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At least 19 recordsLinked to original sources
PubMed1984

Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis.

Adjuvant therapy after total mastectomy and axillary clearance in postmenopausal women with breast cancer and axillary node metastasis was assessed; chemo-endocrine therapy (cyclophosphamide, methotrexate, fluorouracil, prednisone, and tamoxifen; CMFp + T) was compared with endocrine therapy (prednisone and tamoxifen; p + T), and with no adjuvant treatment in 463 patients aged less than or equal to 65 years. Endocrine therapy was compared with no adjuvant therapy in 320 patients aged 66-80 years. At median follow-up of 36 months, disease-free survival was significantly longer in CMFp + T patients than in p + T or control patients; p + T also significantly increased disease-free survival. There were no significant differences in overall survival between the randomised groups. In analyses of patterns of first failure, chemo-endocrine therapy reduced local, regional, and distant relapses, whereas endocrine therapy reduced local and regional recurrences only.

Aged↗
PubMed1997

[Newly-developing therapies of pancreatic cancer--immunotherapy, gene therapy, differentiation therapy, endocrine therapy and others].

Pancreatic cancer is extremely resistant to various cancer therapies, however, variety of new therapies for pancreatic cancer have been investigated: (1) immunotherapy including cytokines like TNF, adoptive immunotherapy with lymphokine-activated killer cells or cytotoxic T-lymphocytes, and tumor vaccines using mutated Ki-ras oncoprotein or irradiated tumor cells which were transfected by cytokine genes; (2) gene therapy including transfer of cytokine genes or antisense Ki-ras oncogene, and a combination of gene transfer of herpes simplex virus thymidine kinase and subsequent administration of ganciclovir; (3) differentiation therapy including a quinolinone derivative, vesnarinone; (4) endocrine therapy including cholecystokinin-receptor antagonist, CR1505 or L364,718; (5) heavy water, and etc. All of these therapies will be applied for the treatment of pancreatic cancer in the near future.

Animals↗
PubMedDate not supplied

3H-thymidine autoradiography and cytophotometric analysis of needle aspirates from human tumours during radiation therapy, endocrine therapy and chemotherapy.

Cell kinetic variables in human tumours were investigated before and during therapy. Tumour cell material was collected by sequential thin needle aspiration biopsy. Small variations in DNA replication could be detected by 3H-thymidine autoradiography. In tumours with a high rate of replication, therapy induced changes could also be detected with flow cytometry and static cytophotometry. Endocrine treatment with glucocorticoids, radiation therapy, and chemotherapy were associated with reduced rates of DNA replication in malignant lymphomas. The conformity between labelling index and S-phase estimates from DNA histograms was poorer in biopsy specimens collected during therapy than in pretreatment specimens.

Antineoplastic Agents↗
PubMed2005

Randomized controlled trial to evaluate radiotherapy +/- endocrine therapy versus endocrine therapy alone for PSA failure after radical prostatectomy: Japan Clinical Oncology Group Study JCOG 0401.

A randomized controlled trial has started in Japan to evaluate radiotherapy and endocrine therapy for prostate-specific antigen (PSA) failure after radical prostatectomy. Patients who have PSA failure after radical prostatectomy for localized prostate cancer (T1-2N0M0) are randomized into treatment groups of either radiotherapy +/- endocrine therapy or endocrine therapy alone. The Urologic Oncology Study Group (UOSG) in the Japan Clinical Oncology Group (JCOG) composed of 36 specialized institutions will recruit 200 patients. The primary end-point is time to treatment failure (TTF) of bicalutamide, and secondary end-points are TTF of protocol treatment, progression-free survival, overall survival, adverse events and quality of life (QOL). The Clinical Trial Review Committee of the JCOG approved the protocol on April 13, 2004, and the study was activated on May 17, 2004.

Adult↗
PubMed1989

The use of endocrine therapy.

Endocrine therapy is still a mainstay in the treatment of metastatic breast cancer. It has been observed that about one third of women with metastatic breast cancer will respond to endocrine therapy. This response rate is surprisingly consistent for a wide variety of endocrine approaches, with a few exceptions, such as the use of corticosteroids, androgens, or danazol for which the response rate appears lower. Endocrine therapy is, in general, considerably less toxic than single or combination chemotherapy, but toxicities within the endocrine therapies may vary considerably. Thus, the choice and optimal sequencing of endocrine maneuvers relate largely to minimizing toxicity and optimizing total duration of benefit. A number of newer endocrine approaches including the antiestrogens and aminoglutethimide have recently provided a variety of less toxic choices. Even more recently, compounds such as the LHRH agonists and antiandrogens are being tested, although their use remains experimental. Combinations of two or more endocrine therapies or of chemotherapy and endocrine therapy are currently, also a subject of considerable interest. No studies to date, however, have shown a clear advantage to concurrent chemotherapy endocrine combinations or to the use of two or more concurrent hormonal maneuvers, with the possible exception of the combination of prednisolone with tamoxifen or with oophorectomy, which has improved overall survival in two trials.

Adrenalectomy↗
PubMed2004

Adjuvant endocrine therapy.

Endocrine therapy remains a cornerstone of systemic therapy for breast cancer even though it was first introduced more than a century ago. In the past three decades a large number of randomized trials involving several tens of thousands of patients have been performed to determine the role of endocrine therapy in the adjuvant setting. The results of these studies indicate that hormonal therapy should be considered the standard adjuvant systemic treatment for the majority of patients with invasive breast cancer irrespective of age, menopausal status or tumour stage. This chapter aims to describe the "state of the art" relative to the use of adjuvant endocrine therapy with special focus on a number of salient issues, including: (i) the role of ovarian ablation and luteinising hormone releasing hormone (LHRH) analogues among pre-menopausal patients; (ii) optimal duration of tamoxifen; (iii) adjuvant therapy with third-generation, selective aromatase inhibitors; (iv) predictive biomarkers; (v) side-effects; (vi) combination endocrine therapy; (vii) future development of endocrine therapy.

Antineoplastic Agents, Hormonal↗
PubMed2001

Androgen receptor mutations in carcinoma of the prostate: significance for endocrine therapy.

Endocrine therapy for advanced prostate cancer involves androgen ablation (orchiectomy or application of luteinizing hormone releasing hormone analogs) and/or blockade of the androgen receptor (AR) with either steroidal (cyproterone acetate) or nonsteroidal (hydroxyflutamide, bicalutamide and nilutamide) antiandrogens. These antagonists prevent androgen-induced conformational change and activation of the AR. During long term androgen ablation, the AR adapts to an environment with low androgen concentrations and becomes hypersensitive to low concentrations of androgens, either alone or in combination with various cellular regulators. Bicalutamide can switch from antagonist to agonist during long-term androgen withdrawal, as shown in prostate cancer LNCaP cells. AR point mutations were detected in metastatic lesions from human prostate cancer more frequently than in primary tumors. Although functional characterization of only some mutant AR detected in prostate cancer tissue has been performed, data available suggest that they are activated by dihydrotestosterone, its precursors and metabolites, synthetic androgens, estrogenic and progestagenic steroids and hydroxyflutamide. A direct association between AR mutations and endocrine withdrawal syndrome has been investigated in only one study thus far. There is no evidence at present that activation of any of the mutant AR genes detected in prostate cancer is enhanced in the presence of a nonsteroidal AR stimulator. Coactivators of the AR are proteins that associate with the receptor, possess histone acetylase activity and facilitate AR activation. The coregulatory proteins ARA70 and ARA160 differentially affected the activity of the mutated AR Glu(231)-->Gly, which was discovered in a mouse authochthonous prostate tumor. ARA70 enhanced receptor activation by both androgen and estradiol, whereas ARA160 augmented only androgen-induced AR activity. Novel experimental therapies that down-regulate AR expression have been developed; they include the application of ribozymes and antisense oligonucleotides.

Androgen Antagonists↗
PubMed2005

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer.

PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months. CONCLUSIONS: The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.

Adenocarcinoma↗
PubMed1998

Different survival determinants of metastatic breast cancer patients treated with endocrine therapy or chemo-endocrine therapy.

Female patients (n=371) with metastatic breast cancer were treated with endocrine or chemoendocrine therapy as the first-line treatment. Clinical prognostic factors for response and survival were compared between the treatments, including age of the patients, menopausal status, estrogen receptor (ER), disease-free interval (DFI), dominant site of metastasis, number of metastatic organs, performance status (PS), and prior therapy. Although a significantly higher response rate was obtained by the chemo-endocrine therapy compared with the endocrine therapy, the median survival time of patients in endocrine therapy was much longer than those in chemo-endocrine therapy. Multivariate analyses with the logistic regression model showed that in women treated with endocrine therapy ER was shown to be the sole determinant for response, while PS and dominant site of metastasis were selected to be influential in chemotherapy group. For overall survival, the Cox proportional hazard model analysis showed that by endocrine therapy, ER and dominant site were significant determinants of survival, but that of chemotherapy the survival was determined by PS, dominant site, and age of the patients. When response to therapy was included in the Cox survival analysis at the time of 3-month after therapy in the landmark method, the response was the most important factor for survival in both treatment groups, however dominant site in endocrine therapy, and dominant site, PS, and age in chemo-endocrine therapy significantly modified survival. It is concluded that endocrine therapy and chemo-endocrine therapy have different determinants for response and survival in metastatic breast cancer, and that in the survival analysis treatment modality should be included as a prognostic factor.

Adult↗
PubMed1991

Modal DNA-values in prostate cancer patients with deferred therapy or endocrine therapy.

Modal DNA-values were assessed with flow cytometry in 269 patients with newly detected untreated prostate cancer. One hundred and seventy-two patients with low-grade, low-stage, non-metastasized cancers were followed without treatment and in this group initial tumor ploidy had no prognostic value. Ninety-seven patients with clinically more advanced prostate cancers were subjected to endocrine therapy and in this group ploidy was prognostic regarding cancer-related survival.

Adult↗
PubMed1990

[A randomized trial of endocrine therapy, chemotherapy, and chemo-endocrine therapy in advanced breast cancer].

A randomized trial of endocrine therapy (adreno-oophorectomy, H), chemotherapy (FAC, C), chemoendocrine therapy (FAC + tamoxifen, H'C, or FAC + adreno-oophorectomy, HC) was performed in 114 advanced breast cancer patients from September, 1979 to December, 1983, and 106 were evaluable. The response to H, C, H'C, and HC was shown to be 33% (10/30), 54% (14/26), 59% (17/29), and 76% (16/21), respectively. There was a significantly higher response rate in HC group than H group. Higher but not significantly different response was obtained by H'C as compared with H. There were no significant differences in the overall survival among the treatment arms. However, patients treated with H survived longer (greater than 5 years). These results suggest that higher response obtained by chemotherapy, alone or in combination with endocrine therapy does not seem to contribute to the prolongation of survival of the patients.

Adrenalectomy↗
PubMed2006

A randomized trial comparing radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy for locally advanced prostate cancer: results at median follow-up of 102 months.

BACKGROUND: To investigate the optimal treatment of locally advanced prostate cancer, a prospective randomized trial was conducted to compare radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy. METHODS: One hundred patients with T2b-3N0M0 prostate cancer were enrolled and 95 were evaluated. Of 95 cases, 46 underwent radical prostatectomy with pelvic lymph node dissection and 49 were treated with external beam radiation by linear accelerator with 40-50 Gy to the whole pelvis and 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiotherapy and continued thereafter. The long-term outcome and morbidity were examined. RESULTS: Median follow-up period was 102 months. At 10 years overall survival rates in the surgery group were better than the radiation group (76.2% versus 71.1% for biochemical progression-free rates; P=0.25, 83.5% versus 66.1% for clinical progression-free rates; P=0.14, 85.7% versus 77.1% for cause-specific survival rates; P=0.06, and 67.9% versus 60.9% for overall survival rates; P=0.30), although none of them reached statistical significance. Erectile dysfunction was recognized in almost all patients as a result of continuous endocrine therapy. Incontinence requiring more than one pad per day was observed more frequently in the surgery group than the radiation group (P<0.01). CONCLUSIONS: For the treatment of patients with locally advanced prostate cancer, when combined with endocrine therapy, either radical prostatectomy or external beam radiotherapy demonstrated favorable long-term outcomes. The radiation dose of 60-70 Gy might not be enough for the local treatment of locally advanced prostate cancer.

Adenocarcinoma↗
PubMed1990

[Clinical studies on endocrine therapy of prostatic carcinoma (2): Prognosis of patients with prostatic carcinoma given endocrine therapy, and analyses of causes of death and side effects of endocrine therapy].

Of 572 patients with prostatic carcinoma, 497 received endocrine therapy as the initial treatment. These patients were surveyed in a cooperative research study by members from five universities. Prognosis, causes of death and side effects of estrogen therapy were studied. The prognosis of patients who had received endocrine therapy became worse, as the stage progressed. The prognosis of those who had received a combination of estrogen therapy with castration tended to be better than that of those who had received estrogen therapy alone. Similarly, the prognosis of those who had received a combination of progesterone therapy with castration tended to be better than that of those who had had progesterone therapy alone. No relationship was found between estrogen doses (low, medium and high) and prognosis, although a precise comparison among the three could not be made because of the smaller number of patents with low doses. A high dose of estrogen may not always be the indication, rather a medium dose such as 300 mg diethylstilbestrol diphosphate may be clinically appropriate. The cause of death could be identified in 303 patients who had received endocrine therapy. Cancer-related death was the most frequent (63.7%), and cardio- or cerebrovascular death accounted for only 14.2% of the cases. When this analysis was confined to the patients who had received estrogen therapy, estrogen administration seemed to be the cause of cardio- or cerebrovascular death of 16.1% of the patients. Daily dosing of estrogen was not definitely related to the incidence, or the interval to cardio- or cerebrovascular death. However, among the patients who had died of cardio- or cerebrovascular disease, 50% of the patients who had received a medium or high dose of estrogen tended to die within two years after treatment, while 50% of those who had received a low dose died within three years.

Cause of Death↗
PubMed1998

The primary use of endocrine therapies.

Primary endocrine therapy is potentially superior to primary chemotherapy in patients with ER-positive tumors. The ability to give endocrine therapy perioperatively may be a better test than chemotherapy of the hypothesis that the events accompanying surgery affect prognosis. However, a major problem in all studies of primary endocrine therapy is that there has been no clear experimental test of preoperative versus postoperative therapy. This is because the major thrust of treatment has been in the elderly with the purpose of determining whether surgery can be avoided altogether. The fact that in ER-positive tumors primary endocrine therapy is associated with similar response rates to chemotherapy make it an attractive therapy for older women. This is the group where adjuvant chemotherapy has not been adequately tested (> or = 70 years of age). In contradistinction, adjuvant endocrine therapy shows marked survival benefits in patients with ER-positive tumors in these age groups (Table 1). It appears likely that primary endocrine therapy will allow breast conservation and prognostic information as is seen with chemotherapy. A major question which requires answering is whether primary endocrine therapy will improve survival more than adjuvant therapy alone. Although ER status is a good marker of responsiveness, its specificity, in particular, is not optimal. The ability to assess the dynamic effects of primary endocrine therapy by sequential biopsy and measurement of biological responses to oestrogen deprivation may allow us to predict precisely the patients likely to benefit from treatment. This clinical scenario allows us to use other potentially useful assessments such as the non-invasive estimation of angiogenesis using quantitative imaging techniques of blood flow. The newer anti-estrogens and aromatase inhibitors appear ideally suited to primary therapy since they have rapid and profound inhibitory activities, few or no agonist effects, and low side effect profiles. A preoperative trial of Faslodex is planned by the EORTC and another with Arimidex is under consideration by the ATAC (Arimidex, tamoxifen and combined) Trialist Group (Fig. 7). The precise design of these studies will require considerable thought.

Aged↗
PubMed1990

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

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

Antineoplastic Agents↗
PubMed1997

Early endocrine therapy versus radical prostatectomy combined with early endocrine therapy for stage D1 prostate cancer.

OBJECTIVE: To compare disease progression and survival of patients with stage D1 adenocarcinoma after treatment with either early androgen ablation alone or combined with radical prostatectomy. PATIENTS AND METHODS: A retrospective non-randomized study was performed in a series of 76 consecutive patients who underwent pelvic lymphadenectomy and had pathological stage D1 (T1-3, pN1-2, MO) prostate cancer; 37 patients underwent early endocrine therapy (EET) and 39 underwent radical prostatectomy with immediate adjuvant endocrine therapy (combined therapy, COM). The median follow-up was 3.8 years (range 0.26-13). The patients were statistically homogeneous for tumour grade, local tumour stage and nodal involvement, but not for age at lymphadenectomy (67 years and 62 years, respectively, P = 0.019, a confounding factor in favour of COM). RESULTS: Twelve patients (32%) in the EET group and 11 (28%) in the COM group died: the Kaplan-Meier actuarial overall survival curves showed no statistically significant difference between the treatment groups, but there was a trend in favour of the COM group. There was also no significant difference in the cause-specific survival. In the EET group, 17 men (46 %) had local (five of 37, 14%) or systemic (13 of 37, 35%) progression and in the COM group 23 patients (59%) had local (eight of 39, 21%) or systemic (20 of 39, 51%) progression. Four patients had an elevated level of prostate specific antigen with no clinical recurrence. Transurethral resection of the prostate was necessary for three (8%) patients in the EET group and for two (5%) of those receiving COM. The Kaplan-Meier actuarial disease-free survival curves were not significantly different. Similar results were obtained when the 25 patients with early-stage (T1 and T2) and the 51 patients with advanced primary tumours (T3 and T4) were analysed separately. CONCLUSION: These results suggest that in patients with stage D1 prostate cancer, radical prostatectomy combined with adjuvant endocrine therapy offers no advantage over endocrine therapy alone, neither for curative nor palliative intent.

Adenocarcinoma↗
PubMed1991

[Clinical studies on endocrine therapy for prostatic carcinoma (4): Initial response to endocrine therapy and prognosis].

We have already pointed out by the use of multivariate analysis that local response of the prostate is one of the important prognostic factors in patients receiving endocrine therapy. Herein, we investigated how the local response to endocrine therapy affects the survival rate or the survival period. We also studied the relationship between the local response and histopathological findings. The local response of prostate was not correlated with the stage progression. Sixty-seven percent of the patents in each stage had an initially favorable local response of the prostate, in which the primary tumor became flattened or reduced by endocrine therapy. By contrast, the local response of the prostate was well correlated with the prognosis in each stage. Patients with a flattened or reduced primary lesion following endocrine therapy showed a higher survival rate or a longer survival period than those with the unchanged lesion. This result has confirmed that the local response of prostate to endocrine therapy is useful in predicting clinical courses of patients. Grade of structural atypism (SAT), one of the pathological findings, had a correlation with local response of the prostate. With an elevation of the SAT grade, the proportion of patients with unchanged primary lesion was increased.

Humans↗