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PubMed1985

Approaches to prostatic cancer chemotherapy using the Dunning R3327H prostatic adenocarcinoma.

Androgen-responsive cells: To determine if testosterone or dihydrotestosterone is the main trophic hormone of prostatic adenocarcinoma, we have treated Dunning R3327H prostatic adenocarcinoma-bearing rats with 6-methylene progesterone, which blocks conversion of testosterone to dihydrotestosterone. Copenhagen-Fisher rats were treated with steroid (20 mg/Kg daily) immediately following implantation of tumor and thereafter for 117 days. There was a 92% inhibition of growth of tumors and a lesser effect upon prostate and seminal vesicles. Tumor-free body weights remained unchanged. Both treated and untreated tumors had equivalent DNA content on a per weight basis. This result supports the thesis that prostatic adenocarcinoma requires dihydrotestosterone for growth. Androgen-insensitive cells: Advanced prostate cancer does not respond to endocrine therapy but is temporarily controlled by the cytotoxic steroid estramustine. The latter shows significant selective binding to prostatic protein. To develop chemotherapeutic agents that will control androgen-insensitive cells and possess improved selectivity for prostatic protein, we have studied a number of steroids for their ability to displace 3H-labeled estramustine from prostatic cytosolic proteins. Surprisingly, a carbamido substituent at the C17 position was found to confer significant binding affinity for prostatic estramustine-binding protein. Extension of this structural characteristic to the estramustine type of molecule is being studied.

5-alpha Reductase Inhibitors↗
PubMed1987

Testosterone-induced DNA synthesis in cultured rat ventral prostate: effects of estracyt and its derivatives.

Testosterone-induced DNA synthesis in cultured rat ventral prostate was used to compare the direct effects of Estracyt and Emcyt with that of their metabolite, estramustine, and their carrier-hormone, oestradiol-17 beta on prostatic growth. In serum-supplemented medium (5-20% FCS), all the compounds were equally effective in suppressing testosterone stimulated DNA synthesis which was reduced by between 40-50%, whereas in serum-free medium the estramustine compounds were consistently less effective than oestradiol-17 beta. In the presence of 4 X 10(-9) M testosterone in serum-free medium, stimulated DNA synthesis was reduced by 15-30% following incubation with 4 X 10(-7) M of Estracyt, Emcyt and estramustine and by 60% with 4 X 10(-7) M oestradiol-17 beta. Thus, none of the estramustine compounds appear to offer any selective advantage over that of oestradiol-17 beta in suppressing prostatic DNA synthesis at the target tissue level.

Animals↗
PubMed1981

Cardiovascular complications in the treatment of prostatic carcinoma.

Cardiovascular complications in patients with carcinoma of the prostate have been studied in relation to 3 methods of treatment, namely stilboestrol, estramustine phosphate (Estracyt) and bilateral orchiectomy. One hundred and sixteen patients were studied over a 4-year period on a prospective basis, 48 being treated with stilboestrol, 31 with estramustine and 37 with bilateral orchiectomy. The incidence of the cardiovascular side effects of these 3 treatment regimes in the first year of treatment was recorded after the patients had been divided into those with localised (MO) disease and advanced disease with metastases (M1). In patients treated with stilboestrol 29% had cardiovascular complications with a mortality rate of 16%. With estramustine 25% had complications with a 16% mortality rate, but with orchiectomy the complication rate was only 8% with a 3% mortality rate. It is recommended that stilboestrol and estramustine phosphate should not be used in the presence of cardiovascular disease and that the primary form of treatment in prostatic carcinoma should be bilateral orchiectomy, especially in patients with localised disease.

Aged↗
PubMed2004

[Docetaxel and prostate cancer].

Prostate cancer is currently the most-frequency malignancy in men, and the second cause of death from cancer in the Western world. Once the disease has metastasized, palliative treatment is the rule. First-sine therapy consists in surgical or chemical castration, associated or not with anti-androgens. This treatment approach is active in 80% cases but failures occur within 12-18 months. When the disease becomes refractory to hormone therapy, few alternatives are available. The combination of mitoxantrone-steroids improves clinical symptoms, namely by reducing pain, but does not improve patient survival. Both docetaxel and estramustine act through microtubules and synergistic interactions have been shown between these two compounds. Recently, several studies have demonstrated the efficacy of a combination of estramustine and taxanes, and in particular docetaxel. Phase II trials using docetaxel monotherapy have demonstrated responses rates concerning PSA of 45 to 58% and objective response of 33% and 40%. Combination with estramustine increases the biochemical response rate from 45% and 74%. A randomized phase II trial revealed the superiority of this combination compared to mitoxantrone in terms of response rate and clinical benefit. The results of phase III trials are still not available, in particular as concerns survival, but the combination docetaxel-estramustine appears very promising, even though the ideal therapeutic protocol is still under evaluation.

Antineoplastic Agents, Phytogenic↗
PubMed1991

Mechanism based chemotherapy for prostate cancer.

Estramustine offers a mechanistically novel therapy for the treatment of prostatic cancer. The drug is composed of oestradiol coupled to nor-nitrogen mustard. The cytotoxic properties of estramustine act independently of its constituent molecules. In vivo and in vitro studies indicate that the drug binds microtubule associated proteins and inhibits microtubule regulated processes. We have lately shown that micromolar levels of estramustine inhibit selected processes in mitosis, suggesting that certain classes of microtubules and/or MAPs are differentially sensitive to the drug. New clinical trials using estramustine and vinblastine on patients with advanced hormone refractory disease suggest that the combination of two antimicrotubule agents acting by means of different target molecules may be important clinically.

Animals↗
PubMed1976

The absorption metabolism, and excretion of Estracyt (NSC 89199) in patients with prostatic cancer.

Estraumustine phosphate (estradiol, 3-N-[bis(2-chloroethyl)-] carbamate-17beta-dihydrogenphosphate (Estracyt) labeled with 3H in the estradiol moiety and 14C in the carbamate moiety was synthesized, and its absorption, metabolism, and excretion were studied after oral administration to three patients with prostatic carcinoma. One of the patients was also given the same dose by intravenous injection. In addition to monitoring isotope levels in peripheral blood, urine, and feces, samples of portal vein blood were obtained through a catheter in the umbilical vein. Analyses of portal blood samples revealed that most of the estramustine phosphate was dephosphorylated to estramustine during absorption. Estramustine was found to be the major metabolite in peripheral blood after oral as well as after intravenous administration. The urinary excretion data appeared to warrent the conclusion that most of the carbamate ester of estraumustine is hydrolyzed before it is excreted. In the patient given estramustine phosphate by both routes the absorption of the compound when given by mouth was found to be approximately 75 per cent.

Administration, Oral↗
PubMed1999

Review of phase II hormone refractory prostate cancer trials.

In men with hormone refractory metastatic prostate cancer, single agents have demonstrated an objective response when using a response rate greater than standard treatment in prior National Prostate Cancer Project (NPCP) trials. Among these agents are methotrexate, cisplatin, 5-fluorouracil, cyclophosphamide, doxorubicin, estramustine, methyl N-(2-chloroethyl)-N'-cyclohexyl-Nnitrosourea (CCNU), 5-(3,3-dimethyl1-triazenyl)1H-imidazole-4-carboxamide (DTIC), and vinblastine. Other combinations of protocols have been previously evaluated. Currently under review is a 1 4-year follow-up on an adjuvant trial (NPCP 900/1000) where all patients had a bilateral pelvic lymphadenectomy. These patients were then randomized to surgery or radiation, and received either cyclophosphamide, estramustine, or no therapy for 2 years. Clinical results showed there was no difference in disease-free survival or survival rates between those patients in the group who had T3 prostate cancer, and those with negative pelvic lymph node dissection. The drugs diethylstilbestrol, megestrol, or streptozocin have been used. In clinical trials, the single agent diethylstilbestrol usually had a better effect. Combinations of estramustine with vinblastine were also effective when compared with the results of standard treatment. When comparing patients who relapsed from hormone refractory prostate cancer, there was no significant statistical response rate difference (P = <0.05) in patients who were offered either flutamide or estramustine. To determine more accurately the positive results from these trials, the pre-prostate-specific antigen (PSA) era of stable disease must be re-evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation.

The aim of this study was to find factors that could explain the accumulation difference of mitoxantrone in the BCRP1-negative GLC4-MITO cell line compared to GLC4. Comparative genomic hybridisation (CGH) was applied to determine chromosomal differences between GLC4 and GLC4-MITO. Comparative genomic hybridisation analysis revealed gain of 2q, 6p, 9q, 13q, 14q, 15q, 19q and Xp and loss of 1p, 2q, 3p, 3q, 4q, 6q, 8q, 11p, 16p, 17q, 18p, 20p and Xq. In the over-represented chromosomal areas, seven transporter genes were identified: ABCB6, ABCB2 (TAP1), ABCB3 (TAP2), ABCF1 (ABC50), ABCC10 (MRP7), ABCA2 (ABC2) and ABCC4 (MRP4). No RNA or protein upregulation was observed for ABCB6, ABCF1, ABCC10, ABCC4, ABCB2 and ABCB3, but an increased expression was detected for ABCA2 mRNA in GLC4-MITO. ABCA2 is known to be involved in resistance to estramustine. In the MTT assay, GLC4-MITO was two-fold resistant to estramustine compared to GLC4. Coincubation with estramustine and mitoxantrone increased mitoxantrone accumulation in GLC4-MITO, while this was not affected in GLC4. This suggests that estramustine is able to block mitoxantrone efflux in GLC4-MITO cells. These data reveal that cellular reduction of mitoxantrone in a mitoxantrone-resistant cell line is associated with overexpression of ABCA2.

ATP-Binding Cassette Transporters↗
PubMed1994

Morphologic and immunohistochemical changes in prostate cancer after preoperative hormonal therapy. A comparative study of radical prostatectomies.

BACKGROUND: Estramustine phosphate (EMP) and flutamide (FL) were used as reversible preoperative hormonal drugs in the surgical treatment of patients with localized prostate cancer. METHODS: The authors descriptive and quantitatively examined the morphologic and immunohistochemical changes in 40 of 200 step-sectioned radical prostatectomies, obtained after treatment with EMP (25 patients) and with FL (15 patients). Of these, 28 pretreatment needlecore biopsies were available. RESULTS: Every specimen contained adenocarcinoma. Understaging was found in 50% of the cases and a higher Gleason score in 70%. Benign glands underwent atrophy and squamous metaplasia. Treated tumors showed cytoplasmic vacuolization, nuclear pyknosis, fibrosis and lymphocytic infiltrates. The EMP group had an 84% (P < 0.05) higher mean total regression score than the FL group. Estramustine phosphate induced a 56% (P < 0.05) and a 34% decrease in tumoral prostate specific antigen and prostate specific acid phosphatase intensity scores, respectively, versus 29% and 32% after FL. The mean proliferating cell nuclear antigen (PCNA) labeling index and the mean mitotic index of the EMP group were 52% (P < 0.05) and 70% (P < 0.05) lower than those measured in the FL group. Each FL-treated tumor and 92% of EMP-treated tumors expressed chromogranin A (ChrA); ChrA labeling correlated significantly with PCNA labeling. Seventy-six percent of EMP-treated specimens revealed venous thrombosis. CONCLUSIONS: Estramustine phosphate induces important morphologic and immunohistochemical changes in prostate cancer with an apparent decrease of secretory and proliferative activity when compared with FL-treated tumors. These changes represent pitfalls in the diagnosis and grading of treated carcinomas. Nearly every treated adenocarcinoma of the prostate has neuroendocrine differentiation, showing increasing ChrA labeling with higher tumor stage. A significant correlation between tumor proliferation and neuroendocrine differentiation was noticed in this small cohort of patients. There was a high incidence of periprostatic venous thrombosis after EMP treatment.

Acid Phosphatase↗
PubMed2006

A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: second line taxane-based therapy after first-line epothilone-B analog ixabepilone (BMS-247550) therapy.

BACKGROUND: Epothilones and taxanes interfere with microtubule function. Ixabepilone, which is an epothilone-B analog, has activity against taxane-resistant cell lines and as first-line therapy for men with hormone-refractory prostate carcinoma (HRPC). Clinical cross-resistance of ixabepilone and taxanes in HRPC is unknown. METHODS: Records were evaluated retrospectively from patients with HRPC who were treated on a randomized Phase II trial of ixabepilone with or without estramustine and who subsequently received taxane chemotherapy. Posttherapy declines in prostate-specific antigen (PSA) levels and time to PSA progression were defined by consensus criteria. The median survival was evaluated by using the Kaplan-Meier method. RESULTS: Forty-nine patients who received ixabepilone with estramustine (28 patients) or without estramustine (21 patients) subsequently received second-line taxane therapy. Second-line PSA declines > or = 50% were achieved by 51% of patients (95% confidence interval [95% CI], 33-66%). Second-line PSA declines > or = 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline > or = 50% with ixabepilone, compared with 33% of patients (95% CI, 13-59%) who did not (P = 0.08). Patients who discontinued first-line ixabepilone treatment for disease progression were less likely to achieve a PSA decline > or = 50% in response to second-line, taxane-based therapy compared with patients who discontinued for toxicity or patient preference (36% vs. 71%; P = 0.01). CONCLUSIONS: Second-line taxane chemotherapy after ixabepilone resulted in a substantial frequency of PSA declines. Although patients with ixabepilone-refractory disease were less likely to respond to second-line taxane chemotherapy, 36% did achieve a PSA response. These findings were consistent with incomplete clinical cross-resistance between the taxanes and the epothilones.

Aged↗
PubMed1982

Influence of pituitary and adrenocortical hormones on prostatic secretion protein, a major protein in rat prostate.

Prostatic secretion protein (PSP) is an androgen-sensitive, quantitatively important protein in rat ventral prostate which has been shown to inhibit the nuclear uptake and decrease the DNA-binding capacity of the androgen-receptor complex. In the present study, the influence of the pituitary, adrenals, and gonads on the concentration of PSP in the prostate was studied. Hypophysectomy decreased the concentration of PSP to about 10% of the control level, an effect similar to that obtained by castration. No effects on prostatic wet weight or PSP concentration were observed following substitution of hypophysectomized rats with human growth hormone, rat prolactin, or rat growth hormone. On the other hand, PSP concentration as well as wet weight of the prostate were normalized in hypophysectomized rats after administration of testosterone propionate. These results are in line with a direct extrahypophyseal effect of androgens on the prostate. Adrenalectomy did not affect the concentration of PSP, nor the wet weight of the prostate. Administration of estramustine decreased the wet weight of the prostate but did not affect the prostatic concentration of PSP in normal rats. Combined treatment with testosterone propionate and estramustine seemed to increase both the wet weight and the concentration of PSP more than administration of testosterone propionate alone. These results indicate a synergistic effect between estramustine and testosterone propionate.

Adrenal Cortex Hormones↗
PubMed2002

Drug resistance in prostate cancer cell lines is influenced by androgen dependence and p53 status.

Chemotherapeutic drug resistance remains a significant obstacle in the control of prostate cancer. The influence of p53 and androgen status on the drug response of new cell lines from normal, benign and primary tumour epithelium was investigated. The prostate cell lines 1542-NPTX, BPH-1, 1542-CP(3)TX, 1532-CP(2)TX, 1535-CP(1)TX and LNCaP were exposed to TD(50) doses of etoposide, vinblastine and estramustine for a period of 24 h and re-incubated for a further 4 days before measuring the cell viability by crystal violet vital dye staining assay. The virus-transformed cell lines were found to be approximately ten times more sensitive to etoposide and vinblastine than the non virus-transformed LNCaP cell line. Estramustine proved to be the least toxic drug. The LNCaP cell line emerged as DHT-sensitive against nanomolar concentrations of 5alpha-dihydrotestosterone in charcoal-stripped growth medium. The virus-transformed cell lines were DHT-insensitive. Induction of p21 by (60)Co gamma-irradiation was used to assess the functionality of the p53 gene. p21 induction in the LNCaP cell line reached a peak 7.5 h post-irradiation. No significant p21 induction occurred in the virus-transformed cell lines. We show that the androgen-independent tumour cell lines are more sensitive to etoposide and vinblastine than the androgen dependent cell line, LNCaP. Except for LNCaP cells, etoposide and vinblastine were found to be three- to ten-fold more effective than estramustine. In the benign hyperplasia cell line, BPH-1, only etoposide is highly effective. Etoposide and vinblastine were found to effectively inactivate the androgen-independent cell lines, in which p53 is dysfunctional.

Androgens↗
PubMed2004

Five-year outcomes after neoadjuvant chemotherapy and conformal radiotherapy in patients with high-risk localized prostate cancer.

OBJECTIVES: To describe the 5-year outcomes of patients with high-risk localized prostate cancer treated with neoadjuvant estramustine and vinblastine followed by concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT). METHODS: A total of 23 patients completed therapy consisting of two 8-week cycles of vinblastine, weekly as 4 mg/m2, followed by 8 weeks of concomitant chemotherapy and 3D-CRT. Estramustine was given daily at 10 mg/kg in three divided doses. 3D-CRT consisted of a total dose of 7560 cGy. RESULTS: Assessable patients include 9 with Stage T3 or greater tumors and 5 with lymph node metastasis at diagnosis. All patients had a Gleason score 7 or greater. The median follow-up was 60 months. Of the 23 assessable patients, 15 (65%) experienced biochemical relapse by American Society for Therapeutic Radiology Oncology criteria. The median time to prostate-specific antigen relapse was 12 months (range 7 to 16). Five patients (22%) developed metastases. The median time to metastasis had not been reached by last follow-up. Of the 23 assessable patients, 11 (48%) received no additional therapy and had noncastrate testosterone levels. Six patients had no evidence of disease and 9 patients were receiving androgen blockade. Three patients died (one of prostate cancer and two of other diseases). CONCLUSIONS: A substantial proportion of patients with unfavorable-risk localized prostate cancer achieved long-term disease control with estramustine and vinblastine and concurrent 3D-CRT, no significant long-term toxicities were seen and 48% underwent no further therapy after RT. These long-term findings support the continued study of chemotherapy combined with RT as a potential alternative to prolonged androgen deprivation.

Adenocarcinoma↗
PubMed1998

Cloning and sequencing of human betaIII-tubulin cDNA: induction of betaIII isotype in human prostate carcinoma cells by acute exposure to antimicrotubule agents.

Antimicrotubule drugs are used as chemotherapeutic agents due to their effects on essential cellular functions such as mitosis, organelle transport and maintenance of cell shape. When used in combination, paclitaxel with estramustine or vinblastine has demonstrated activity against hormone refractory prostate cancer. To understand the mechanism of resistance that develops in patients as a result of antimicrotubule drug therapy, we exposed human prostate carcinoma cells to IC20 and IC40 doses of estramustine, paclitaxel or vinblastine for 48 h and examined the beta-tubulin (the cellular target) isotype composition. The results revealed an increase in the betaIII-tubulin isotype as a result of drug treatment both at protein and message levels. In addition, examination of human brain cell lines with different intrinsic levels of betaIII showed that cell lines with higher betaIII levels were more resistant to paclitaxel. These results are in agreement with our previous findings in human prostate carcinoma cell lines that were made resistant to estramustine or paclitaxel and suggest an important function for betaIII in antimicrotubule drug resistance. Also, the complete coding sequence of human betaIII tubulin reported here will provide molecular tools for future investigations.

Amino Acid Sequence↗
PubMed2000

Combination chemotherapy following adrenal suppression in androgen- independent prostate cancer.

OBJECTIVES: Recent trials with modern chemotherapy have demonstrated activity in androgen-independent prostate cancer, but all focused on patients with progression following androgen suppression or antiandrogen withdrawal. Limited data are available on the activity of chemotherapy in androgen-independent, hormone-refractory (progressing following adrenal suppression) prostate cancer. We evaluated the activity of estramustine combined with vinblastine in this subset of androgen-independent prostate cancer. METHODS: From January 1995 until April 1999, 19 patients with hormone-refractory prostate cancer received estramustine 140 mg p.o., three times daily along with weekly vinblastine 5 mg/m(2). RESULTS: A decrease in prostate-specific antigen of 50% or more was noted in 12 patients (63.1%, 95% CI 38.3-83.7%). The median decrease in prostate-specific antigen was 71.2% (range 50.5-85.2%). None of the 7 patients with measurable soft-tissue disease showed an objective response. The median survival from onset of chemotherapy was 6 (range 1.4-27.7) months and from initiation of adrenal suppression 16.9 (range 3.8-40. 5) months. CONCLUSIONS: The combination of estramustine and vinblastine is capable of inducing activity in androgen-independent prostate cancer progressing after adrenal suppression. In our small sample, the survival rate was low, and we obtained no response in soft-tissue sites. Future prospective trials are needed to determine the benefit of sequential versus simultaneous incorporation of adrenal suppression with chemotherapy in the management of androgen-independent prostate cancer.

Adult↗
PubMed2001

Current status of cytotoxic chemotherapy in hormone refractory prostate cancer.

Adenocarcinoma of the prostate is the most prevalent neoplastic disease in men and continues to be a major cause of morbidity and mortality. Death from prostate cancer is associated with objective and biochemical progression following hormonal manipulations often described as hormone refractory prostate cancer (HRPCA). Therapy for HRPCA is primarily palliative and therapeutic efficacy has to be balanced against potential treatment-related side effects. Therapeutic efficacy may be assessed by evaluating the percentage of patients obtaining a PSA decline of > 50%, evaluating the response of bidimensionally measurable disease or by improvements in quality of life assessments. The most effective cytotoxic therapies at the present time seem to be combinations of estramustine phosphate with taxanes and etoposide. Regimes employing ketoconazole with estramustine, vinblastine or bisphosphonates seem to be worthy of further evaluation. Mitoxantrone has an impressive palliative effect in patients, particularly when combined with hydrocortisone. Oral chemotherapeutic regimens with a combination of estramustine phosphate, cyclophosphamide and prednisone appear to offer a less toxic alternative. For the future we need prospective randomized clinical phase-III studies, prognosticators identifying patients as being at high or low risk who might benefit from different therapeutic approaches and generally binding eligibility and response guidelines in order to be able to compare trials of different therapeutic approaches.

Anthracyclines↗
PubMed1991

Expression of Ki-67--a proliferation-associated antigen--in prostatic cancer.

The expression of the proliferation-associated antigen Ki-67 was studied in human prostatic cancer. The antigen was analyzed with an immuno-histochemical technique in TUR specimens. A correlation was seen between Ki-67 positivity and differentiation grade. All TUR specimens (15/15) with poorly differentiated carcinomas expressed the antigen. Moderately differentiated carcinomas constituted an intermediate group and slightly less than half of the cancers (12/27) were positive for the antigen. Only one of the highly differentiated carcinomas (1/12) expressed the antigen. All TUR specimens from patients with benign prostatic hyperplasia (8/8) were negative. The effect on Ki-67 positivity was also investigated in a human prostatic cancer heterotransplanted to nude mice and subjected to ionizing irradiation with or without concomitant estramustine treatment. The antigen expression was compared with that seen in tumour tissues from untreated mice and from mice treated with estramustine alone. A pronounced effect was seen in the combination treatment group with an approximately 50% reduction of the Ki-67 positive cells. The results are discussed in relation to prognosis and follow-up after radiation therapy and the possible use of estramustine in combination with radiation therapy.

Animals↗
PubMed2006

Weekly docetaxel/estramustine phosphate in patients with increasing serum prostate- specific antigen levels after primary treatment for prostate cancer: a phase II trial of the Minnie Pearl Cancer Research Network.

PURPOSE: Docetaxel alone or in combination with estramustine prolongs survival in patients with metastatic hormone-refractory prostate cancer. The role of chemotherapy is undefined in the treatment of patients who develop an increasing serum prostate-specific antigen (PSA) level after primary therapy but have no detectable metastases. This phase II study was performed as a preliminary evaluation of the feasibility and efficacy of weekly docetaxel/estramustine in patients with prostate cancer and increasing serum PSA levels. PATIENTS AND METHODS: Between March 2001 and September 2003, 34 patients entered this phase II trial. All patients had biopsy-proven adenocarcinoma of the prostate and had increasing PSA levels but no clinically or radiographically detected metastases after primary therapy. All patients received docetaxel 35 mg/m(2) intravenously on days 1, 8, and 15 and estramustine phosphate 140 mg 3 times daily for 7 doses, beginning the evening before each dose of docetaxel. Treatment courses were repeated at 28-day intervals, and responding patients received a total of 6 courses. RESULTS: Thirty-one patients (91%) completed 6 courses of treatment. Thirty-two of 33 evaluable patients (97%) had a decrease in serum PSA level of > 50% during treatment, and 27 patients (82%) had normalization of serum PSA level. The median progression-free survival was 28 months, with 33% of patients progression free at 3 years. This treatment regimen was well tolerated with no myelosuppression-related complications or uncommon grade 3 nonhematologic toxicity. CONCLUSION: Treatment with weekly docetaxel and estramustine is feasible and active in patients with prostate cancer and increasing serum PSA levels. However, the benefit of early treatment versus treatment when clinical metastases are detected requires demonstration in a randomized phase III trial.

Aged↗