14.4±8.8)ng/ml,平均有效时间7.5个月.软组织转移灶部分缓解者2例,转移灶分别从治疗前的4.0 cm×5.0 cm,3.0 cm×3.5 cm缩小为2.0cm×2.0 cm,1.0 cm×1.5 cm,有效时间分别为3、8个月.毒副反应包括Ⅰ度血白细胞减少1例,Ⅰ度贫血1例,Ⅰ度脱发1例,Ⅰ度恶心2例,Ⅱ度肝功能损害1例.结论EMP加Vp16治疗激素抵抗性前列腺癌有一定疗效,毒副反应轻.     

Oral estramustine phosphate and oral etoposide for the treatment of hormone-refractory prostate cancer

BACKGROUND: The purpose of the present study was to evaluate the antitumor activity and toxicity of oral estramustine phosphate (EMP) in combination with oral etoposide in patients with hormone-refractory prostate cancer. METHODS: Twenty patients with adenocarcinoma of the prostate that progressed after one or more regimens of androgen-deprivation therapy were enrolled into this trial. Oral EMP was administered twice daily, for a total daily dose of 560 mg, and oral etoposide (50 mg/bodyweight per day) was given on days 1-21 and was stopped on days 22-35. Treatment was continued until evidence of disease progression appeared or two consecutive rises in the prostate-specific antigen (PSA) value were observed. RESULTS: Ten of 20 patients showed a decrease of 50% or greater in the PSA value from initially elevated PSA levels after therapy. The median progression-free duration and 2 year cause-specific survival rate of these 10 patients were 208 days (range 71-693 days) and 67.5%, respectively. There were no significant differences in age, pretreatment PSA value, duration from initial treatment to relapse, prior therapy or survival between patients who had a decrease of 50% or greater in PSA values after this combination therapy and those who did not. The main toxicities (> or =grade 2) were anemia, leukocytopenia, thrombocytopenia, gastrointestinal and hepatic disorders, which occurred in 40, 15, 10, 15 and 5% of patients, respectively. CONCLUSIONS: The combination of oral EMP and etoposide is considered to be a well-tolerated outpatient treatment regimen for patients with hormone-refractory prostate cancer and the therapy deserves further investigation.     

Oral estramustine phosphate and oral etoposide for the treatment of hormone-refractory prostate cancer

A total of 42 patients with hormone-refractory prostate cancer received E-E therapy. Oral estramustine phosphate (EMP) was administered twice daily for a total daily dose of 560 mg every day and oral etoposide (E-E therapy, 50 mg/body/day) was given on days 1-21 and stopped on days 22-35. Treatment was continued until the disease progression was confirmed radiographically or PSA had increased from base line of at least 25%. The median follow-up period after E-E therapy was 77.4 months (range : 12.5 to 122.3). Nineteen patients (43%) achieved a PSA decrease of 50% or greater. The median survival time of the patients who had a decrease of 50% or greater in the PSA value (PSA responder) was 29.3 months and the patients who did not (PSA non-responder) was 14.1 months (p = 0.01). There were no significant differences between PSA responders and non-responders when taking into account variables. Excluding those patients with only PSA elevation, the survival time was 14.9 months with no significant difference between PSA responders and non-responders. The toxicities (grade 3 or more) were identified as anemia, leukocytopenia thrombocytopenia, cardiovascular events, and gastrointestinal and hepatic disorders, which occurred in 0, 5, 2, 2, 14, and 2% of the patients, respectively. E-E therapy was considered to be an active oral regimen and well-tolerated for outpatients with hormone-refractory prostate cancer in Japanese patients.     

Effect of estramustine phosphate on plasma testosterone during treatment of carcinoma of prostate

Estramustine phosphate administered orally at 900 mg. daily depressed plasma testosterone levels in 10 consecutive patients who had previously been treated with estrogen hormones and/or orchiectomy and who were all in relapse from carcinoma of the prostate. Approximately one half of the patients responded to the treatment clinically. The decrease in plasma testosterone did not correlate with the clinical response. The clinical effect of estramustine phosphate may be due to decreased plasma testosterone levels, inhibition of 5-alpha reductase activity, and a local cytotoxic effect.     

Extended follow-up of stage A1 carcinoma of prostate

The prognosis and proper treatment of Stage A1 carcinoma of the prostate remain unsettled. We report on 60 patients with Stage A1 prostate cancer (less than 5 foci of well-differentiated tumor) diagnosed between 1960 and 1980. Mean duration of follow-up was 7.5 years with a range of one to twenty years. Three patients (5%) suffered disease progression at two, five, and nineteen years of follow-up, and all died of their tumor. Thirty-four patients (56%) have died of other causes. Number of tumor foci had no correlation with chance of disease progression. Extended follow-up of these patients suggests that the vast majority with Stage A1 carcinoma of the prostate will not suffer from morbidity or mortality of the disease but will more commonly succumb to other intervening disease processes.     

Primary treatment of prostatic carcinoma with estramustine phosphate: preliminary report.

Estramustine phosphate has been used as primary treatment in 38 patients with advanced prostatic carcinoma. Of these 38 patients 36 responded objectively to treatment, regression occurring in 10 patients with soft tissue metastases, 3 with pulmonary metastases and 3 with bony metastases. Primary cytotoxic treatment in patients with far advanced prostatic carcinoma is advocated and a randomized clinical study is suggested.     

Intermittent oral hormonal chemotherapy using estramustine phosphate and etoposide for the treatment of hormone-refractory prostate cancer

Seventeen patients were given lower dose and intermittent oral administration of estramustine phosphate (6 mg/kg/day) and etoposide (30 mg/m2/day) for 7 days. Then administration was discontinued for 7 days. This administration cycle was repeated. Therapy was continued until evidence of disease progression or unacceptable toxicity occurred. Fifteen of the 17 patients were finally evaluated for PSA response. Overall, the pretreatment PSA levels were lowered at least 50% from baseline in 7 (47%) of the 15 patients. The median survival was 65 weeks. Five of the 17 patients complained of anorexia or nausea during the treatment, but none of them showed over grade 2 anorexia, none requiring transfusion or hospitalization. None of the patients showed edema, deep venous thrombosis, thrombocytopenia, anemia or myocardial infarction. Because of its rare and mild adverse effects, this intermittent administration of oral estramustine and oral etoposide may be a useful and secure regimen for hormone refractory prostate cancer.     

Treatment of estrogen-resistant stage D carcinoma of prostate with cis diamminedichloroplatinum.

Forty-five patients with rapidly progressive, estrogen-resistant Stage D adenocarcinoma of the prostate were treated with infusions of cis diamminedichloroplatinum (cis platinum) (1 mg./Kg./week) for six weeks initially and every three weeks thereafter. A partial objective response was observed in 13 of 45 patients (29 per cent). This response lasted from two to sixteen months with an average of six months. Eighteen patients (40 per cent) had a significant decrease or disappearance of bone pain and became ambulatory. Six patients (13 per cent) remained stable, and 8 patients (18 per cent) did not respond to treatment and showed progression of their disease. The toxicity of the treatment was mild to moderate. Most of the patients were treated in the outpatient department. Cis platinum appears to be the most effective drug available to date for the treatment of advanced carcinoma of the prostate.     

Hydroxyurea in stage D carcinoma of prostate

Thirty patients with histologically proved metastatic prostatic adenocarcinoma Stage D were treated with a single oral dose of 80 mg. per Kg. hydroxyurea every third day (based on ideal or actual weight, whichever is less) and 12 mg. chlorotrianisene per day. Toxicity was mild. The most common manifestations were nausea, occasional vomiting, and leukopenia. A definite attempt was made to depress the white blood count to approximately 2,000 cells per cu. mm. Hydroxyurea was not discontinued unless the white blood count decreased to less than 2,000 cells per cu. mm., after which a single dose was usually omitted. Omission of a single dose would allow the white blood count to return promptly to more than 2,000 cells per cu. mm. Objective tumor regression was demonstrated in 15 of the 30 patients, and most patients had a definite improvement in the quality of life.     

Hormonal management of stage D carcinoma of the prostate

A variety of new agents is available for the hormonal treatment of prostatic cancer. None of these agents has shown itself to be superior to bilateral orchiectomy, but their individual side effects profiles may make one more appealing than another. Total androgen ablation may offer a slight survival advantage over partial androgen ablation, but this must be weighed in terms of increased side effects and overall cost. Hormonal therapy remains an effective palliative but not curative means of treating advanced prostatic cancer.     

Prospective study of estramustine phosphate for hormone refractory prostate cancer patients following androgen deprivation therapy

INTRODUCTION: Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint. METHODS: After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5-540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared. RESULTS: Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2-18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2-45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029). CONCLUSIONS: Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate.     

Treatment of advanced prostatic carcinoma with estramustine phosphate (Estracyt).

Estramustine phosphate (Estracyt) was used in the treatment of 154 patients with carcinoma of the prostate in stage IV. Sixty-three patients were given Estracyt from the outset (primary treatment group) and 91 had previously received some other endocrine therapy (secondary treatment group). All of the patients were observed for more than one year. The drug was given intravenously and/or orally. Objective remissions occurred in 46 (73.0%) of the 63 patients in the primary treatment group and subjective remissions in all the objective responders and in 12 additional patients (92.0%). The corresponding figures for the secondary treatment group were 28 (30.7%) and 52 (57.1%) of 91. The side-effects were negligible, and the drug was well tolerated. No cumulative toxic effect was observed in patients who had been receiving the treatment for more than five years. In our opinion the compound is valuable in the treatment of advanced prostatic carcinoma (stage IV).     

Chemo-endocrine therapy in patients with stage D2 prostate cancer

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.     

Clinical evaluation of estramustine phosphate and vinblastine in patients with hormone-refractory prostate cancer

We evaluated the efficacy of the combination of estramustine phosphate and vinblastine in 13 patients with hormone-refractory prostate cancer. Of 12 patients with an elevated prostate specific antigen (PSA) level at the start of treatment, 5 (42%) had a greater than 50% decrease in PSA level. In a patient with cervical and mediastinal lymph node metastases, about a 57% decrease was observed in bidimensional measurement. Side effects were mild and manageable. The survival rate was not significantly different between patients who showed a greater than 50% decrease in PSA levels or regression of lymph node metastases versus the other patients.     

Hormone-resistant metastatic prostate cancer. Comparisons between estramustine phosphate and low-dose epirubicin treatments.

We compared the effect and toxicity of estramustine phosphate and weekly low-dose epirubicin in a prospective randomized trial in 41 patients with metastatic prostate cancer refractory to hormonal manipulation. No significant difference between treatment modalities was seen. Palliation was reached in over 60% of patients. The median survival was 15 months in both groups. Toxicity was mild. Further, we investigated the effect of epirubicin after the failure of preceding estramustine phosphate therapy in additional 20 patients. Pain relief was achieved in 50% of these patients. The median survival was 10 months. Toxicity was acceptable.     

Hydroxyurea in stage D carcinoma of the prostate: a pilot study.

There was 13 patinets with histologically metastatic prostatic adenocarcinoma treated with a single oral dose of 80 mg. per kg. hydroxyurea every third day (based on ideal or actual weight, whichever is less) and 12.5 mg. chlorotrianisene per day. Toxicity was mild. The most common manifestations were nausea, occasional vomiting leukopenia. A definite attempt was made to depress the white blood count to approximately 2,000 cells per cu. mm. Hydroxyurea was not discontinued unless the white blood count decreased to less that 2,000 cells per cu. mm., after which a single dose was usually omitted. Omission of a single dose would allow the white blood count to return promptly to more than 2,000 cells per cu. mm. Objective tumor regression was demonstrated in 6 of the 13 patients and all patients had a definite improvement in the quality of life.     

Prognosis of patients with stage D1 prostate carcinoma following radical prostatectomy with and without early endocrine therapy

Early endocrine therapy after radical retropubic prostatectomy was compared to radical prostatectomy alone (nonearly endocrine therapy) for the treatment of carcinoma of the prostate with lymph node metastases. Our retrospective analysis demonstrated that the 2 cohorts were similar with respect to patient age, Gleason sum score, seminal vesicle invasion, lymph node involvement, tumor volume and pathological stage of the primary tumor. The cause-specific survival of the entire group was 84% at 60 months and 78% at 98 months. The cause-specific curves for the early and nonearly endocrine therapy group were not significantly different (p less than 0.194), although the estimated 9-year survival rates were 91 and 71%, respectively. Survival free of disease was significantly prolonged in the early endocrine therapy group (p less than 0.030), with a 9-year estimated rate free of disease of 67% versus 32% in the nonearly endocrine therapy group. Followup prostate specific antigen serum levels were analyzed and the value as a progression marker is discussed. These data suggest that a radical operation plus early endocrine therapy is effective palliation in selected patients with low volume lymph node metastases, producing clinical survival free of disease in most patients.