fosfestrol and Bone-Neoplasms

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

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

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

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

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

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

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

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