Long-term Hormone Therapy Research Articles

Early results of localised, high-risk prostate cancer treated by moderate hypo-fractionation (70 Gy at 2·5 Gy per fraction): 5-year experiences of a moderate hypo-fractionation regimen

AbstractBackground:Radiotherapy is one of the treatments used to treat prostate cancer, and dose escalation to 74–78 Gy in conventional fractionation is the standard regimen. Currently, according to the hypothesis of low alpha/beta ratio in prostate cancer cells, using hypo-fractionation has been reported in many publications with promising results. This retrospective study was designed to evaluate the implementation of a moderate hypo-fractionation regimen in high-risk prostate cancer in our division.Materials and Methods:Between 2012 and 2017, 40 patients with high-risk, localised prostate cancer were treated by a moderate hypo-fractionation regimen (70 Gy at 2·5 Gy per fraction) with intensity-modulated radiation therapy. The data related to treatment outcomes and toxicities were evaluated.Results:The mean PSA at diagnosis was 86·2 ng/mL (95% CI 49·9–122·4). Thirty-eight patients received long-term hormonal therapy. Fifty-two percent had a Gleason score of 8–10, and 65% had an initial PSA >20 ng/mL. The mean doses (in EQD2) to the D50% of PTV, D2% of organs at risk (bladder, rectum and bowels) were 80, 78·3, 76·4, and 50·2 Gy, respectively. Two patients had biochemical recurrence during the follow-up period.Conclusion:A moderate hypo-fractionation regimen (70 Gy at 2·5 Gy per fraction) is feasible. Our experience found that this regimen yields tolerable, acceptable toxicity profiles in high-risk, localised prostate cancer patients.

A right atrium metastasis of breast cancer after long-term endocrine therapy

We report a case of right atrial metastasis in a 66-year-old female patient with breast cancer. The patient presented with palpitation and dyspnea after long-term endocrine therapy. A large echo-dense mass was found in the right atrium after the examination. In order to relieve the symptoms, the patient underwent a resection of the atrial lesion, and the pathology confirmed that it was metastatic breast cancer. Next-generation sequencing (NGS) of the entire exon was taken to explore the gene expression of the metastatic lesion. Forty-eighty genes were identified with mutations, and the mutations of ATM and ESR1 were considered to be associated with the development and metastasis of breast cancer in this case.

P3460Structural and functional changes of vascular wall in women of perimenopausal period with long-term menopausal hormone therapy

Abstract Introduction Features of changes in the vascular wall in women of the menopausal period are not sufficiently illuminated. Most of the studies evaluating the effect of menopausal hormonal therapy (MHT) on the structural and functional state of the vascular wall were limited to the time frame from several months to 1–3 years, which distinguishes them from our study. Purpose To evaluate structural and functional changes in the vascular wall in women of early postmenopausal period with prolonged use of low doses of MHT 1 mg of 17β-estradiol (E2) and 2 mg drospirenone (DRSP). Methods The study included 162 women in the early postmenopausal period with climacteric syndrome were divided into 2 groups: the main group of 84 women assigned MHT 1 mg E2 /2 mg DRSP, control group of 78 women who did not receive MHT. Duration of follow-up 5,2 (4,8; 5,7) years. Explored pulse wave velocity (PWV). Bbrachial blood pressure was measured non-invasively over the 24 h with an electronic, oscillometric, automated device (BPLab) with the assessment of 24-h central arterial pressure (CAP), aortic augmentation index (AIx), arterial stiffness index (ASI); ambulatory arterial stiffness index (AASI). Endothelium-dependent vasodilation (EDV) of the brachial artery was evaluated. Results In women of the main group PWV made up 7.19±1.7 m/s initial and 7.53±1.3 m/s to the end of the study (p>0.05); in the control group - 7,21±1.8 m/s and 7.95±1.9 m/s (p<0.001). In the women of the main group by the end of the study a decrease in the CAP was noted from 38.4±6.2 to 35.3±4.1 mm Hg. (p<0.001), in the women of the control group there were no changes of 41.4±9.6 and 40.9±9.8 mm Hg. (p<0.001 between women of both groups at the end of the study). In women of the control group, a significant increase in AIx was found from 31.0 (20.0; 35.0)% initially to 33.0 (29.0; 37.0)% by the end of the study (p<0.05) and no changes in women of the main group – 27.0 (20.0; 35.0)% and 28.0 (20.0; 33.0)%. Multidirectional changes ASI were revealed: a decrease in women of the main group from 132.0 (121.0; 142.0) to 127.0 (115.5; 137.0) cu and an increase from 133.0 (111.0; 155.0) to 148.0 (134.2; 171.0) cu in women of the control group (p<0.01 between women of both groups at the end of the study). By the end of the study, there was a decrease in AASI in women of the main group from 0.379 (0.320; 0.463) to 0.264 (0.203; 0.329) cu (p<0.001) and the absence of changes AASI value in women of the control group – 0.360 (0.283; 0.471) and 0.370 (0.310; 0.476) cu. In women of the main group, an increase in the brachial artery EDV was found from 8.6±7.4% initially to 11.1±6.8% by the end of the study (p<0.05) and no change in women in the control group −7.3±5.6% and 6.2±5.0%. Conclusion In women in early postmenopause with prolonged MHT of 1 mg E2/2 mg DRSP positive changes in the structural and functional state of the vascular wall were established.

Effects of Estrogen on Spermatogenesis in Transgender Women

ObjectiveTo characterize spermatogenesis in the estrogenized transgender patient. Materials and MethodsThis is a retrospective, single-center, cross-sectional study. Seventy-two transgender women underwent gender-affirming orchiectomy between May 2015 and January 2017. All were on long-term (>1 year) cross-sex hormonal therapy prior to orchiectomy. Patient data were obtained via chart review. Histologic analysis was performed by a pathology resident under the supervision of a genitourinary pathologist. The main outcome is histologic presence of germ cells and presence of spermatids (a proxy for preserved spermatogenesis) in orchiectomy specimens. ResultsThere were 141 pathologic specimens available for analysis. Germ cells were present in 114 out of 141 (81%) testicles. Spermatids were present in 57 (40%) testicles. Presence of germ cells was associated with older age (43 vs 35 years, P = .007) and increased testicular weight (28.6 g vs 19.3 g, P <.001). Presence of spermatids was associated with increased weight (31.5 g vs 23.3 g, P <.001) and volume (20.3 mL vs 12.6 mL, P <.001). There was a linear correlation between testis volume and preserved spermatogenesis (Pearson's r = 0.448, P <.001). ConclusionDespite long-term hormone therapy, the majority (80%) of transgender women have germ cells present in the testicle. Spermatogenesis is preserved in approximately 40% of these individuals. Duration of hormonal therapy did not affect the degree of preservation of germ cells or spermatogenesis but starting hormonal treatment at a younger age may be associated with decreased germ cells in the testicle. Volume of testicles predict presence of preserved spermatogenesis.

Risk of developing gestational diabetes in women after assisted reproductive technologies

Hypothesis/aims of study. Gestational diabetes mellitus (GDM) is one of the leading causes of perinatal morbidity and mortality. The use of assisted reproductive technologies (ART) is an independent risk factor for the development of GDM. Among other risk factors are overweight, diabetes burdened heredity, previous GDM, previous birth weight more than 4 kgs, stillbirth, miscarriage in history, glucosuria, polyhydramnios in this pregnancy, age over 30 years, polycystic ovary syndrome. The most significant risk factor for GDM is excess weight before pregnancy. The aim of this study was to investigate the risks of GDM in patients after ART.&#x0D; Study design, materials, and methods. 342 case histories of women with single pregnancy for the period 2014–2017 were studied on archival material. The main group consisted of 234 women with single pregnancy after ART. The comparison group comprised 108 medical records of fertile women with a history of single pregnancy that occurred spontaneously. The exclusion criteria in the comparison group were pregestational diabetes mellitus and severe extragenital pathology.&#x0D; Results. The incidence of GDM was significantly higher in the group of women in whom pregnancy occurred after ART compared to the comparison group (15.4 ± 0.4% and 5.5 ± 0.4% respectively). In the main group, patients were more likely to have overweight, extragenital pathology and pregnancy complications.&#x0D; Conclusion. The increase in the frequency of GDM among patients after ART is probably associated with late reproductive age, initially negative somatic background at the time of entry into the IVF protocols, as well as long-term hormone therapy during pregnancies after ART, starting from early terms.

Long-Term Drug Therapy and Drug Discontinuations and Holidays for Osteoporosis Fracture Prevention: A Systematic Review.

Optimal long-term osteoporosis drug treatment (ODT) is uncertain. To summarize the effects of long-term ODT and ODT discontinuation and holidays. Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies. 48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB). Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy. Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE). No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays. Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms. National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

MON-LB040 Correlation Between Length of Hormone Therapy and Adverse Events in Transgender Veterans

Objectives: We studied the transgender veteran population at a Veteran Affairs Medical Center (VAMC) retrospectively, regarding whether there is a correlation between length of hormone therapy, age and incidence of adverse events. Introduction: To date there is limited published data about long-term hormone therapy use in transgender individuals and specifically no published data for average age over 41 years. It is known from sex hormone-based studies in cis-gender individuals that long term use carries risks of adverse events including increased cardiovascular events, breast cancer, and thromboembolic events. Recent data does suggest that particularly with transgender women hormone replacement therapy increases risk of venous thromboembolism. Methods: We performed a retrospective chart review on any individual who identified by ICD 9 or 10 code with gender identity disorder, gender dysphoria, transgender female, or transgender male within the VAMC over the past 10 years. These charts were assessed for hormone therapy prescriptions specifically: estrogen, testosterone, spironolactone, or leuprolide, as well as history of such prescription. Clinic notes were reviewed regarding adverse events related to hormone therapy. Results: Eighty-seven patients were found with the ICD codes. Of those, 78 (89.7%) have previously been prescribed or are currently prescribed hormone therapy. Of all chart reviews, 8 (9.2%) suffered adverse events including venous thromboembolism, myocardial infarction, elevated hematocrit, elevated prolactin, and hyperkalemia. Of these adverse events 5 (5.7%) were secondary to estrogen, 2 (2.3%) were secondary to testosterone, and 1 (1.1%) was secondary to spironolactone. Interestingly, only 5 (5.7%) were symptomatic (venous thromboembolism, myocardial infarction, hyperkalemia) while 3 (3.4%) were asymptomatic (elevated hematocrit, elevated prolactin). The average age of adverse event was 57.7 years old and average time on hormone therapy until adverse event was 3.2 years. Five (62.5%) adverse events occurred at or before 3 years on hormone therapy and 2 of the 3 remaining adverse events that occurred after 3 years were asymptomatic as above. Conclusions: Among transgender patients at a VAMC 9.2% were identified as suffering an adverse event secondary to hormone therapy at an average at of 57.7 years old with an average length of time on hormone therapy to adverse event of 3.2 years. Despite our small sample size there appears to be a trend of symptomatic adverse events including venous thromboembolism, myocardial infarction, and hyperkalemia that occur at or before 3 years of hormone therapy.

Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy: Results from a Multi-Institutional Study

BackgroundThe optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. ObjectiveTo test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. Design, setting, and participantsThe study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1ng/ml at 1mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. Outcome measurements and statistical analysisThe outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). Results and limitationsOverall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9mo. At median follow-up of 93mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p=0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p=0.001; 0 vs ≥2, p<0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration. ConclusionsThe oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT. Patient summaryWe tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT.

ER+/HER2+ Breast Cancer Has Different Metastatic Patterns and Better Survival Than ER−/HER2+ Breast Cancer

BackgroundHuman epidermal growth factor receptor 2–positive (HER2+) breast cancer is generally treated with HER2-targeted therapy combined with chemotherapy. Patients with HER2+ and estrogen receptor–positive (ER+) cancer are additionally treated with long-term hormone therapy. This study examined the metastatic pattern and prognosis of both ER+/HER2+ and ER−/HER2+ breast cancer. Patients and MethodsA total of 54,147 patients with HER2+ breast cancer from the National Cancer Data Base (NCDB, 2010-2013) and 31,946 patients with HER2+ breast cancer from the Surveillance, Epidemiology, and End Results Program (SEER, 2010-2014) were examined. Sites of metastasis and overall survival (OS) were examined in the NCDB, while OS and breast cancer–specific survival were examined in the SEER database. ResultsCompared to ER−/HER2+ breast cancer, ER+/HER2+ breast cancer was more likely to metastasize to bone but less likely to brain, liver, and lung and less likely to result in multiple metastases. In univariate analysis based on the NCDB, patients with ER−/HER2+ breast cancer had worse OS in all metastasis subsets, including patients who received HER2-targeted therapy. This poor survival for ER−/HER2+ persisted in patients with metastasis to bone and lung, and multiple metastases. In multivariate analysis adjusting for age, tumor grade, surgery, chemotherapy, HER2-targeted therapy, and hormone therapy, ER−/HER2+ patients with bone metastasis still had worse OS. In the SEER, ER−/HER2+ patients had both worse OS and breast cancer–specific survival in univariate analysis. ConclusionThis large study showed patients with ER+/HER2+ and ER−/HER2+ breast cancers had different metastatic patterns. Patients with ER−/HER2+ breast cancer may require more aggressive treatment.

HEALTH-RELATED QUALITY OF LIFE IN EARLY BREAST CANCER PATIENTS WITH HORMONE RESPONSIVE

Objective: The management of early breast cancer (EBC) is performed with a series of treatments consisting of surgery and systemic therapy, along with long-term endocrine therapy for hormone responsive. The treatment generates a high illness effect that will affect the life quality of EBC patients. The objective of this study was to measure EBC patients’ quality of life after undergoing the treatment.Methods: A cross-sectional study was conducted by interviewing EBC patients using EQ-5D-5L instrument at private hospitals in Yogyakarta and Semarang, Indonesia. The EBC patients were women aged 18-60 y who had undergone surgery in 2010-2013 and received endocrine therapy.Results: Of the 71 patients identified, 45 patients were in disease-free survival (DFS) state, 8 patients were in locoregional recurrence (LR), and 18 patients were in metastasis (M) state. Mobility and self-care problems occurred in patients who had metastasis (4.23%). The problem of usual activities occured in patients who had recurrence (22.54%). Most of the patients (84.51%) had pain problem, and all patients had an anxiety problem. The mean utility score (SD) in DFS patients was 0.841 (0.052), in LR patients was 0.758 (0.092), and in patients who had metastasis was 0.653 (0.104). The mean scores of EQ-5D VAS (SD) for EBC patients in DFS, LR and M health state were 86.56 (6.29), 81.88 (5.30), and 69.17 (5.75), respectively.Conclusion: The health states of EBC significantly affect HRQOL of patients. Efforts should be made to improve the quality of life of EBC patients especially in terms of pain and anxiety reduction.

Insights from outside BJOG

Insights from outside BJOG

Is Monitoring Mean Platelet Volume Necessary in Breast Cancer Patients?

BackgroundMean platelet volume (MPV) is a parameter that increases during thrombotic and cardiovascular events. Tamoxifen (Tmx) and aromatase inhibitors (AIs), which are adjuvant endocrine therapies, may cause serious side effects, such as vascular thrombosis. The present study investigated the changes in MPV values of breast cancer patients receiving long-term adjuvant hormone therapy and the relationship of MPV with adverse effects of hormonotherapy.MethodsData of 261 patients who had pathologically confirmed estrogen or progesterone receptor positive invasive breast cancer and had received hormonotherapy for at least a 5-year period were retrospectively analyzed. MPV levels were measured at baseline and at the first and fifth year of hormone therapy.ResultsAll patients were females and their median age was 50 years (range, 27–78 years). The mean MPV value was significantly increased in all patients in the Tmx, AI, and switch groups over time (p<0.001).ConclusionThis is the first study evaluating the relationship between the 5-year adjuvant endocrine therapy and changes in MPV values in breast cancer patients. Monitoring changes in MPV values may be predictive for severe side effects in breast cancer patients receiving hormone therapy.

Improving Access and Adherence to Endocrine Therapy With Nurse-Based Intervention

Purpose The majority of women with breast cancer from low-income countries, including Ethiopia, present with advanced clinical stage disease, which results in limited and difficult therapeutic options and high mortality rates. In Ethiopia, breast cancer is the most common cancer. We found that 70% of breast cancer cases in Ethiopia are hormone receptor positive. Endocrine therapy is one of the treatment options recommended for breast cancer but that is highly underutilized in the country. Recommendations on interventions to improve uptake and adherence to therapy exist, but studies that have assessed the feasibility of implementing these are limited. Our study (n = 107) in rural Ethiopia revealed an estimated 53% 2-year survival rate in patients who underwent surgery only. In our pilot study, of 51 eligible patients 26 initiated therapy and one half of those adhered after 1 year. Our study aims to evaluate the effectiveness of using a trained breast nurse navigator to improve patient adherence to tamoxifen therapy among patients with breast cancer in rural Ethiopia. Methods A cluster randomized intervention trial is being carried out in rural hospitals in southwestern Ethiopia from February 2018 to June 2019. We use hospitals in clusters as the units of randomization. The sample size includes four per intervention arm and control arm, with each cluster comprised of approximately 15 patients. Before intervention, all patients in the hospitals will receive tamoxifen therapy free of charge. Hormone receptor status of the breast cancer specimen will be determined before the initiation of therapy or throughout the course of therapy. The primary outcome of this trial is adherence to endocrine therapy on the basis of objective and subjective measures. Data will be collected with a prospective repeated measures approach. Analysis will be based on an intention-to-treat principle. Results The trial aims to provide evidence on the effectiveness of the breast nurse intervention to improve adherence to long-term endocrine therapy and answer the following research question: does the nursing intervention improve long-term treatment adherence by patients to endocrine therapy compared with those who receive usual care services? Conclusion These data are essential to maximize the impact of trained nurse-based interventions on adherence to endocrine (tamoxifen) therapy among patients with breast cancer on follow-up. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Eva J. Kantelhardt Travel, Accommodations, Expenses: Daiichi Sankyo Oncology Europe

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness

BackgroundResults from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources. ObjectiveTo assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting. Design, setting, and participantsWe modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. InterventionSOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75mg/m2) was administered alongside SOC for six three-weekly cycles. Outcome measurements and statistical analysisThe model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results and limitationsThe model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled. ConclusionsDocetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. Patient summaryStarting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.

P1576The influence of long-term hormone therapy for advanced prostate cancer on the ventricular repolarization and global longitudinal strain

P1576The influence of long-term hormone therapy for advanced prostate cancer on the ventricular repolarization and global longitudinal strain

Evaluation of Efficacy of Long-term Growth Hormone Therapy in Patients with Hypochondroplasia

Hypochondroplasia is a cause of disproportionate short stature and characterized by minor clinical manifestations. The aim of this study was to evaluate the efficacy of long-term growth hormone (GH) therapy in hypochondroplastic cases with inadequate response to GH stimulation tests. In this study, six patients who had a height standard deviation score of -3.43 before the treatment and a mean age of 7.42 years and who had received GH treatment at a dose of 0.2 mg/kg/week for a mean period of 4.45 years were evaluated. A good response was found in the first year of treatment, but this increase was not found to be sufficient for the patients to achieve an adequate final height.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol

BackgroundAdding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP versus SOC+DocP. MethodRecruitment to SOC+DocP and SOC+AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for≥2years and RT to the primary tumour. Stratified randomisation allocated pts 2:1:2 to SOC; SOC+docetaxel 75mg/m2 3-weekly×6+prednisolone 10mg daily; or SOC+abiraterone acetate 1000mg+prednisolone 5mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC+AAP, and HR>1 favours SOC+DocP. ResultsA total of 566 consenting patients were contemporaneously randomised: 189 SOC+DocP and 377 SOC+AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8–10; 449 (79%) WHO performance status 0; median age 66years and median PSA 56ng/ml. With median follow-up 4years, 149 deaths were reported. For overall survival, HR=1.16 (95% CI 0.82–1.65); failure-free survival HR=0.51 (95% CI 0.39–0.67); progression-free survival HR=0.65 (95% CI 0.48–0.88); metastasis-free survival HR=0.77 (95% CI 0.57–1.03); prostate cancer-specific survival HR=1.02 (0.70–1.49); and symptomatic skeletal events HR=0.83 (95% CI 0.55–1.25). In the safety population, the proportion reporting≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC+DocP, and 40%, 7% and 1% SOC+AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. ConclusionsThis direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registrationClinicaltrials.gov: NCT00268476.

Addition of docetaxel to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Long-term survival, quality-adjusted survival, and cost-effectiveness analysis.

162 Background: Results from large randomised controlled trials have shown that adding docetaxel to standard of care (SOC) in men initiating hormone therapy for prostate cancer prolongs survival for those with metastatic disease and prolongs time to treatment failure for those without metastatic disease. We report on the impact of docetaxel on health related quality of life (HRQoL), resource use and cost-effectiveness for men treated in the STAMPEDE trial. Methods: Health outcomes and costs in the UK NHS were modelled using EuroQol (EQ-5D)and resource use data collected within the STAMPEDE trial (STAMPEDE enrolled men advanced prostate cancer starting first line hormone therapy. SOC was hormone therapy for ≥2 years and radiotherapy in some patients. Docetaxel (75 mg/m2) was administered alongside SOC for six 3-weekly cycles with prednisolone 10 mg daily. Lifetime predictions of costs, changes in predicted survival duration, quality adjusted life years (QALYs), and incremental cost effectiveness ratios (ICERs) were calculated. Results: Compared to patients allocated SOC, docetaxel was estimated to extend predicted survival by an average of 0.89 years for M1 patients and 0.78 years for M0 patients. Docetaxel was estimated to extend discounted QALYs by 0.51 years in M1 patients and 0.39 years in M0 patients. QALY gains in M0 patients were driven by the beneficial effect of delayed and reduced relapse. Docetaxel was cost-effective both in M1 patients (ICER = £5,514/QALY vs. SOC) and M0 patients (higher QALYs, lower costs vs. SOC). The probabilistic sensitivity analysis indicated a very high probability ( &gt; 99%) that docetaxel is cost-effective in both M0 and M1 patients. Docetaxel remained cost effective in M0 patients even when no survival advantage was assumed due to reductions and delays in relapse. Conclusions: Docetaxel improves overall HRQoL, delays time to, and reduces the need for, subsequent therapy, and is cost-effective, amongst patients with both non-metastatic and metastatic disease. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in non-metastatic patients. Clinical trial information: ISRCTN78818544.

Operation, hormone therapy and recovery of the patients with severe forms of adenomyosis

Endometriosis is among the prevalent gynecological diseases and diagnosed in 10% of women of reproductive age. Endometriosis/adenomyosis is becoming increasingly a health-social problem, which is associated with severe clinical manifestations and recurrent disease which has a negative effect on quality of life, women ability to work and her reproductive function. This article presents modern approaches of drug therapy to treat severe forms of adenomyosis. We have reviewed recent major studies in the field of surgical treatment of this disease, analyzed the main stages of disease progress and the results of our surgeries. Here, we are presenting our own results of long-term post-operative hormonal therapy and complex medical treatment.

Exploring the Pharmacological Mechanism of Danzhi Xiaoyao Powder on ER‐Positive Breast Cancer by a Network Pharmacology Approach

Background Breast cancer is the most common malignancy among women worldwide, but the long-term endocrine therapy is frequently associated with adverse side effects. Danzhi Xiaoyao powder (DXP) is a herbal formula that has an effect on breast cancer, especially ER-positive breast cancer. However, the active compounds, potential targets, and pharmacological and molecular mechanism of its action against cancer remain unclear. Methods A network pharmacology approach comprising drug-likeness evaluation, oral bioavailability prediction, Caco-2 permeability prediction, multiple compound target prediction, multiple known target collection, breast cancer genes collection, and network analysis has been used in this study. Results Four networks are set up—namely, ER-positive breast cancer network, compound-compound target network of DXP, DXP-ER-positive breast cancer network, and compound-known target-ER-positive breast cancer network. Some ER-positive breast cancer and DXP related targets, clusters, biological processes, and pathways, and several potential anticancer compounds are found. Conclusion This network analysis successfully predicted, illuminated, and confirmed the molecular synergy of DXP for ER-positive breast cancer, got potential anticancer active compounds, and found the potential ER-positive breast cancer associated targets, cluster, biological processes, and pathways. This work also provides clues to the researcher who explores ethnopharmacological or/and herbal medicine's or even multidrugs' various synergies.