Evaluation of docetaxel plus estramustine in the treatment of patients with hormone-refractory prostate cancer

Objectives:   To investigate the feasibility and efficacy of docetaxel-based chemotherapy in patients with hormone-refractory prostate cancer (HRPC).
Methods:   Forty-six consecutive HRPC patients treated between January 2003 and March 2008 were included in this analysis. Docetaxel was given at a dose of 35 mg/m² twice every 3 weeks and oral estramustine concurrently for three consecutive days during weeks 1 and 2 of each cycle. During each treatment week, the dose of estramustine was 1260 mg on the first day, 980 mg on the second day and 840 mg on the third day. Patients were premedicated with 4 mg twice a day of oral dexamethasone for three consecutive days. Treatment was continued until evidence of disease progression or unacceptable toxicity. Prostate-specific antigen (PSA) levels were evaluated at least once every 4 weeks.
Results:   Patients received a median of three cycles of chemotherapy. Of the evaluable 46 patients, 25 (54%) had a ≥50% PSA decline and 12 (26%) had a ≥75% PSA decline. Median time to PSA progression and overall survival time were 10.1 and 27.0 months, respectively. Median follow-up was 15.0 months. Major severe toxicities were grade 3 or 4 leukopenia in five (11%) patients. Mild toxicities included grade 1 or 2 nausea in eight (17%) patients. Two patients could not continue the treatment because of interstitial pneumonitis and a gastric hemorrhage, respectively.
Conclusions:   Docetaxel plus estramustine chemotherapy represents an active and well tolerated treatment for Japanese HRPC patients.     

Chemohormonal therapy as primary treatment for metastatic prostate cancer: A randomized study of estramustine phosphate plus luteinizing hormone-releasing hormone agonist versus flutamide plus luteinizing hormone-releasing hormone agonist

BACKGROUND: The present study was undertaken mainly to investigate whether chemohormonal therapy with estramustine phosphate plus luteinizing hormone-releasing hormone (LHRH) agonist has a more beneficial effect than the hormonal therapy with flutamide plus LHRH agonist for newly diagnosed patients with metastatic prostate cancer. METHODS: A total of 57 patients with metastatic prostate cancer aged 59-80 years (median 74 years) were entered in the study and were randomized to the treatment of estramustine phosphate (560 mg/day) plus LHRH agonist (estramustine group) or flutamide (375 mg/day) plus LHRH agonist (flutamide group) with stratification for the degree of performance status, histological differentiation and bone metastasis. RESULTS: Both of the treatment regimens were well tolerated with similar incidences of adverse drug reactions. The overall response rates (complete response plus partial response) at 12 weeks after treatment in the estramustine and flutamide groups were 76 and 55%, respectively. The median time to objective progression for the estramustine group (25.4 months) was longer than that of the flutamide group (14.6 months). The serum levels of follicle stimulating hormone and testosterone were significantly lower in the estramustine group. CONCLUSIONS: Chemohormonal therapy with estramustine phosphate plus LHRH agonist showed longer clinical progression-free survival than the hormonal therapy with flutamide plus LHRH agonist (P = 0.03), although there was no significant difference in the overall survival. A larger-scaled trial with more statistical power is required to clarify that the former regimen is more beneficial than the latter for newly diagnosed patients with advanced prostate cancer.     

Combination chemotherapy with weekly docetaxel and estramustine for hormone refractory prostate cancer in Japanese patients

Abstract:   The aim is to evaluate the efficacy and toxicity of weekly docetaxel and estramustine for Japanese men with hormone refractory prostate cancer who were treated at a single institution. Twenty eligible patients had histologically proven adenocarcinoma of the prostate with metastases that were progressing despite complete androgen blockade and antiandrogen withdrawal. All of the patients received docetaxel 30 mg/m² weekly (days 1, 8, 15, 22, 29, and 36). After a two week break, the treatment schedule was repeated. Patients were scheduled to receive daily oral estramustine 560 mg/day throughout the protocol. In the serum prostate specific antigen (PSA) response, three (15%) patients achieved a complete response, and 8 (40%) acheived a partial response. Overall survival and time to progression were 13.4 months and 6.4 months, respectively, however sixty-seven percent of the patients had to discontinue treatment because of toxicity. The high toxicity of this protocol suggests that the regimen and/or the timing should be altered for Japanese patients.     

多西紫杉醇治疗激素难治性前列腺癌的研究

目的研究多西紫杉醇3周方案治疗激素难治性前列腺癌的疗效、毒副反应。方法对HRPC患者进行3周方案化疗：多西紫杉醇75mg／m2（第一天）,泼尼松5mg,口服hid,21d为一周期。反应严重的患者之后的给药剂量改为70mg／m2。观察患者的前列腺特异性抗原水平、病灶的变化、毒副反应。结果12例患者经治疗后PSA均有下降,5例PSA下降〉50％。治疗前后PSA中位数分别为28和18,两者比较有统计学差异。复查MRI中2例出现病灶减小。所有患者骨扫描未见新发灶,骨痛的患者中50％有不同程度缓解。主要的副反应为骨髓抑制。结论多西紫杉醇3周方案对于我国HRPC患者的疗效是肯定的,但毒副反应对化疗进程影响很大,本研究建议将不能耐受的患者药物剂量降为70mg／m2。     

A randomized study of docetaxel and dexamethasone with low- or high-dose estramustine for patients with advanced hormone-refractory prostate cancer

OBJECTIVE: To test the combination of docetaxel with two different doses of estramustine in patients with hormone-refractory prostate cancer (HRPC), to improve response rates and to lower side-effects, as docetaxel-based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival. PATIENTS AND METHODS: In all, 72 patients with metastatic HRPC were randomly assigned to receive docetaxel (70 mg/m(2) intravenously, on day 2 every 21 days) and estramustine (3 x 280 mg/day oral starting 1 day before docetaxel, for 5 consecutive days) for arm A, or estramustine (3 x 140 mg/day oral starting 1 day before docetaxel, for 3 consecutive days) for arm B. Premedication with oral dexamethasone at a total daily dose of 16 mg, in divided doses twice a day was administered in arm A on day 1-5 and in arm B on day 1-3. Initially, six cycles were administered. Chemotherapy was restarted after a significant increase in prostate-specific antigen (PSA) level. Patients were monitored for any measurable PSA response and toxicity. RESULTS: Between the arms there was no statistically significant difference in time to progression and overall survival. However, treatment B had less treatment-related toxicity than A. Independent prognostic variables were baseline factors like PSA level, haemoglobin level, Eastern Cooperative Oncology Group performance status, and bone pain at presentation. CONCLUSIONS: In this randomized phase II study the combination of docetaxel and estramustine had substantial activity in HRPC, with a significant incidence of severe toxicity, both haematological and not. Nevertheless, treatment-related toxicity was predictable and manageable. There was no better effect with a higher dose of estramustine with docetaxel than for a lower dose. There was a slight tendency to higher toxicity for high-dose estramustine but this was not statistically significant. The present results support the assertion that estramustine is not necessary in docetaxel-based treatment regimens.     

The androgen receptor in hormone-refractory prostate cancer

Advanced prostate cancer is responsive to hormone therapy that interferes with androgen receptor （AR） signalling. However, the effect is short-lived, as nearly all tumours progress to a hormone-refractory （HR） state, a lethal stage of the disease. Intuitively, the AR should not be involved because hormone therapy that blocks or reduces AR activity is not effective in treating HR tumours. However, there is still a consensus that AR plays an essential role in HR prostate cancer （HRPC） because AR signalling is still functional in HR tumours. AR signalling can be activated in HR tumours through several mechanisms. First, activation of intracellular signal transduction pathways can sensitize the AR to castrate levels of androgens. Also, mutations in the AR can change AR ligand specificity, thereby allowing it to be activated by non-steroids or anti-androgens. Finally, overexpression of the wild-type AR sensitizes itself to low concentrations of androgens. Therefore, drugs targeting AR signalling could still be effective in treating HRPC.     

经尿道前列腺切除术治疗晚期激素非依赖性前列腺癌可行性分析

目的:探讨经尿道前列腺切除术(TURP)在晚期前列腺癌并下尿路症状(LUTS)治疗中的作用。方法:对2004～2009年诊断为晚期前列腺癌合并LUTS的43例患者进行总结,分析TURP术前及术后3、12个月患者的IPSS评分、最大尿流率、以及疾病相关危险因素。结果:术后3个月,非雄激素依赖性前列腺癌患者的IPSS[(9.58±0.33)分]、最大尿流率[(8.96±0.47)ml/s]与术前[(19.60±0.41)分、(4.93±0.68)ml/s]存在显著差异(P<0.05)。随访12个月后IPSS[(15.73±0.66)分]、最大尿流率[(15.67±0.44)ml/s]与术前相比无显著性差异。多因素分析提示术前表现为急性尿潴留的患者术后预后相对较好,激素非依赖前列腺癌患者预后差。结论:TURP治疗晚期激素非依赖前列腺癌合并LUTS的患者,在短期内可以迅速降低IPSS评分,改善生活质量;远期效果不理想。同时,手术本身也可能带来相关并发症,降低患者生存质量。     

Effect of zoledronic acid on metastatic hormone-refractory prostate cancer resistant to taxane, estramustine, carboplatin, and dexamethasone

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.     

Combination chemotherapy with paclitaxel,estramustine and carboplatin for hormone refractory prostate cancer

PURPOSE: The activity of estramustine phosphate is synergistic with paclitaxel against hormone refractory prostate cancer. Moreover, the single agent activity of carboplatin has demonstrated a 17% response rate in measurable disease. Therefore, we conducted a prospective trial to establish more effective chemotherapy consisting of paclitaxel, estramustine phosphate and carboplatin for hormone refractory prostate cancer. MATERIALS AND METHODS: The study included 32 patients with hormone refractory prostate cancer. Prior chemotherapy was accepted. Patients were treated with 100 mg./m.2 paclitaxel intravenously weekly, 10 mg./kg. estramustine phosphate orally daily and carboplatin intravenously to an area under the curve of 6 on day 1 of every 4-week cycle. Treatment was continued until disease progression or excessive toxicity. RESULTS: Of the 32 patients 30 were assessable for response. A median of 7 consecutive cycles was administered per patient. Ten patients had received prior cytotoxic chemotherapy. Levels of prostate specific antigen decreased by greater than 50% in 100% of patients and by greater than 90% in 56.7%. Partial response was obtained in 61.1% of measurable lesions. Consumption of medication for cancer induced pain was reduced in 89.5% of patients. Tumor volume reduction and/or antitumor therapeutic effects were exhibited in 81.0% of patients with positive biopsy. At a median followup of 48 weeks median time to progression was 48 weeks and median overall survival was 95 weeks. Two patients suffered myocardial infarction and hepatic insufficiency, respectively, and discontinued treatment during the first cycle. Major toxicities were grade 3 or 4 anemia in 59.4% of patients, leukopenia in 37.5%, thrombocytopenia in 28.1% and neuropathy in 12.5%. However, all toxicity was temporary and reversible with dose reduction or temporary cessation of chemotherapeutic agents. CONCLUSIONS: Paclitaxel, estramustine phosphate and carboplatin chemotherapy was extremely effective for hormone refractory prostate cancer. Although hematological and neurotoxicity were modest, this therapy may be more manageable with lower doses.     

Immunological monitoring during combination of patient-oriented peptide vaccination and estramustine phosphate in patients with metastatic hormone refractory prostate cancer

BACKGROUND: Additive antitumor effects could be achieved by combination of immunotherapy and cytotoxic agents with no or minimum suppression. METHODS: Thirteen patients positive for human leukocyte antigen (HLA)-A24 or -A2 with metastatic hormone refractory prostate cancer (HRPC) who had failed to respond to the prior-peptide vaccination were entered in the combined peptide vaccination and estramustine phosphate. Conducted immune monitoring on those 13 patients were mainly peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by IFN-gamma productions and peptide-reactive IgG by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Grade 3 arrhythmia or cerebral infarction was observed in two cases, and Grade 1 or 2 dermatologic reaction at the vaccination sites was observed in all 13 cases. Eleven patients who received more than one cycle of treatment were eligible for immunological and clinical evaluation. There was no significant immunosuppression in most cases when the peptide and a half dose (280 mg/day) of estramustine were administrated, whereas severe immunosuppression was observed in the first two patients who received both the peptide and a full dose (560 mg/day) estramustine. Augmentation of peptide-specific CTL precursors or peptide-specific IgG was observed in 6 of 11 or 10 of 11 cases, respectively. Ten of 11 patients showed serum prostate-specific antigen (PSA) level decrease from the baseline including 8 patients with a serum PSA level decrease of > or =50%. CONCLUSIONS: These results encouraged the further evaluation of the combination of peptide vaccination and low-dose estramustine phosphate for metastatic HRPC patients.     

Docetaxel, with or without estramustine phosphate, as first-line chemotherapy for hormone-refractory prostate cancer: results of a multicentre, randomized phase II trial

OBJECTIVE

To report the results of a randomized phase II trial of docetaxel with and without estramustine phosphate (EP) in patients with hormone‐refractory prostate cancer (HRPC).

PATIENTS AND METHODS

Patients with progressive HRPC were randomized to receive docetaxel 70 mg/m² on day 1 (arm A), or docetaxel 70 mg/m² on day 2 plus oral EP three times daily, at a total daily dose of 840 mg, on days 1–5 (arm B). The primary objective of the trial was to evaluate the activity of the treatments in terms of the response in prostate‐specific antigen (PSA) level.

RESULTS

Forty‐five of the 49 patients centrally randomized to arm A and 44 of the 46 in arm B were evaluable for activity. The PSA level decreased by ≥50% in 40% of the patients in arm A and in 75% of those in arm B. The median time to PSA progression was 20 weeks in arm A and 30 weeks in arm B. The patients in arm B had an improvement in pain over time.

CONCLUSION

These data support the existence of a possible advantage in combining docetaxel and EP, which should be verified in a specific randomized phase III study.     

Safety and efficacy of docetaxel,estramustine phosphate and hydrocortisone in hormone‐refractory prostate cancer patients

Objective: To assess the combination of docetaxel (DTX), estramustine phosphate (EMP) and hydrocortisone for patients with hormone‐refractory prostate cancer (HRPC). Methods: A total of 63 patients with HRPC were treated with a chemotherapeutic regimen including DTX, EMP, and hydrocortisone. Clinical and pathological features were correlated to serum prostate‐specific antigen (PSA) recurrence and survival rates. Incidence and degree of toxicities were also retrospectively reviewed. Results: A median of 11 courses of chemotherapy was administered per patient. PSA levels decreased by >50% in 32 (51%) patients and >90% in 18 (29%) patients. Median time to PSA progression was 6 months (range from 1 to 41 months) and median time of overall survival was 14 months (range from 1 to 56 months). In a univariate analysis to predict overall survival, PSA, hemoglobin, alkaliphosphatase, and performance status prior to the chemotherapy were significant factors. Despite grade 3–4 neutropenia in 87% of patients, grade 5 interstitial pneumonia in one patient and grade 4–5 myocardial infarction in two patients were recognized, the regimen seemed to be relatively safe. Conclusions: Combination chemotherapy with DTX, EMP and hydrocortisone provides survival benefits for patients with HRPC with an acceptable toxicity profile. We need to further evaluate who might benefit most from this regimen.     

Bi-weekly epirubicin, etoposide and low-dose dexamethasone for hormone-refractory prostate cancer

BACKGROUND: Recent studies have demonstrated the efficacy and favorable toxicity profile of chemotherapy regimens given at lower doses and frequent intervals. The aim of our study was to evaluate the efficacy and toxicity of a bi-weekly chemohormonal regimen consisting of epirubicin, etoposide, and low-dose dexamethasone (EED) in patients with hormone-refractory prostate cancer (HRPC). METHODS: We treated a total of 32 patients who had failed hormonal therapy and antiandrogen withdrawal. Chemotherapy was given every 2 weeks and consisted of epirubicin (30 mg/m2 intravenously, day 1) and etoposide (50 mg/m2 orally, days 1-7). Dexamethasone (1.5 mg orally, every other day) was given continuously until disease progression. Twenty patients (63%) had received prior treatment with estramustine phosphate. Each patient's pain response was evaluated according to analgesic use. Toxicity was graded using the Common Toxicity Criteria (version 2.0). RESULTS: Prostate-specific antigen (PSA) levels showed a decline of 50% or greater in 16 of 32 patients (50%, 95% confidence interval [CI], 32-68%) with a median time to biochemical progression of 5 months (range, 4-9 months). The median survival for all patients was 10.5 months (range, 3-35 months). Four of 10 patients (40%) with measurable soft tissue lesions achieved partial response according to standard criteria. Eleven of 23 symptomatic patients (48%, 95% CI, 27-69%) experienced an improvement in pain with a median duration of 6 months. The regimen was tolerated well by the patients, with only four patients (12%) having grade 3 leukopenia. CONCLUSION: Chemohormonal EED regimen proved to be active and well-tolerated in patients with HRPC.     

Inhibition of prostate cancer growth by estramustine and colchicine

Hormone-refractory prostate cancer continues to be associated with a very poor prognosis. Agents that inhibit microtubule function have been found to be cytotoxic to prostate cancer cells in preclinical and clinical settings. It was the aim of this study to assess the activity of estramustine and colchicine, two microtubule inhibitors, in hormone-refractory prostate cancer. In clinically achievable concentrations, the combination of estramustine and colchicine was cytotoxic to both the Dunning rat prostate adenocarcinoma cell line MAT-LyLu (MLL) and human prostate cancer cells (PC-3). Microtubule function was assessed in vitro to evaluate possible mechanisms of action. In motility and cell cycle analysis assays, estramustine and colchicine inhibited cellular motility but not cell cycle transit. In vivo, these two agents both inhibited the growth of implanted Dunning rat prostate adenocarcinoma MLL cells but did not appear to have additive effects. The use of oral colchicine in the treatment of hormone-refractory prostate cancer requires further investigation.     

Adenovirus-mediated inhibition of survivin expression sensitizes human prostate cancer cells to paclitaxel in vitro and in vivo

BACKGROUND: Improvements in the response rates to chemotherapy would represent an important advancement in the care of patients with metastatic prostate cancer. There is accumulating evidence that Survivin, a member of the inhibitor of apoptosis (IAP) family, is associated with both cancer progression and drug resistance. The purpose of this study is to investigate the role of Survivin in paclitaxel-resistance and whether the targeting of Survivin sensitizes prostate cancer cells to paclitaxel. METHODS: Human prostate cell lines PC-3, DU-145, and LNCaP were infected with replication-deficient adenoviruses encoding either wild-type Survivin [pAd-S(WT)], to examine Survivin overexpression effects, or a phosphorylation-defective Survivin Thr34 --> Ala dominant negative mutant [pAd-S(T34A)], to examine Survivin inactivation effects. The effects of wild-type or mutant Survivin on spontaneous and paclitaxel-induced apoptosis were investigated both in vitro and in vivo. RESULTS: Forced overexpression of wild-type Survivin with pAd-S(WT) increased resistance to paclitaxel in all cell lines, both in vitro and in vivo. Inhibition of Survivin using pAd-S(T34A) resulted in a significant increase in the rate of spontaneous and paclitaxel-induced apoptosis in all cell lines, both in vitro and in vivo. This effect was abolished by co-treatment with VAD-CHO (Calbiochem, San Diego, CA), a pan-caspase inhibitor, indicating that Survivin normally mediates resistance to paclitaxel through suppression of caspase-mediated apoptosis. CONCLUSIONS: Survivin mediates paclitaxel-resistance in prostate cancer cells. The inhibition of Survivin sensitizes prostate cancer cells to paclitaxel-induced apoptosis through a caspase-dependant mechanism in vitro and in vivo.     

The use of estramustine phosphate in the modern management of advanced prostate cancer

What’s known on the subject? and What does the study add? Estramustine phosphate has anti‐tumour properties and it improves patient outcomes if combined with other chemotherapy agents such as doeetaxel. The efficacy of estramustine phosphate in selected patients and its safety profile, provided used with any low‐molecular‐weight heparin support its use as a second‐line treatment in hormone‐resistant prostate cancer.

OBJECTIVES

• ? Estramustine phosphate is a nitrogen mustard derivative of estradiol‐17β‐phosphate and has anti‐tumour properties.
• ? Interest in estramustine has been renewed because of the results of clinical studies showing improved patient outcomes if estramustine is combined with other chemotherapy agents such as docetaxel.

PATIENTS AND METHODS

• ? Relevant clinical studies using chemotherapy combinations including estramustine are discussed.
• ? Efficacy and safety outcomes are summarized.

RESULTS

• ? Combination therapy with estramustine and docetaxel can increase PSA response rates, improve quality of life and increase median patient survival compared with chemotherapy regimens that do not include estramustine.
• ? Although the overall tolerability of estramustine is favourable, its use can be associated with an increased risk of thromboembolic events.

CONCLUSIONS

• ? The identification of suitable patient groups and the effective management of the risk of thromboembolism with the adjunct of low‐molecular‐weight heparins support the use of estramustine as an effective second‐line treatment strategy in hormone‐resistant prostate cancer.
• ? These promising findings warrant further investigation in a randomized clinical trial.

     

Dramatic decline in prostate-specific antigen by withdrawal of estramustine phosphate in hormone refractory prostate cancer

Prostate-specific antigen (PSA) decline after discontinuation of estramustine phosphate (EMP) is extremely rare. We report a case with dramatic PSA decline after withdrawal of EMP. A patient with prostate cancer had been treated with luteinizing hormone-releasing hormone and EMP. After refractory, EMP was withdrawn. After withdrawal of EMP, PSA dramatically decreased from 214 ng/mL to 3.71 ng/mL (98.5% decline) and remained low for more than 17 months. In association with PSA decline, lumbago and metastatic lesions improved. We should be aware of this phenomenon and the discontinuation of EMP is recommended in patients with rising PSA after an initial response to EMP.     

Therapeutic options in androgen-independent prostate cancer: building on docetaxel

Of men with metastatic prostate cancer who undergo androgen ablation, 70-80% respond rapidly to therapy, as manifested by a reduction in prostate cancer-related symptoms and declines in serum prostate-specific antigen (PSA) level. Unfortunately, after a median of 18-24 months, nearly all patients with metastatic prostate cancer will progress to androgen independence. Until recently the standard of care for treating hormone-refractory prostate cancer (HRPCa) was the combination of mitoxantrone and prednisone, which palliated bone pain but did not extend survival. Two randomized trials with > 1700 patients showed for the first time a survival benefit for patients with HRPC treated with chemotherapy; when compared with mitoxantrone-based therapy, docetaxel based-therapy reduced the risk of death by 20-24%. Future trials in HRPC are attempting to improve the efficacy of docetaxel by incorporating new agents targeting angiogenesis, apoptosis, and signal transduction pathways; there is promising activity for these novel combinations in phase I and II studies. Concepts are also being refined about definitions of response and progressive disease, patient eligibility criteria, and the validity of surrogate markers of efficacy and survival, as shown by changes in PSA level.     

High dose pulse calcitriol, docetaxel and estramustine for androgen independent prostate cancer: a phase I/II study

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: A total of 24 patients, including 11 who were chemotherapy na?ve 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 na?ve patients (55%) met prostate specific antigen response criteria. One of 11 patients (9%) treated with prior docetaxel met these criteria. CONCLUSIONS: High dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule.