estramustine and Bone-Neoplasms

If androgen deprivation, chemical with LH-RH analogs or surgical with bilateral orchiectomy, still remains the stone edge of treatment of prostate cancer, in the metastatic setting, this hormonosensitivity, most of the time long, finally move on in hormonal-failure. If rare changes in the therapeutic strategy have been achieved in this setting since 2004 and the arrival of docetaxel, it is the global perception of the disease that has been modified and the definition of one specific entity: the castrate-resistant prostate cancer. This new definition and the changes of design and end-points of clinical trials testing new agents with strong recruitment during the past years have conducted to a real revolution in the management of castrate-refractory prostate cancer. The place of secondary hormonal manipulations, such as withdrawal of the anti-androgen, oestrogen or ketoconazole, still exists for a selected group of patients. In case of aggressive disease and symptoms, chemotherapy should be selected, docetaxel, in a three weeks schedule, and may be combined with Estracyt. It is time to consider the revolution of the post-chemotherapy setting with the arrival of two new drugs ; a cytotoxic one, the cabazitaxel and hormonal for the second one, the abiraterone acetate. The place of the immunotherapy with the sipuleucel-T may be more difficult to precise, especially in Europe, even if it has been finally indicated in the United States in the metastatic setting. Concerning bone metastasis, zoledronic acid was during a long time the only bone-targeted agent, effective in reducing the incidence of skeletal related events, and was recently exceeded by the denosumab, an anti-RANK ligand. Finally, let us hope that other changes will be achieved in the near future, with the cabazitaxel-docetaxel confrontation in the first-line setting, and the introduction of the abiraterone acetate before chemotherapy with docetaxel, already tested in ongoing trials.

Topics: Abiraterone Acetate; Androgen Antagonists; Androstadienes; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bone Density Conservation Agents; Bone Neoplasms; Cancer Vaccines; Denosumab; Diphosphonates; Docetaxel; Estramustine; Humans; Imidazoles; Male; Orchiectomy; Prostatic Neoplasms; Taxoids; Tissue Extracts; Zoledronic Acid

The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bone Neoplasms; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Dexamethasone; Drug Resistance, Neoplasm; Estramustine; Etoposide; Gonadotropin-Releasing Hormone; Growth Substances; Humans; Leuprolide; Male; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Orchiectomy; Osteoblasts; Osteoclasts; Paracrine Communication; Peptides, Cyclic; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Receptors, Androgen; Salvage Therapy; Somatostatin; Survival Analysis; Triptorelin Pamoate

Prostate cancer is the most common malignancy in men in the United States. With the long natural history of the disease, management of skeletal morbidity related to advanced prostate cancer becomes a major public health issue. The standard of care in advanced prostate cancer is androgen deprivation therapy. This may accelerate the development of osteoporosis and further exacerbate the risks of having adverse skeletal-related events develop. Recently, the use of bisphosphonates in men who have not responded to androgen deprivation therapy has been shown to reduce the incidence of skeletal-related events with time. Questions remain as to whether bisphosphonates should be broadly applied to earlier stages of the disease or tailored to men at higher risk of having bone-related morbidity. Work is ongoing to improve other approaches to the medical treatment of bone metastases in patients with advanced prostate cancer including the use of radiopharmaceuticals and combined chemotherapy.

Topics: Antineoplastic Agents, Hormonal; Bone Density; Bone Neoplasms; Diphosphonates; Disease Progression; Estramustine; Fractures, Spontaneous; Gonadotropin-Releasing Hormone; Humans; Hyperparathyroidism; Male; Prostatic Neoplasms

Topics: Androgens; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Clinical Trials as Topic; Clodronic Acid; Cyclophosphamide; Dexamethasone; Docetaxel; Estramustine; Humans; Male; Neoplasms, Hormone-Dependent; Paclitaxel; Prostatic Neoplasms; Strontium Radioisotopes; Taxoids; Tegafur; Treatment Outcome

Although the penis is highly vascularized, secondary penile tumors are rare and 28% of these metastasize from prostatic tumors. Urethral metastases are uncommon and may be caused by seeding following manipulation of the prostate with instruments or spread directly from the adjacent structures. This condition can be controlled and treated effectively with first or second line hormone therapy. Herein we describe a 65-year-old male with disseminated prostatic adenocarcinoma who presented multiple urethral metastases that were successfully treated with stramustine phosphate.

Topics: Adenocarcinoma; Aged; Biopsy; Bone Neoplasms; Estramustine; Humans; Male; Prostatic Neoplasms; Remission Induction; Urethra; Urethral Neoplasms

Until today, docetaxel is the only EMEA and FDA approved active agent in hormone refractory prostate cancer (HRPC). In the absence of other effective and approved drugs we evaluated the toxicity and efficacy of intermittent-docetaxel-chemotherapy in patients whose cancers progressed after successful first-line docetaxel therapy.. 46, 18, and 5 patients with HRPC received 1, 2, or 3 cycles of docetaxel based chemotherapy. Toxicity, PSA response and general condition were evaluated systematically. SPSS 15.0 was applied for statistic analysis.. 26 (56 %) patients achieved a PSA response of > 50 %, another 10 (22 %) patients of up to 50 %; 10 (22 %) patients were progressive under docetaxel. The median overall survival of the whole cohort calculated from the first docetaxel application was 16 (3-60 +) months. Tolerance, toxicity and general condition were crucial for the administration of a second cycle (n = 18); in contrast, age or the degree of the PSA decline in cycle 1 did not seem to be of importance. The -median overall survival of all patients who -received at least two blocks was 35 months; more-over, 13 / 18 patients achieved a biochemical response in cycle 2. Toxicity did not rise significantly. Five patients were given a third docetaxel cycle, three of whom responded. Higher frequencies of -grade 3 / 4 stomatitis, skin toxicity and leukocytopaenia were observed.. Intermittent docetaxel therapy is well tolerated and shows high response rates in the sec-ond and third sequences of treatment in select-ed HRPC patients who presented with low docetaxel toxicity, good clinical condition and responded to prior docetaxel-based treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Disease Progression; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Estramustine; Humans; Male; Middle Aged; Mitoxantrone; Neoplasm Staging; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Retreatment; Survival Rate; Taxoids

Bone-targeted therapy that combines strontium-89 (Sr-89) with alternating weekly chemohormonal therapy may improve clinical outcomes in patients with metastatic hormone-refractory prostate cancer. This phase II study investigated the addition of Sr-89 to an alternating weekly regimen of doxorubicin and ketoconazole with paclitaxel and estramustine in patients with progressive prostate cancer and bone involvement.. Twenty-nine patients with progressive adenocarcinoma of the prostate and osteoblastic bone metastases who failed conventional hormonal therapy were registered for the study. Of those, 27 were treated with Sr-89 on day 1 of week 1. On weeks 1, 3, and 5, patients received doxorubicin (20 mg/m on day 1) and oral ketoconazole (400 mg 3 times a day for 7 days). On weeks 2, 4, and 6, patients received paclitaxel (100 mg/m(2)) and oral estramustine (280 mg 3 times a day for 7 days). No treatment was given during weeks 7 and 8. Cycles were repeated every 8 weeks.. A > or =50% reduction in prostate-specific antigen level was maintained for at least 8 weeks in 77.7% of the patients (21 patients) at 16 weeks and in 66.6% (18 patients) at 32 weeks. The median progression-free survival was 11.27 months (range, 1.83-29.53), and the median overall survival was 22.67 months (1.83-57.73+). Two patients died during study because of disease progression. Overall, the chemotherapy combined with Sr-89 was well tolerated.. Our results demonstrate that the combination of alternating weekly chemohormonal therapies with Sr-89 demonstrates a prolonged progression-free and overall survival with acceptable toxicity. Further investigation of combination therapies with Sr-89 is warranted.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Doxorubicin; Estramustine; Humans; Ketoconazole; Male; Middle Aged; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Strontium Radioisotopes; Survival Rate; Treatment Outcome

Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen.

Topics: Administration, Oral; Aged; Aged, 80 and over; Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Diphosphonates; Docetaxel; Drug Administration Schedule; Drug Resistance, Neoplasm; Estramustine; Fatigue; Humans; Hypocalcemia; Imidazoles; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids; Thrombocytopenia; Time Factors; Treatment Outcome; Zoledronic Acid

Docetaxel/estramustine was a commonly used regimen to treat metastatic hormone-refractory prostate cancer. Imatinib inhibits the platelet-derived growth factor receptor that is expressed in prostate cancer and is synergistic with taxanes in preclinical prostate cancer models.. A phase I trial of docetaxel/estramustine/ imatinib was undertaken to determine the safety and maximum tolerated dose of this combination. Patients with progressive, metastatic, hormone-refractory prostate cancer were treated every 21 days with fixed doses of estramustine (280 mg orally 3 times a day on days 1-5), imatinib (400 mg orally daily on days 1-21), dexamethasone (8 mg orally twice daily on days 1-3), and prophylactic warfarin (2 mg orally daily on days 1-21). Cohorts of 3-6 patients were enrolled to receive escalating doses of docetaxel on day 2 from 50 mg/m2 to 60 mg/m2 to 70 mg/m2. Thirteen patients were treated.. On dose level 3 (docetaxel 70 mg/m2 and imatinib 400 mg daily), 2 patients experienced grade 3 elevations in prothrombin time, attributed to the interaction between imatinib and warfarin. The protocol was amended to include an intermediate dose level (docetaxel 60 mg/m2 and imatinib 300 mg daily). However, in the overall study, there were 5 unacceptable toxicities (2 cerebrovascular accidents, 1 myocardial infarction, 1 mesenteric ischemia, and 1 deep venous thrombosis) in 13 patients; 2 of those toxicities resulted in death. The study was closed early to further accrual.. The high incidence of thromboembolic events observed when imatinib was combined with docetaxel/estramustine precludes further exploration of this regimen.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Bone Neoplasms; Disease Progression; Docetaxel; Estramustine; Humans; Imatinib Mesylate; Male; Middle Aged; Piperazines; Prostate-Specific Antigen; Prostatic Neoplasms; Pyrimidines; Survival Rate; Taxoids; Treatment Outcome

The primary objective of this study was to assess the feasibility and efficacy of administering etoposide/estramustine/paclitaxel in hormone-sensitive metastatic prostate cancer responding to hormonal therapy.. Eligible patients had metastatic prostate cancer and had received combined androgen blockade for 6-8 months with a > or = 80% decrease in prostate-specific antigen from pretreatment. They received 4 cycles of chemotherapy consisting of estramustine 280 mg orally 3 times daily, etoposide 50 mg/m2 orally on days 1-14, and paclitaxel 135 mg/m2 intravenously for 1 hour on day 2 of each 21-day cycle and were then followed until time to treatment failure (TTF).. Twenty-six patients were evaluable for response and toxicity. Median TTF was 21.7 months (range, 11.9-64.5 months; 95% confidence interval, 15.3-26.2 months). Median survival from time of initiation of hormone therapy was 5.1 years. Neutropenia was the most common grade 3/4 toxicity, occurring in 3 patients. Significant toxicities were limited to nausea, diarrhea, and febrile neutropenia in 3 patients, respectively.. The administration of paclitaxel/estramustine/etoposide in this setting is feasible and well tolerated. Although the TTF of 21.7 months by prostate-specific antigen criteria is similar to historical controls in the emergence of clinically evident androgen-independent disease after starting hormone therapy, direct comparisons cannot be made. More trials are needed to investigate the timing of chemotherapy in patients with prostate cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Disease Progression; Estramustine; Etoposide; Feasibility Studies; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasms, Hormone-Dependent; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Treatment Outcome

The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m(-2) of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1-3, 8-10, 15-17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1-9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44-72) and median duration of PSA response was 8.0 months (95% CI: 6.9-9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Celecoxib; Disease Progression; Docetaxel; Drug Administration Schedule; Estramustine; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prospective Studies; Prostatic Neoplasms; Pyrazoles; Soft Tissue Neoplasms; Sulfonamides; Survival Rate; Taxoids

Palliation of bone pain can be achieved in men with androgen-independent prostate cancer treated with docetaxel and estramustine (DE) or mitoxantrone and prednisone (MP). While Southwest Oncology Group trial 99-16 demonstrated a survival improvement of DE over MP, the study also was designed to compare the palliation of disease-related symptoms.. Pain palliation and global quality of life (QOL) were the two primary patient-reported outcomes. Pain was measured with the Present Pain Intensity scale of the McGill Pain Questionnaire-Short Form. The European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (QLQ-C30) and its Prostate Cancer Module (PR25) measured QOL and symptom status. Pain and analgesic use were measured at random assignment, every cycle for eight cycles, and 1 year from random assignment; the QLQ-C30 and the PR25 were administered at random assignment, before cycle four (week 10) and cycle eight (month 6) and at 1 year. In addition to the primary intent-to-treat, missing at random analysis, sensitivity analyses were performed to assess robustness of global QOL conclusions under alternative informative missing data assumptions.. Six hundred seventy four eligible patients received DE (n = 338) or MP (n = 336). In an intention-to-treat analysis, median overall survival was 17.5 months for the DE arm and 15.6 months for the MP arm (P = .02). There were no statistically significant differences in pain palliation between the treatment arms. The sensitivity analyses showed a consistent lack of statistically significant global QOL differences for the two arms.. DE had superior clinical efficacy (overall survival, time-to-progression, and prostate-specific antigen declines) with similar global QOL and pain palliation in the MP arm.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Docetaxel; Estramustine; Humans; Male; Middle Aged; Mitoxantrone; Pain; Pain Measurement; Palliative Care; Prednisone; Prostatic Neoplasms; Quality of Life; Survival Analysis; Taxoids

We determined the safety and preliminary efficacy of the combination of high dose pulse calcitriol (1,25-dihydroxycholecalciferol) with a standard regimen of docetaxel plus estramustine in patients with metastatic androgen independent prostate cancer.. Patients were treated with 60 microg calcitriol orally on day 1, 280 mg estramustine orally 3 times daily on days 1 to 5 and 60 mg/m docetaxel on day 2 (70 mg/m after cycle 1) every 21 days for up to 12 cycles. Patients also received 325 mg aspirin and 1 or 2 mg warfarin orally daily. Regimen safety was assessed in the first 6 patients and a dose de-escalation scheme for calcitriol was planned if dose limiting toxicities were noted during treatment cycle 1 in greater than a third of patients.. A total of 24 patients, including 11 who were chemotherapy naïve and 13 who had previously been treated with docetaxel, were evaluable for toxicity and 22 for prostate specific antigen decrease data. The regimen was generally well tolerated. Treatment related grades 3 or greater toxicity seen in more than 1 patient included hypophosphatemia in 16.7% and neutropenia in 12.5%. Four patients had thromboembolic complications. Asymptomatic hypercalcemia was seen in 4 patients, including grades 2 and 1 in 1 and 3, respectively. Six of 11 evaluable, chemotherapy naïve patients (55%) met prostate specific antigen response criteria. One of 11 patients (9%) treated with prior docetaxel met these criteria.. High dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Calcitriol; Disease Progression; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Estramustine; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids; Treatment Outcome

To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC.. Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups.. The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant).. The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Dexamethasone; Diabetes Mellitus; Disease-Free Survival; Estramustine; Etoposide; Gastrointestinal Diseases; Gonadotropin-Releasing Hormone; Hematologic Diseases; Humans; Life Tables; Male; Middle Aged; Orchiectomy; Peptides, Cyclic; Prostatic Neoplasms; Somatostatin; Survival Analysis; Treatment Outcome; Triptorelin Pamoate

Paclitaxel used in combination with estramustine has been shown to exert synergistic cytotoxicity in patients with hormone-refractory prostate cancer (HRPC). There have been few reports of this therapy in an Asian male population.. Nine patients with progressive metastatic HRPC completed at least one cycle of combination therapy employing weekly paclitaxel plus estramustine. Paclitaxel was given weekly for 3 weeks as a 2-h intravenous infusion at a dose of 100 mg/infusion. The cycle was repeated every 4 weeks. A dose of 280 mg of oral estramustine was administrated twice daily for 21 days from the first day of each cycle. Both efficacy and toxicity were recorded.. Grade 1 sensory neuropathy was seen in three patients (33%) and grade 4 thrombopenia/anemia was seen in one patient (11%). Performance status improved in three of seven patients (43%), while six patients (67%) showed a 50% or greater decline in prostate-specific antigen levels. Two of these patients experienced significant improvement in bone pain. One patient died of cardiac infarction during this trial and another died of disseminated intravascular coagulopathy subsequent to gastrointestinal bleeding. An additional patient suffered non-fatal pulmonary infarction. The one-year median survival rate was 22.2% and the overall survival period was 36 weeks.. Although weekly paclitaxel plus estramustine may pose a significant risk, this combination may have a beneficial effect on the quality of life HRPC patients. A well-designed phase I-II trial in an Asian male population is highly recommended.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Drug Administration Schedule; Estramustine; Humans; Infusions, Intravenous; Lymphatic Metastasis; Male; Middle Aged; Paclitaxel; Pain; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

Several trials have demonstrated that the response proportions to microtubule agents in patients with prostate cancer are increased by the addition of estramustine phosphate (EMP). The epothilone B analog BMS-247550 is a novel microtubule agent that has shown activity in taxane-resistant tumors. We conducted a dose-escalation study to determine a safe dose of BMS-247550 to combine with EMP in patients with metastatic prostate cancer.. Chemotherapy-naive patients with castrate-metastatic prostate cancer were treated with intravenous BMS-247550 and oral EMP (280 mg three times daily for 5 days) every 3 weeks.. Thirteen patients were treated at two dose levels (35 and 40 mg/m(2)). Three of six patients treated at 40 mg/m(2) developed grade 4 neutropenia, establishing 35 mg/m(2) as the maximum-tolerated dose. Significant peripheral neuropathy (grade >/= 2) was related to dose level and infusion rate. A decline in prostate-specific antigen (PSA) of >/= 50% was seen in 11 of 12 evaluable patients (92%) (95% confidence interval 76% to 100%). There were objective responses in soft tissue (57%) and bone metastasis (40%).. The phase II dose of BMS-247550 combined with EMP is 35 mg/m(2) over 3 h every 3 weeks. This combination is safe and >/= 50% post-therapy declines in PSA were seen in 11 of 12 patients (92%).

Topics: Adenocarcinoma; Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Bone Neoplasms; Castration; Dose-Response Relationship, Drug; Epothilones; Estramustine; Humans; Male; Maximum Tolerated Dose; Microtubules; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

The combination of paclitaxel, oral estramustine phosphate (EMP), and carboplatin (TEC) has shown antitumor activity in patients with castrate, metastatic prostate carcinoma. To improve the therapeutic efficacy and reduce the toxicity of TEC, the authors substituted intravenous (i.v.) EMP for oral EMP based on single-agent studies demonstrating an improved safety profile with i.v. EMP.. Patients with progressive, castrate, metastatic prostate carcinoma were treated with up to 6 4-week cycles of i.v. EMP (500-1500 mg/m(2) per week), paclitaxel (100 mg/m(2) per week), and carboplatin (target area under the curve = 6 mg/mL every 4 weeks).. Thirty patients were treated in 6 dose cohorts. Deep venous thrombosis occurred in 5 of 30 patients (17%). Other common Grade 3/4 (according to National Cancer Institute Common Toxicity Criteria) toxicities included hepatic toxicity (23%) and leukopenia (24%). Posttherapy prostate specific antigen declines > 50% were seen in 18 of 30 patients (60%), and declines > 80% were seen in 15 of 30 patients (50%). Eleven of 17 patients (65%) with measurable soft tissue disease achieved a partial response. Four of 27 patients (15%) with osseous metastases demonstrated improvement on bone scan.. Intravenous EMP was administered safely with paclitaxel and carboplatin and produced clinical outcomes similar to the outcomes achieved with the TEC regimen. Substitution of i.v. EMP for the oral formulation was found to result in a lower incidence of severe nausea but increased hepatic toxicity.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carboplatin; Disease-Free Survival; Drug Administration Schedule; Estramustine; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasm Metastasis; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

The purpose was to evaluate the combined anti-microtubular regimen of vinorelbine and estramustine phosphate (EMP) in hormone refractory prostate cancer.. Weekly vinorelbine 20 mg/m2 (or 15 mg/m2 if a history of prior pelvic radiotherapy) was combined with EMP at 280 mg orally tds for 3 days (the day before, the day of and the day after vinorelbine infusion). After 8 weeks of therapy the combination was given every other week.. From February 1998 to February 1999, 23 men were enrolled with a median age of 69 years (range 50-83 years). The median prostate-specific antigen (PSA) at entry was 160 ng/ml (range 0-802 ng/ml). A median of 13 weeks of therapy was administered and the median follow-up was 14.8 months. Eleven patients (48%) had lower extremity edema requiring diuretic therapy, two (9%) had grade 2 granulocytopenia and four patients [17%; 95% confidence interval (CI) 5% to 39%] had a thromboembolic episode. There was no treatment-related mortality. Fifteen of 21 patients (71%; 95% CI 49% to 89%) had at least a 50% decrease in the PSA for at least 2 months with a median time to serologic progression of 3.5 months (range 0.75-10.5 months). One of eight patients (12.5%; 95% CI 0% to 53%) with measurable disease had a confirmed partial response. The estimated median survival was 15.1 months and the actual one year overall survival was 71% (95% CI 51% to 88%).. Weekly vinorelbine with short course oral EMP is an active regimen as evaluated by rate of PSA response, time to progression and median survival. However, the toxicities of EMP, even when given as a short course, are still problematic.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Estramustine; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Survival Rate; Treatment Outcome; Vinblastine; Vinorelbine

To evaluate the clinical usefulness of an oral combination of cyclophosphamide, uracil plus tegafur (UFT) and estramustine in the treatment of patients with hormone-refractory prostate cancer (HRPC).. Twenty-one patients were treated with oral administration of cyclophosphamide (100 mg/day), UFT (400 mg/day) and estramustine phosphate (560 mg/day). The median age of the patients was 70 years. Twelve patients had symptomatic bone metastasis, 6 had asymptomatic bone metastasis, 5 had lymph node metastasis, while 2 had only biochemical progression evaluated by prostate-specific antigen (PSA).. Twelve (57%) out of 21 patients showed a PSA decline of 50% or greater. The median response duration was 7 months (range 2-15 months). Among the 20 patients assessable for bone pain, 2 (10%) improved, 12 (60%) remained stable and 6 (30%) progressed. Among the 10 patients assessable for bone metastasis, 1 (10%) improved, 5 (50%) were stable and 4 (40%) progressed on bone scan. Among 3 patients assessable for measurable disease (lymph node metastasis), 2 (67%) showed partial response and 1 (33%) progression. Most toxicities were mild.. The combination of cyclophosphamide, UFT and estramustine is an active and well-tolerated regimen for HRPC. To evaluate the survival benefit, further randomized studies are required.

Topics: Administration, Oral; Aged; Aged, 80 and over; Androgen Antagonists; Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyclophosphamide; Estramustine; Humans; Lymphatic Metastasis; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Tegafur; Treatment Outcome; Uracil; Urination

There are limited data available regarding the cost of care in patients with androgen independent prostate carcinoma (AIPC), and there are no data on the impact of direct nonmedical and indirect costs (DNM/IC). This lack of data, along with the feasibility of collecting DNM/IC, was examined in patients with AIPC who took part in a randomized trial using a newly developed questionnaire, the Collection of Indirect and Nonmedical Direct Costs (COIN) form.. Patients with AIPC were randomized to one of three treatment arms: 1) strontium only (strontium 4 Mci in Week 1 and Week 12) (STRONT); 2) vinblastine 4 mg/m(2) per week for 3 weeks then 1 week off and estramustine, 10 mg/kg per day (CHEMO); or 3) a combination of treatments outlined in the arms for CHEMO and STRONT (CHEMO/STRONT). Direct medical costs were collected through the hospital billing system. DNM/IC data were obtained prospectively using the COIN form. Cost data were analyzed for a period of 6 months.. Twenty-nine patients were randomized, after which the protocol was closed because of poor accrual. The median survival of the patients was 22.3 months. The mean and median total costs for the 20 of 29 patients with complete cost information were $12,647 and $11,257 over 6 months, respectively. DNM/IC represented 11% of the total cost (range, from < 1% to 42%); in 20% of participating individuals, these costs accounted for 35-42% of total costs. Failure to collect complete cost information was due to early death, administrative difficulties, and loss to follow-up.. In this pilot project, the collection of these cost data using the COIN form was feasible and practical and was limited primarily by logistic, not form specific, issues. DNM/IC were found to be a significant proportion of total costs (up to 42%) in selected patients, and this information proved to be a useful addition to the cost analysis. Approximately 98 patients would be required to detect a 20% difference in total costs between arms in a properly powered, randomized trial. Considering the potentially significant impact on total costs, DNM/IC data should be included in future cost-analysis studies of patients with AIPC and other diseases.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Bone Neoplasms; Cost of Illness; Drug Costs; Estramustine; Health Care Costs; Health Expenditures; Hospital Costs; Humans; Male; Middle Aged; Pain; Pilot Projects; Prostatic Neoplasms; Strontium; Vinblastine

Nearly all cases of metastatic prostate carcinoma progress, after hormonal ablation, to a hormone refractory status. To the authors' knowledge no standard chemotherapy for patients with hormone refractory prostate carcinoma (HRPC) exists. In a prospective study, the efficacy and toxicity of an oral combination of estramustine and cyclophosphamide were evaluated.. Between March 1996 and April 1998, 32 consecutive patients (median age 74 years; range, 53-84 years) with metastatic HRPC were treated with oral estramustine (10 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day) for 14 days every 28 days. Inclusion criteria were previous complete androgen blockade, antiandrogen withdrawal evaluation, and clinical or biochemical disease progression. Response assessment was based on a decrease > or =50% in the prostate specific antigen (PSA) level associated with improvement (or no worsening) in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and relief of bone pain (if present).. All patients were evaluable for efficacy and toxicity. PSA levels decreased by at least 50% in 14 patients (43.7%) (95% confidence interval, 26.5-60.9), remained stable in 12 patients (37.5%), and rose in 6 patients (18.8%). ECOG PS was 0 in 5 of 14 patients, improved from 1 to 0 in 7 patients, and remained unchanged in 2 patients. Bone pain, present in 8 of 14 patients, disappeared in 7 and was partially relieved in 1. The median duration of response was 30 weeks (range, 8-88+ weeks). An objective partial response was obtained in two cases. Toxicity was mild and mainly gastrointestinal (World Health Organization [WHO] Grade 1). No cases of WHO Grade 3-4 hematologic toxicity occurred.. The oral combination of estramustine and cyclophosphamide appears to be safe and effective in patients with HRPC. In responding patients its use shows a clinical benefit in terms of improvement of ECOG PS and pain control.

Topics: Administration, Oral; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma; Chi-Square Distribution; Confidence Intervals; Cyclophosphamide; Disease Progression; Estramustine; Follow-Up Studies; Humans; Male; Middle Aged; Pain; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Safety

To apply our preclinical findings of cytotoxic synergy with the combination of estramustine phosphate (EP) and docetaxel as the basis of treatment of hormone refractory metastatic prostate cancer in man. To determine the optimal dosage and the toxicities of these two agents for future trials.. Seventeen patients with hormone refractory metastatic prostate cancer who were ambulatory with performance status < or = 2, normal marrow, renal and hepatic function were entered. Prior exposure to EP or a taxane were exclusion factors. EP was given orally at a dose of 14 mg/kg of body weight daily with concurrent docetaxel administered every 21 days as an intravenous infusion over 1 hour with dexamethasone 8 mg. PO BID for five days. EP dosages were kept static; docetaxel dosages were explored in a minimum of three patients per level for dosages of 40, 60, 70, and 80 mg/m2. Patients were evaluated weekly. Prostate specific antigen (PSA) was measured every three weeks.. Five patients were entered at a docetaxel dose of 40 mg/m2, three at 60 mg/m2, six at 70 mg/m2, and three at 80 mg/m2. Only one patient had received prior chemotherapy. Grades 1 or 2 hypocalcemia and hypophosphatemia were seen at all dosage levels. Other grade 2 or less toxicities not related to dosage included alopecia, anorexia, stomatitis, diarrhea, and epigastric pain. Dose limiting toxicities (DLT) as grade 4 leukopenia and grade 4 fatigue were seen at 80 mg/m2. The phase II dose was defined at 70 mg/m2 with rapidly reversible leukopenia and minor liver function abnormalities. At this dosing level, dose intensity was 88% and 86% over consecutive cycles for docetaxel and EP, respectively. Two vascular events occurred at this dose level (70 mg/m2): one arterial and the other venous. PSA decreases greater than 50% from baseline were seen in 14 of 17 patients at all dosage levels. Four of the 17 patients demonstrated a complete biochemical response (PSA < or = 4 ng/ml). One patient had a partial response with measurable lung and liver lesions.. EP given continuously with every three-week docetaxel at a dose of 70 mg/m2 is tolerable with evidence of antitumor activity based upon significant declines in PSA in the majority of patients and improvement of lung metastasis in one patient. Larger phase II studies of this combination in a homogenous population are warranted.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Estramustine; Humans; Lung Neoplasms; Male; Middle Aged; Paclitaxel; Prognosis; Prostatic Neoplasms; Survival Rate; Taxoids; Treatment Outcome

To evaluate the combination of intravenous (IV) paclitaxel, oral estramustine, and oral etoposide in patients with advanced hormone-refractory prostate cancer.. Forty patients with carcinoma of the prostate that was progressing despite hormonal therapy and who had undergone antiandrogen withdrawal (if previously treated with an antiandrogen) were enrolled onto this phase II trial. Patients were treated with oral estramustine 280 mg tid and oral etoposide 100 mg/d for 7 days, with paclitaxel 135 mg/m(2) IV over 1 hour on day 2 of each 21-day treatment cycle. Patients received a maximum of six cycles of therapy.. Thirty-seven patients were assessable for response. Twenty-two had measurable disease at baseline; response was not assessable in six of these patients. Overall response was 45% (10 of 22 patients; 95% confidence interval [CI], 24% to 68%), and response was 63% (10 of 16) in assessable patients. Twenty-six patients had a > or = 50% decrease from their baseline prostate-specific antigen levels during therapy, for a response rate of 65% (95% CI, 48% to 79%) by this criterion. Median duration of response was 3.2 months, with an estimated median survival of 12.8 months. Major toxicities of therapy were leukopenia (eight patients had > or = grade 4 leukopenia) and anemia. Hematologic toxicity seemed to be associated with liver metastases. Serial measurements in 24 patients using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) showed no significant change in quality of life (QOL) as a result of therapy.. The combination of IV paclitaxel, oral estramustine, and oral etoposide is active in patients with advanced prostate cancer. The regimen is tolerable and does not have a significant impact on QOL as measured by the FACT-P in a limited sample of patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Drug Resistance, Neoplasm; Estramustine; Etoposide; Humans; Male; Middle Aged; Paclitaxel; Prostatic Neoplasms; Quality of Life; Soft Tissue Neoplasms; Survival Rate; Treatment Outcome

Based on the theory that hormone-resistant cells are present in all metastatic patients, early administration of chemotherapy appears to be logical and its use is supported by experimental studies. Therefore, trials with combined hormonal and cytotoxic treatment as primary therapy should be conducted. In the present trial, the efficacy and tolerance of estramustine phosphate (EMP) as a chemotherapeutic agent in addition to hormonal treatment (orchiectomy) was studied in patients with metastatic and nonmetastatic prostate cancer not previously treated. EMP was chosen because it produces few serious adverse reactions and no cumulative toxicity.. Four hundred nineteen patients were included in a 1.5-year period starting in January 1989. Patients with locally advanced prostate cancer or with bone metastases were randomized to orchiectomy (O) or orchiectomy followed by EMP (O + E), given until progression.. Analysis of the total group showed no significant difference in time to progression between the treatment groups. Because the course of the disease is different in patients with either T4 tumor only or with lymph node metastases only (M0) as compared with patients with bone metastases (M1) and because the number of progressions in the M0 patients was low, corresponding analyses were performed for these subgroups as well. In the M1 patients, there was a tendency for a longer time to progression in the O + E group than in the O group, but there was no indication of a difference between the groups with regard to survival. In the M0 patients, there was no indication of any difference in results between the treatments. Multivariate analysis of prognostic factors showed pain, alkaline phosphatase, metastasis status, and tumor stage to be significant factors. There was a relation between age and drug treatment in that a significant beneficial effect of EMP in terms of prolonged progression-free interval as well as survival was evident in younger patients (aged less than 73 years) with metastatic disease. Tumor stage was also of importance for the drug effect; T0 to T3 patients who received EMP survived longer than those who were treated with orchiectomy only. The most common adverse reaction was nausea in the O + E group, which led to discontinuation of the drug in 7 patients. Cardiovascular problems are not uncommon in this age group, and there was a higher incidence of cardiovascular events, predominantly cardiac failure, in the O + E group, leading to treatment interruption in 16 patients.. Our results indicate that future studies of hormono/chemotherapy should focus on younger patients with bone metastases.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Combined Modality Therapy; Disease Progression; Estramustine; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostatic Neoplasms; Survival Rate

Hormone-refractory prostate cancer is characterized by a low response rate following second-line therapy. Encouraging results have been reported in Phase II studies with estramustine associated with vinblastine or etoposide. Vinorelbine is a new semisynthetic vinca alkaloid that has demonstrated activity in prostate cancer. We therefore evaluated the activity of the following schedule: estramustine, 400 mg/m2 orally days 1-42; etoposide, 50 mg/m2 orally days 1-14; and 28-42; vinorelbine, 20 mg/m2 days 1, 8, 28, and 35; cycles being repeated every 8 weeks. Twenty-five patients have been included and are assessable for response and side effects. Patient characteristics were as follows: median age, 71 years (range 55-81); ECOG performance status 0-2; nonosseous disease, 3 cases; bone metastases, 23 cases. Sixty-two cycles have been delivered. Two patients with measurable disease and six patients with bone disease had a partial remission for an overall response rate of 32% (95% confidence interval 15-53%). Seven patients had stabilization of disease and 10 had progression of disease. Median duration of response was 3 months (range 2-5). Prostate-specific antigen in 14 patients (56%) decreased from baseline by at least 50%. Toxicity was manageable. Neutropenia was mild, with only three cases of grade III-IV toxicity. Two patients had severe anemia. The results of this study indicate that the schedule is active and well tolerated in hormone-refractory prostate cancer patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Disease Progression; Drug Administration Schedule; Estramustine; Etoposide; Humans; Male; Middle Aged; Neutropenia; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Vinblastine; Vinorelbine

Two distinct regimens of weekly chemotherapy for hormone-refractory prostate cancer were combined in an alternating schedule and tested in a Phase II trial to determine efficacy and toxic effects. Forty-six patients with hormone-refractory prostate cancer and rising prostate-specific antigen (PSA) levels entered the trial. Therapy consisted of doxorubicin (20 mg/m2/week) plus oral ketoconazole (400 mg three times a day) given at weeks 1, 3, and 5 and vinblastine (5 mg/m2/week) plus oral estramustine (140 mg three times a day) given at weeks 2, 4, and 6. No therapy was given at weeks 7 and 8. Replacement doses of hydrocortisone were administered throughout treatment to counteract potential adrenal insufficiency secondary to the ketoconazole. In 67% of patients (31 of 46), the PSA declined by 50% or greater for a minimum duration of 8 weeks (95% confidence interval, 52-80%). Among the 16 patients with measurable soft tissue disease, there were 12 responses (75%; 95% confidence interval, 47-92%). The median duration of response was 8. 4 months (1.8-14.9). The median survival for the entire group was 19 months. The median survival of PSA responders has not been reached, whereas that of nonresponders was 13 months (P = 0.010). Seventy-six percent of symptomatic patients noted improvement. Hematological toxicity was modest and was managed without growth factors. Peripheral edema (49%) and deep venous thrombosis (18%) were the most common nonhematological toxicities. The alternating weekly regimen of chemohormonal therapy is active for hormone-refractory prostate cancer, providing a high rate of symptom control, soft tissue response, and PSA decline.

Topics: Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Bone and Bones; Bone Neoplasms; Combined Modality Therapy; Confidence Intervals; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Estramustine; Humans; Hydrocortisone; Ketoconazole; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Survival Analysis; Vinblastine

Estramustine phosphate is generally used as a second-line treatment in patients with advanced prostate cancer. The bone metastases due to the cancer are often treated simultaneously with clodronate in order to relieve the bone pain. Therefore, the interaction of clodronate (800 mg orally four times daily) and estramustine phosphate (280 mg orally twice daily) on their bioavailability was studied in twelve patients with prostate carcinoma and bone metastases. The drugs were first given separately, each to six patients, for five days, and then concomitantly for the same period. The bioavailabilities of the drugs were calculated on the last day of each treatment period. When clodronate was given alone, its concentrations in serum and AUC for one dose interval (6 hr) did not differ from those obtained with the drug given concomitantly with estramustine phosphate, nor did the combination of estramustine phosphate change the excretion of clodronate in urine. The serum concentrations of estramustine phosphate were elevated by about 80% when the drug was given together with clodronate. The AUC for one dose interval (12 hr) was also significantly higher for estramustine phosphate with clodronate than without clodronate. The urinary excretion of estrone, a major metabolite of estramustine phosphate, was also significantly higher after the admission with clodronate. The results suggest that clodronate increases the oral bioavailability of estramustine phosphate.

Topics: Administration, Oral; Aged; Aged, 80 and over; Analgesics, Non-Narcotic; Analysis of Variance; Antineoplastic Agents, Hormonal; Biological Availability; Bone Neoplasms; Carcinoma; Clodronic Acid; Drug Synergism; Drug Therapy, Combination; Estramustine; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Pain; Prostatic Neoplasms

Estramustine and etoposide (VP-16) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models. This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy.. Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d, were administered orally in divided doses for 21 days. Patients were then taken off therapy for 7 days and the cycle then repeated. Therapy continued until evidence of disease progression.. Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up. Of 18 patients with measurable soft tissue disease, three demonstrated a complete response (CR) and six a partial response (PR) for longer than 2 months. Of these 18 patients, pretreatment prostate-specific antigen (PSA) levels decreased by at least 75% in five men (28%) and by at least 50% in nine (50%). The median survival duration has not been reached in those patients who demonstrated a response either by soft tissue or PSA criteria. Of 24 patients with disease limited to bone, six (25%) demonstrated improvement and nine (38%) demonstrated stability in their bone scans. Five men (21%) demonstrated a decrease of at least 75% in pretreatment PSA levels and 14 (58%) demonstrated at least a 50% decrease; the median survival duration has not been reached in these patients. Pretreatment performance status is an important predictor of survival.. We conclude that the combination of estramustine and VP-16 is an active oral regimen in hormone-refractory prostate cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Estramustine; Etoposide; Follow-Up Studies; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Survival Rate

Clodronate relieves bone pain in patients with skeletal metastases. Since the pain relieving mechanism of clodronate may be associated with the antiosteoclastic activity, we have investigated whether the drug has simultaneous actions on bone resorption and pain. Although osteosclerotic metastases are characteristic of prostate carcinoma, bone resorption is also accelerated. The resorbing process can be investigated using a specific immunoassay for ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) which allows the measurement of the degradation of type I collagen in serum samples. We have also determined serum concentration of PICP (carboxyterminal propeptide of type I procollagen) which reflects the synthesis of type I collagen (osteoid). Patients who have relapsed after first-line hormonal therapy, were randomised to receive estramustine phosphate (E) with or without clodronate (C) (E + C, n = 50; E, n = 49). The dose of E was 560 mg and that of C 3.2 g for the first month, thereafter 1.6 g. We saw elevated ICTP and PICP levels in the majority of the patients. A transient decrease in ICTP values occurred simultaneously with pain relief. The changes were more accentuated in the E + C than in the E group but the difference was not significant. In each group serum phosphate concentration decreased markedly (P = 0.001) whereas the activity of alkaline phosphatase remained increased, both indicating a development of osteomalacia during E therapy. The short-term antiosteoclastic effect of C may be explained by the dose reduction, hyperosteoidosis and osteomalacia which inhibit the binding of C on the crystal surfaces and by the late phase of disease.

Topics: Administration, Oral; Aged; Aged, 80 and over; Bone Neoplasms; Bone Resorption; Clodronic Acid; Collagen; Estramustine; Humans; Male; Middle Aged; Pain; Palliative Care; Peptide Fragments; Procollagen; Prostatic Neoplasms

Forty-three patients with disseminated prostate cancer, resistant to orchidectomy or hormone therapy with estramustine were treated. Of the 33 evaluable patients, three patients had stable disease and two had a partial tumour response according to National Prostatic Cancer Project criteria. Twenty-five patients (58%) showed improvement in pain and urinary symptoms. Ten patients (23%) had side effects requiring cessation of therapy. These results show that estramustine has a limited role in the treatment of advanced prostate cancer and that therapy is frequently associated with intolerable side effects.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Neoplasms; Cohort Studies; Disease-Free Survival; Estramustine; Humans; Male; Middle Aged; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Treatment Outcome

Although osteosclerotic metastases are characteristic of prostatic carcinoma, bone resorption is also accelerated. Since clodronate inhibits bone resorption and relieves bone pain, we have given it to patients with painful bone disease from prostatic cancer after failure of hormonal therapy. All patients received estramustine phosphate orally. Simultaneously they were randomly allocated to clodronate (36) and placebo (39) groups. Clodronate was given by mouth. The dose was 3.2 g for the first month, thereafter 1.6 g. Pain relief was more distinct in the clodronate group where one third of patients were totally free of bone pain. The use of analgesics stopped in 38% of patients on clodronate and in 18% on placebo which effect probably belongs to estramustine phosphate. Serum calcium concentration decreased more markedly in the clodronate group. Clodronate dose of 3.2 g seemed to be more potent than that of 1.6 g. Side effects were uncommon and occurred equally in both groups. No significant differences were seen in median survival or survival rates between the groups.

Topics: Administration, Oral; Aged; Analgesics; Bone Neoplasms; Calcium; Clodronic Acid; Estramustine; Humans; Male; Pain; Prostatic Neoplasms

A series of 105 patients with metastatic prostatic cancer, having progressed on first-line hormonal treatment, were randomised to high-dose medroxyprogesterone acetate (MPA) 1000 mg i.m. daily for 15 days, followed by 1000 mg weekly (53 patients), or to estramustine 280 mg per os twice daily (52 patients). The treatment was discontinued because of side effects in 3 of 51 evaluable MPA-treated patients and in 8 of 51 evaluable estramustine-treated patients. Progression-free survival was short in both groups and no statistically significant difference between them was observed. After 1 year, 70% of the patients had died and there was no statistically significant difference between the 2 treatments in the cumulative observed survival rates. According to modified SPCG criteria, remissions lasting from 12 to 56 weeks were noted in 13 MPA-treated patients and in 4 estramustine-treated patients. This difference was statistically significant. After cross-over, 6 of 33 patients in the MPA group had a remission compared with 1 of 24 in the estramustine group. It was concluded that the response rate, considering both subjective and objective response criteria, was better with MPA and the side effects were fewer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Delayed-Action Preparations; Estramustine; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Prognosis; Prostatic Neoplasms; Time Factors

Thirty patients with metastatic cancers but with no serious cardiovascular (CV) conditions were randomly assigned to receive treatment either with flutamide (250 mg x 3) (F) or with estramustine (280 mg x 2) (E). Clinical examination, bone scan, laboratory measurements were performed before randomization and at regular intervals thereafter. During an observation period of between 1 and 2.5 years, F was discontinued in one case (7%) because of icterus, and E in three cases (20%) because of CV complications. Of the remaining 14 F-treated patients, 13 responded initially. Eleven of them relapsed, and five died of cancer. In the corresponding group of 12 E-treated patients, there were 11 primary responders. Of these, only two relapsed and died, as did the only nonresponder. The difference between the two groups with regard to relapse is significant (p less than 0.01), but not with regard to mortality. In the present material, there was an initial favorable response to F without signs of CV complications and with maintained libido in most cases. However, due to the significantly increased risk for relapse compared with E, F cannot be recommended as single therapy except in cases where estrogens are contraindicated or when interference with libido and potency is unacceptable.

Topics: Adenocarcinoma; Aged; Anilides; Bone Neoplasms; Estramustine; Flutamide; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Nitrogen Mustard Compounds; Prospective Studies; Prostatic Neoplasms; Random Allocation; Time Factors

The efficacy and side effects of flutamide were compared with estramustine in patients with advanced prostatic carcinoma. Thirty patients with metastatic cancers but with no serious cardiovascular (CV) conditions were randomly assigned to receive treatment either with flutamide (250 mg X 3) or with estramustine (280 mg X 2). Clinical examination, bone scan, laboratory measurements, including coagulation studies were performed prior to randomization, every three months during year one, and at six-month intervals thereafter. The two groups were comparable with respect to age and tumor characteristics. However, more patients presented with skeletal pain among those later treated with flutamide. During an observation period of between one and two and one-half years, flutamide was discontinued in 1 case (7%) because of icterus, and estramustine in 3 cases (20%) because of CV complications. Of the remaining 14 flutamide-treated patients, 13 responded initially. Eleven of them relapsed, and 5 died of cancer. In the corresponding group of 12 estramustine-treated patients, there were 11 primary responders. Of these, only 2 relapsed and died as did the only nonresponder. The difference between the two groups with regard to relapse is significant (P less than 0.01), but not with regard to mortality. All estramustine-treated patients lost their libido, whereas only 20 per cent of the patients treated with flutamide did so. In the present limited material there was an initial favorable response to flutamide without signs of CV complications and with maintained libido in most cases. However, due to significantly increased risk for relapse compared with estramustine, flutamide cannot be recommended as single therapy except in cases where estrogens are contraindicated or when interference with libido and potency is unacceptable.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anilides; Bone Neoplasms; Estramustine; Flutamide; Humans; Libido; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation; Time Factors

In a randomized phase III trial performed by the Urological Group of the European Organization for Research on Treatment of Cancer low dose estramustine phosphate (280 mg. twice daily for 8 weeks and 140 mg. twice daily thereafter) was compared to diethylstilbestrol (1 mg. 3 times daily) in patients with stages T3 to T4, M0 or M1 prostatic cancer. Of 248 patients entered 227 were evaluable for analysis: 115 received estramustine phosphate and 112 received diethylstilbestrol. The best response of the local tumor as assessed by palpation was seen in patients receiving diethylstilbestrol. There was no significant difference between treatments for response rate of metastases, interval to local progression, distant progression, over-all survival and death of carcinoma of the prostate. Duration of survival was correlated with the assessment of local response as determined by palpation. The response of distant lesions also was correlated closely with survival. Diethylstilbestrol (1 mg. 3 times daily) was associated with a significantly worse degree of cardiovascular toxicity than estramustine phosphate. This finding was especially obvious in patients who had no history of cardiovascular disease. Gastrointestinal toxicity occurred in 25 patients treated with estramustine phosphate, including 6 in whom cessation of treatment was necessary. Further studies are required to determine the optimum dose of diethylstilbestrol and estramustine phosphate, and to establish the best form of hormonal treatment for prostatic carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma; Cardiovascular Diseases; Clinical Trials as Topic; Diethylstilbestrol; Estramustine; Europe; Gastrointestinal Diseases; Humans; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation

Serial transrectal needle biopsies were taken from 146 patients (657 specimens) with advanced prostatic cancer (T3/T4, M1/MO) admitted to a trial of two forms of oestrogen therapy. Histological grading by Gleason and Mostofi techniques on the initial biopsy showed no correlation either with extent of disease or its eventual outcome on treatment. Change in grade was dissociated from the response of bone metastases to hormone treatment and did not appear to influence survival. However, the prognosis of 16 patients showing clearance of tumour from their serial biopsies was generally good.

Topics: Aged; Bone Neoplasms; Clinical Trials as Topic; Diethylstilbestrol; Estramustine; Humans; Male; Middle Aged; Prognosis; Prostate; Prostatic Neoplasms; Time Factors

Topics: Bone Neoplasms; Clinical Trials as Topic; Diethylstilbestrol; Estramustine; Humans; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation; Time Factors; Wisconsin

In a prospective randomized multicenter trial patients with highly or moderately differentiated prostatic carcinoma, previously untreated, were allotted either to oral Estramustine phosphate or to intramuscular polyestradiol phosphate plus oral ethinyl estradiol. As regards frequency and duration of tumour remission there was no statistical difference between the two groups. Nor did they differ significantly with respect to adverse reactions. This is an interim report and will be followed later on by a final evaluation.

Topics: Bone Neoplasms; Estramustine; Estrogens; Humans; Male; Neoplasm Staging; Nitrogen Mustard Compounds; Phosphoric Monoester Hydrolases; Prostatic Neoplasms; Random Allocation

A 66-year-old man was referred to our outpatient clinic for an elevated serum prostatic-specific antigen (PSA 4,319 ng/ mL). Magnetic resonance imaging (MRI) showed multiple metastatic lesions in the bones. The patient had received androgen deprivation therapy, but six months after treatment, he was diagnosed as having prostate cancer refractory to hormones. Combined treatment with docetaxel (DOC 30 mg/m²/week )and estramustine phosphate (EMP 560 mg/day) was initiated as first-line chemotherapy, but the treatment was discontinued because of side effects. Then, treatment with zoledronic acid was started(4 mg/4 weeks)and the PSA level decreased dramatically from 457.2 ng/mL to 5.5 ng/mL. Seven months after the diagnosis of CRPC, MRI showed a decrease ofbone metastases, and the PSA levels continued to decrease, eventually reaching 0.3 ng/mL. Zoledronic acid appears to not only show efficacy in preventing skeletal-related events, but has a potential antitumor effect in patients with metastatic CRPC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Castration; Diphosphonates; Estramustine; Fatal Outcome; Humans; Imidazoles; Magnetic Resonance Imaging; Male; Prednisolone; Prostate-Specific Antigen; Prostatic Neoplasms; Zoledronic Acid

Metastatic prostate cancer (PC) is incurable by androgen deprivation therapy alone, due to the presence of androgen-independent/supersensitive cells in hormone-naive PC. A 67-year-old man was diagnosed with PC (Gleason score, 5 + 4) with multiple bone metastases. He was treated by chemohormonal therapy with cisplatin and estramustine phosphate (EMP) followed by maximal androgen blockade, and showed a complete response. As of the time of writing, no clinical or prostate-specific antigen recurrence has been observed for over 15 years, despite cessation of the treatment. This is the first report to indicate a possible cure of metastatic PC by chemohormonal therapy combined with appropriate anti-tumor drugs targeted to both androgen-independent and -dependent clones before the hormone-refractory state.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Estramustine; Humans; Male; Prostatic Neoplasms

Chemotherapy has emerged as a standard treatment in patients with castration-refractory prostate cancer (CRPC). Consensus criteria are available to define response in CRPC as at least a 50% decline in serum prostate-specific antigen (PSA) confirmed 4 weeks later. The objective of this work was to study early serum PSA changes in patients under chemotherapy and to correlate these changes with subsequent response assessment.. Serum PSA levels were monitored every 3 weeks in 79 patients with CRPC treated with chemotherapy and a time course of serum PSA levels was obtained. Correlation with response was studied.. According to consensus criteria, 21 (40%) and 20 (38%) patients achieved a PSA response and stabilization, respectively, after first-line chemotherapy. Among patients who achieved either a response or a stabilization, 8 of 41 (20%) had a serum PSA rise during the first 8 weeks of chemotherapy, followed by a subsequent decline in serum PSA. The same observation was made in patients receiving second-line chemotherapy: 6 of 20 patients achieving a response or stabilization had an initial serum PSA rise. The postchemotherapy increase in serum PSA could reach more than twice the baseline value. The duration of the PSA surge ranged from 1 to 8 weeks. When considering responders only, 6 of 30 (20%) had a postchemotherapy serum PSA surge, followed by a drop.. Postchemotherapy PSA surges occur not infrequently in patients with CRPC who respond to chemotherapy. Physicians should be aware of this effect to avoid inadequate early discontinuation of chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Docetaxel; Estramustine; Gonadotropin-Releasing Hormone; Humans; Kinetics; Male; Middle Aged; Mitoxantrone; Neoplasm Metastasis; Orchiectomy; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms; Sesquiterpenes; Syndrome; Taxoids; Treatment Outcome

This case report demonstrates the effect of zoledronic acid (ZA) on a patient with bone metastatic hormone-refractory prostate cancer (HRPC) resistant to taxane, estramustine phosphate, carboplatin, and dexamethasone. The pathogenesis, diagnosis, and management of bone metastasis on HRPC are also reviewed.

Topics: Aged; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Bone Neoplasms; Bridged-Ring Compounds; Carboplatin; Dexamethasone; Diphosphonates; Drug Resistance, Neoplasm; Estramustine; Humans; Imidazoles; Male; Prostatic Neoplasms; Taxoids; Zoledronic Acid

Topics: Antineoplastic Agents; Bone Neoplasms; Carboplatin; Diphosphonates; Docetaxel; Estramustine; Humans; Imidazoles; Male; Prostatic Neoplasms; Taxoids; Zoledronic Acid

To assess the clinical pattern of progression and prostate-specific antigen doubling time (PSA-DT) after exposure to docetaxel-based chemotherapy in patients with androgen-independent prostate cancer (AIPC).. Fifty-five patients received docetaxel-based chemotherapy; data were collected retrospectively from three different departments. Progression was known in 44 (79%) and the PSA-DT was available in 33 patients.. Of the 29 patients with soft-tissue and soft-tissue plus bone metastases, 22 (76%) developed soft-tissue progression. Among the 35 patients with bone and bone plus soft-tissue metastases, 27 (77%) had osseous progression. There was no difference between the PSA-DT at progression before and after docetaxel-based therapy (mean 3.1 vs 2.7 months, P = 0.592, Student's t-test.). However, the median (range) PSA-DT at progression after docetaxel-based therapy was 0.84 (0.3-4) months in patients with a PSA response, significantly shorter than the median of 3.1 (0.3-12) months of patients with no biochemical response (P = 0.002, Student's t-test). The PSA-DT dynamics at progression had no effect on survival (P = 0.63, log-rank test).. The pattern of progression after docetaxel-based chemotherapy is predominantly osseous in patient with bone metastases and mostly soft-tissue in those with soft-tissue disease. Progression after docetaxel-based chemotherapy in AIPC does not modify the PSA-DT before docetaxel. Evaluation of a larger population is needed to assess the clinical relevance of PSA dynamics after docetaxel therapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Disease Progression; Docetaxel; Estramustine; Humans; Male; Middle Aged; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Soft Tissue Neoplasms; Survival Analysis; Taxoids; Treatment Outcome

Prostate carcinoma is one of the most frecuent cancers in men. Significant numbers of patients have regional lymph node and bone metastases during the course of the disease. Mediastinal lymphadenopathy and cutaneous metastases are uncommon and signify well-advanced disease. We report the case of a patient with prostate cancer who develops mediastinal lymphadenopathy, pulmonary nodules and cutaneous metastases 8 years after the diagnosis.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyproterone; Diphosphonates; Estramustine; Fatal Outcome; Flutamide; Humans; Imidazoles; Ketoconazole; Lung Neoplasms; Lymphatic Metastasis; Male; Mediastinum; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Radionuclide Imaging; Skin Neoplasms; Triptorelin Pamoate; Zoledronic Acid

The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases.

Topics: Activities of Daily Living; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Combined Modality Therapy; Diphosphonates; Estramustine; Humans; Male; Prostatic Neoplasms; Quality of Life; Radiography; Radionuclide Imaging

Docetaxel is an effective agent for the treatment of androgen-independent prostate cancer (AIPC). Its combination with estramustine phosphate (EMP) has shown promising results in AIPC but the toxicity remains considerable. In an effort to minimize toxicity, we designed an every-2-week docetaxel administration regimen with a 3-day low-dose EMP regimen. Patients with bone metastases also received zoledronic acid.. A total of 54 patients with AIPC received docetaxel at 45 mg/m2 and EMP (140 mg orally every 8 hours for nine doses) every 2 weeks. Zoledronic acid was administered at 4 mg every 28 days.. Of the 49 assessable patients, 22 (45%, 95% confidence interval [CI] 31% to 60%) had a prostate-specific antigen response. Of 24 patients with measurable disease, 9 (38%, 95% CI 19% to 59%) had a response to therapy (one complete response and eight partial responses). The median time to progression was 4.4 months (95% CI 2.7 to 6), and overall survival was 13.3 months (95% CI 9 to 17.6). Toxicity was mild, with only 5 cases of grade 3 or 4 toxicity. The pain score improved by 1 point in 21 (54%) of 39 symptomatic patients, and 14 (40%) of 38 patients who used analgesics discontinued analgesic consumption by the end of treatment.. The combination of an every-2-week regimen of docetaxel, EMP, and zoledronic acid is an effective, well-tolerated regimen that results in symptomatic improvement in a significant proportion of patients with AIPC.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alopecia; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Diphosphonates; Disease Progression; Disease-Free Survival; Docetaxel; Drug Resistance, Neoplasm; Estramustine; Humans; Imidazoles; Life Tables; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Proteins; Neutropenia; Orchiectomy; Pain; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, High-Energy; Remission Induction; Survival Analysis; Taxoids; Treatment Outcome; Zoledronic Acid

Although treatment of hormone-refractory prostate cancer (HRPC) is difficult, a single-agent weekly dose of docetaxel has been reported as a promising regimen for patients with HRPC. The purpose of this study was the investigation of the efficacy of docetaxel for Japanese patients with HRPC.. Ten patients with HRPC were treated with weekly docetaxel at Tsukuba University Hospital and were evaluated for the responses with respect to serum prostate-specific antigen (PSA), tumor size and survival. Considering the ethnic balance, the dose of docetaxel was reduced to 30 mg/m(2) weekly compared with 36 mg/m(2) in the study reported previously.. A biochemical response (>50% decrease in PSA) was observed in five patients (56%; 5/9) with an average time to progression of 4.5 months. In two partial responders as determined by PSA, respective metastatic lesions in bone and soft tissue were also improved. The estimated median survival duration was 6 months. Most of these responses were accompanied by a significant reduction in the requirement for analgesic agents. No severe toxicity of this regimen was observed, except for gastric ulcer in one patient who was excluded from the evaluation.. Weekly administration of docetaxel as a single agent was associated with a high rate of PSA reduction. This treatment is feasible for patients with HRPC, even those who have a poor performance status and extensive prior treatments.

Topics: Aged; Alopecia; Anorexia; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Bone Neoplasms; Docetaxel; Drug Administration Schedule; Drug Resistance, Neoplasm; Estramustine; Feasibility Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Soft Tissue Neoplasms; Taxoids

We report on a patient with androgen ablation-refractory prostate adenocarcinoma who had an objective response for longer than 24 months using a combination of estramustine and lanreotide. At baseline from our combination therapy, his prostate-specific antigen level was 21.30 ng/mL and serum chromogranin A level was 816 ng/mL. The patient discontinued complete androgen deprivation therapy and underwent combination therapy with oral estramustine 420 mg/day plus lanreotide acetate 73.9 mg intramuscularly every 4 weeks. After 33 months of follow-up, the patient was alive without clinical disease progression, and his prostate-specific antigen and chromogranin A level was 0.10 and 12 ng/mL, respectively.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chromogranin A; Chromogranins; Estramustine; Humans; Male; Peptides, Cyclic; Prostate-Specific Antigen; Prostatic Neoplasms; Somatostatin

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Bone Neoplasms; Diphosphonates; Drug Resistance, Neoplasm; Drug Therapy, Combination; Estramustine; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

We describe a patient with androgen-independent prostate cancer in whom hypocalcemia developed during treatment with estramustine. The patient's total serum calcium level before and after the initiation of estramustine was 8.3 and 4.3 mg/dL, respectively (normal range 8.4 to 10.2). This finding prompted us to review the calcium levels in 135 consecutive patients who were also undergoing treatment with a similar estramustine-containing regimen. We found that hypocalcemia had developed in 20% of these patients during treatment. We speculate that estramustine may cause hypocalcemia by inhibiting the mobilization of calcium and the action of the parathyroid hormone in the skeleton.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Bone Neoplasms; Estramustine; Humans; Hypocalcemia; Incidence; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

Clinical effects of estramustine phosphate (EMT) on hormone refractory prostate cancer were studied. Prostate cancer relapsed in 70 of the 259 patients with stage C and D diseases who had initially responded to endocrine therapy. After cancer relapse, endocrine therapy was changed to oral administration of EMT in 21 patients, while initial endocrine therapy was continued in 14 and additional radiation therapy was given in 35. A partial response or no change was observed in 11 of the 21 patients (52%) given EMT therapy, the mean duration of the response being 14.2 months. The 21 patients given EMT therapy survived significantly longer than the 14 patients with continued on endocrine therapy, and those responding to EMT therapy tended to have a better survival than those unresponsive. Side effects of EMT included loss of appetite in 2 patients and edema of the lower limb in 1, but they were not severe enough to require discontinuation of the drug. EMT may be a useful drug for patients with advanced prostate cancer with relapse after endocrine therapy.

Topics: Administration, Oral; Aged; Antineoplastic Agents, Hormonal; Bone Neoplasms; Drug Resistance, Neoplasm; Estramustine; Humans; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; Survival Rate

Procollagen 1 carboxyterminal peptide (P1CP) is thought to be an indicator of new bone formation. The present report demonstrates that effective endocrine therapy induced an initial increase followed by a delayed decrease in serum levels of P1CP and alkaline phosphatase in spite of an immediate decrease in serum PSA and PAP and improvement of clinical symptoms in prostate cancer patients with bone metastases. The transient increase in P1CP and alkaline phosphatase is a healing reaction and is followed by apparent improvement. Short-term effects of endocrine therapy on prostate cancer patients with bone metastases should be comprehensively evaluated based upon the entire spectrum of clinical and laboratory findings including serial changes of serum prostate markers and bone markers as well.

Topics: Adenocarcinoma; Aged; Alkaline Phosphatase; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Diethylstilbestrol; Estramustine; Gonadotropin-Releasing Hormone; Humans; Male; Peptide Fragments; Procollagen; Prostatic Neoplasms

The time from first diagnosis of primary multiple metastatic prostate carcinoma until progression and until death in patients less than 60 years old under two different therapeutic regimens was evaluated.. In the group with pure androgen deprivation (n = 21), the mean time until progression was 11.3 (6-55) months, the mean survival time being 21.4 (11-75) months. In the group with androgen deprivation plus cytostatic therapy (n = 10), progression was noted after 26.7 (15-77) months with a medium survival time of 26.2 (16-82) months.. The data argue in favor of changing the usual treatment strategy to combination therapy in "young' patients with primary metastatic prostatic cancer.

Topics: Adult; Androgens; Antineoplastic Agents; Bone Neoplasms; Carcinoma; Castration; Cisplatin; Combined Modality Therapy; Doxorubicin; Estramustine; Gonadotropin-Releasing Hormone; Guidelines as Topic; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; World Health Organization

We evaluated the effectiveness of combination chemotherapy using estramustine and velban for metastatic prostate cancer. Patients with progressive metasatatic prostate cancer and rising prostate-specific antigen (PSA) values were evaluated between 1992 and 1994. All treatment was given on an outpatient basis. Vinblastine, 4 mg/m2 i.v., was given weekly for 6 weeks with a 2-week rest period. Estramustine, 10 mg/kg orally, was given in three divided doses for 6 weeks with a 2-week rest period between cycles. Of 15 patients, six (40%) had a response, in which a 25% decrease in PSA was associated with subjective improvement. There were no complete responses. Five partial responders had less pain. Median duration of response or time to progression was 9 months. Survival was 11.7 months for responders, 13.2 months for nonresponders. The combination of estramustine and velban is an effective therapy in progressive metastatic prostate cancer as measured by a decrease in PSA and improvement of symptoms.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Disease Progression; Drug Administration Schedule; Estramustine; Humans; Lymphatic Metastasis; Male; Middle Aged; Pain; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Survival Rate; Vinblastine

An 89-year-old man with bilateral leg edema and a huge abdominal mass was admitted for further evaluation. CT scan showed a hugh prostatic mass which occupied the whole pelvis cavity accompanying multiple pelvic bone metastases. Suprapubic needle biopsy revealed that the mass was well differentiated adenocarcinoma of prostate origin. The treatment was initiated by 500 mg per day of estramustine phosphate combined with injectable LH-RH analogue 2 months later. The serum levels of tumor markers were markedly elevated at the first visit; PSA 210ng/ml, PAP 110ng/ml, gamma-Sm 800ng/ml. They became normalized 3 months after the initiation of the treatment, and the mass was reduced to 11.5% of the initial size, which lead to removal of indwelling urethral catheter. The patient and his family, however, refused further treatment and the patient died of disseminated disease 8 months later.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Neoplasms; Estramustine; Humans; Leuprolide; Male; Prostatic Neoplasms

We report a case of advanced prostate cancer in which an initial response to hormonal therapy with surgical castration and estramustine phosphate (EMP) was followed by disease progression, as shown by sequential elevations in serum prostate specific antigen (PSA) and prostate acid phosphatase (PAP) and the development of new symptoms, during maintenance endocrine and anti-cancer chemotherapy. Discontinuation of EMP resulted in sustained reductions in serum PSA and PAP levels and a sustained improvement in symptoms.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Bone Neoplasms; Castration; Estramustine; Humans; Lung Neoplasms; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

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

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Carcinoma; Chlormadinone Acetate; Diagnosis, Differential; Estramustine; False Positive Reactions; Follow-Up Studies; Humans; Male; Middle Aged; Osteolysis; Prostatic Neoplasms; Radionuclide Imaging; Spinal Diseases; Spinal Neoplasms; Tomography, X-Ray Computed

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

Topics: Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Cyclophosphamide; Estramustine; Estrogens; Flutamide; Follow-Up Studies; Humans; Male; Neoplasm Proteins; Neoplasm Staging; Orchiectomy; Predictive Value of Tests; Prostatic Neoplasms; Treatment Outcome

A 55-year-old man consulted us on December 3, 1986 with the chief complaints of left leg pain, disturbance in gait and dysuria. On digital rectal examination his prostate was found enlarged to a hen's egg size and increased in consistency. He was admitted to the hospital under the suspicion of prostatic cancer on December 8, 1986. Scout kidney-ureter-bladder X-ray revealed extensive osteolytic lesions in the left iliac and pubic bones as well as in the sacrum. Needle biopsy of the prostate demonstrated moderately differentiated adenocarcinoma, leading to a diagnosis of prostatic cancer with osteolytic bone metastases. Bone scintigraphy showed increased radioactivity uptake by the left iliac and pubic bones. Pelvic CT disclosed large tumor masses in the left ilium and sacrum, which on bone biopsy were identified as poorly differentiated adenocarcinoma. Endocrine therapy with estramustinphosphate and castration was performed along with transurethral resection of prostate. At week 16 after initiating the therapeutic regimen the patient was entirely free from disturbance in gait and the tumor mass of the left iliac bone had disappeared almost completely on the computed tomogram at week 18, although osteolytic lesions still persisted on the x-ray. This case deserves special note because endocrine therapy markedly reduced the size of the bone tumors, in spite of osteolytic bone metastases of prostatic cancer with computed tomographic evidence of large metastatic tumor masses.

Topics: Adenocarcinoma; Adult; Bone Neoplasms; Castration; Estramustine; Humans; Male; Osteolysis; Prostatic Neoplasms; Tomography, X-Ray Computed

One hundred and twenty-seven patients with locally advanced prostatic cancer were evaluated for the presence and progress of bone metastases before and during hormonal therapy, by serial radionuclide imaging and frequent measurement of plasma acid (tartrate-labile) and alkaline phosphatase. For comparison, serial changes in imaging and phosphatases were classified in each patient into one of six groups. Of 71 patients with negative imaging before treatment, 82% had normal alkaline phosphatase levels and 83% had normal acid phosphatase levels. Of 56 patients with bone metastases at presentation, false negative alkaline and acid phosphatase levels were noted in 18% and 36% respectively, though a few patients eventually developed abnormal levels. Serial plasma biochemistry and particularly alkaline phosphatase showed a response to treatment which was not always obvious on imaging. An assessment of the hepatic component of alkaline phosphatase by reference to plasma gamma glutamyl transpeptidase and isoenzyme electrophoresis was helpful in the evaluation of a false positive result but unnecessary where imaging was positive and phosphatase elevated. It is concluded that serial alkaline phosphatase estimation is essential in the follow-up of patients with prostatic cancer and bone metastases, and probably renders serial imaging studies superfluous once the presence of skeletal metastases has been proven. By comparison, acid phosphatase is a much less effective marker.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Diethylstilbestrol; Estramustine; Follow-Up Studies; Humans; Male; Middle Aged; Prostatic Neoplasms; Radionuclide Imaging

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Castration; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Estramustine; Fluorouracil; Humans; Male; Middle Aged; Postoperative Care; Prostatic Neoplasms

This report is an evaluation of the changes in bone scans in certain patients entered into the EORTC protocol 30762 and discusses the relevance of these expensive investigations.

Topics: Bone Neoplasms; Diethylstilbestrol; Estramustine; Humans; Male; Prognosis; Prostatic Neoplasms; Radionuclide Imaging

Estramustine phosphate ( Estracyt ) was used in 32 patients with a mean age of 73 and a half years suffering from oestrogen-resistant carcinoma of the prostate. These carcinomas were advanced and were divided into 26 stage D and 6 stage C. Treatment was given orally at a dose of 600 mg per day. Results were assessed on the basis of reliable subjective and objective selected criteria. Objective responses were obtained in 28,1% of cases and subjective responses in 40.6%. All the patients in whom there was an objective response showed a subjective response. Objective action was more marked on the primary tumour than on metastases. There was a decrease in bone pain, an improvement in general condition and disappearance of dysuria in more than a third of all cases. When there was a response, it always occurred before the end of the 2nd month and was maximal at 3 months. The mean duration of a response was 29.1 months for objective responses and 27.7 months for subjective responses. Survival of patients responding to treatment was markedly longer (by 15 months on average) than in patients who failed to respond. The low level of toxicity of the compound, even after prolonged use, makes its use possible in all patients. Thus Estracyt is felt to have a role in the treatment of the severe forms represented by hormone-resistant carcinomas of the prostate.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Drug Resistance; Estramustine; Estrogens; Follow-Up Studies; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Time Factors

Topics: Aged; Bone Neoplasms; Drug Resistance; Estramustine; Estrogens; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms

Topics: Bone Neoplasms; Estramustine; Female; Humans; Male; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prostatic Neoplasms

The low incidence of measurable or evaluable metastases in patients with prostatic cancer makes evaluation of response difficult. This is particularly true in patients with bone metastases only. With a digital model it is possible to measure quantitatively from the radioisotope bone scan the total area of skeletal involvement by metastatic tumor. Definitions of response in bone have been derived from this model. These response criteria have been compared to response in acid phosphatase determinations and clinical status in a study of 44 patients with advanced prostatic cancer treated with estramustine phosphate. Based on serial quantitative bone scans, serial measurements of acid phosphatase levels and repeat clinical evaluations a system is proposed for defining response to systemic therapy that is applicable to the majority of patients with metastatic prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Bone Neoplasms; Diphosphates; Diphosphonates; Estramustine; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Radionuclide Imaging; Technetium

Ninety patients with poorly differentiated prostatic carcinoma have been treated with Estramustine phosphate (Estracyt). Seventeen of them had clinically metastases and had had no previous therapy. Seventy-three were initially given oestrogens and/or irradiation. Objective response was observed in 59%. The best effect was seen in patients primarily untreated.

Topics: Acid Phosphatase; Bone Neoplasms; Estramustine; Humans; Lymphatic Metastasis; Male; Neoplasm Metastasis; Nitrogen Mustard Compounds; Pain; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Estramustine; Humans; Male; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prostatic Neoplasms; Radiography; Remission, Spontaneous

40 patients with prostatic carcinoma were treated with parenteral and/or oral Estracyt (estramustine phosphate) until 55 months. Metastases were present in 37 patients (stage D). 35 of the 40 patients developed metastases in spite of estrogen therapy and/or orchidectomy. Diminution of metastasic bone pain as well as improvement of hydroureteronephrosis was frequently observed. Paraplegia secondary to metastatic disease improved in 1 case for 6 months. Side effects were relatively rare and were mainly gastrointestinal. A possible hepatotoxic action of the compound has been pointed out previously. On the basis of our studies Estracyt is recommended in the treatment of primary estrogen resistent prostatic carcinoma and in metastatic carcinoma of the prostate not responding to conventional antiandrogenic therapy anymore.

Topics: Administration, Oral; Aged; Bone Neoplasms; Carcinoma; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemistry; Estramustine; Estrogens; Humans; Injections, Intravenous; Long-Term Care; Male; Middle Aged; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prostatic Neoplasms