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hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

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Chinese Journal of Cancer 2016年第6期35卷 46-52页

作者： Xue-Lian Chen Feng Du Ruo-Xi Hong Jia-Yu Wang Yang Luo Qing Li Ying Fan Bing-He Xu Department of Medical Oncology Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegePanjiayuanChaoyang DistrictBeijing 100021PRChina

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing ***,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast ***:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,*** median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or *** these 138 patients,79 received MCT,and 59 received ***?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 *** the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or *** then compared the MCT group and HT group in terms of treatment ***:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group *** in the MCT group,but the difference was not significant(43 vs.37

关键词： hormonal therapy Maintenance capecitabine monotherapy First-line capecitabine-based combination chemotherapy Metastatic breast cancer

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Effectiveness and adverse effects of hormonal therapy for prostate cancer： Japanese experience and perspective

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Asian Journal of Andrology 2012年第3期14卷 451-457,I0007,I0008页

作者： Mikio Namiki Satoru Ueno Yasuhide Kitagawa Takashi Fukagai Hideyuki Akaza Department of Integrative Cancer therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa 920-8640 Japan Department of Urology Showa University School of Medicine Tokyo 142-8666 Japan Research Center for Advanced Science and Technology University of Tokyo Tokyo 153-8903 Japan

Recently, novel anti-androgens and inhibitors of androgen biosynthesis have been developed through the elucidation of mechanisms of castration resistance of prostate cancer. We believe that these new developments will improve hormonal therapy. On the other hand, there has been an increase in criticism of hormonal therapy, because hormonal therapy is supposed to induce adverse effects such as cardiovascular disease. In this review, we have introduced the Japanese experience of hormonal therapy, because we believe that there may be ethnic differences between Caucasians and Asian people in the efficacy and adverse effects of hormonal therapy. First, we showed that primary hormonal therapy can achieve long-term control of localized prostate cancer in some cases and that quality of life of patients receiving hormonal therapy is rather better than previously thought. Neoadjuvant and adjuvant hormonal therapy in cases undergoing radical prostatectomy or radiotherapy are very useful for high-risk or locally advanced prostate cancer. Further clinical trials are required to confirm the efficacy of neoadjuvant or adjuvant hormonal therapy. We showed that the death from cardiovascular dis- eases in Japanese patients receiving hormonal therapy was not higher than that in the general population. However; efforts should be made to decrease the adverse effects of hormonal therapy, because life-style change may increase the susceptibility to adverse effects by hormonal therapy even in Japan. Managements of endocrine and metabolic dysfunction, such as diabetes mellitus, are essential. New hormonal compounds such as selective androgen receptor modulators capable of specifically targeting prostate cancer are expected to be developed.

关键词： adverse effects androgen deprivation therapy hormonal therapy prostate cancer

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The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

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Asian Journal of Andrology 2011年第3期13卷 499-504,515页

作者： Rui-Yi Wu Guo-Min Wang Lei Xu Bo-Heng Zhang Ye-Qing Xu Zhao-Chong Zeng Bing Chen Department of Urology Zhongshan Hospital Fudan University Shanghai 200032 China Evidence-Based Medicine Center Fudan University Shanghai 200032 China Department of Radiotherapy Zhongshan Hospital Fudan University Shanghai 200032 China

The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound （HIFU） combined with （＋） low-dose external beam radiotherapy （LRT） as supplemental therapy for advanced prostate cancer （PCa） following hormonal therapy （HT）. Our definition of HIFU＋LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy （CRT）. We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU＋LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU ＋LRT treatment. There were significant differences among four groups with regard to overall survival （OS） and disease-specific survival （DSS） curves （P=0.018 and 0.015）. Further comparison between each pair of groups suggested that the long-term DSS of the H IFU ＋ LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU＋LRT group and the CRT group. Multivariable Cox＇s proportional hazard model showed that both HIFU＋LRT and CRT were independently associated with DSS （P=0.001 and 0.035） and had protective effects with regard to the risk of death. Compared with CRT, HIFU ＋LRT significantly decreased incidences of radiation-related late gastrointestinal （GI） and genitourinary （GU） toxicity grade ≥ II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and reRional lymph node metastases after HT. As an alternative to CRT, HIFU＋LRT showed Rood efficacy and better safety.

关键词： complication high-intensity focused ultrasound hormonal therapy low-dose external beam radiotherapy prostate cancer survival rate

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Impact of cytochrome P450 2D6 polymorphisms on decision-making and clinical outcomes in adjuvant hormonal therapy for breast cancer

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World Journal of Clinical Oncology 2022年第8期13卷 712-724页

作者： Ern-Yu Tan Lavina Bharwani Yee-Hong Chia Richie C T Soong Sherylyn S Y Lee Juliana J C Chen Patrick M Y Chan Department of General Surgery Tan Tock Seng HospitalSingapore 308433Singapore Lee Kong Chian School of Medicine Singapore 308232Singapore Institute of Molecular and Cell Biology A*STARSingapore 138673Singapore Department of Medical Oncology Tan Tock Seng HospitalSingapore 308433Singapore Cancer Science Institute of Singapore National University of SingaporeSingapore 119077Singapore

BACKGROUND There are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P4502D6(CYP2D6)*** To evaluate how knowledge of CYP2D6 genotype impacted the choice of hormonal agent and how CYP2D6 genotype and agent were associated with clinical *** Eighty-two women were ***-eight completed CYP2D6 genotyping and were categorized into poor,intermediate(IM)and extensive or ultra metabolizer *** with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred *** More than 70%of the women had an IM phenotype,32%an extensive or ultra metabolizer phenotype,and 0%had a poor metabolizer *** of genotype,more women opted for aromatase ***,80%of women completed 5 years of hormonal *** women developed recurrence,3 contralateral breast cancer,5 died,and 1 was diagnosed with a second primary ***-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype,though not statistically significant[P=0.743,hazard ratio(HR):1.441,95%confidence interval(CI):0.191 to 10.17 and P=0.798,HR:1.327,95%CI:0.172 to 9.915,respectively].Women receiving aromatase inhibitors also appeared to have a better,but also nonsignificant,5-year recurrence-free and overall survival(P=0.253,HR:0.368,95%CI:0.031 to 0.258 and P=0.292,HR:0.252,95%CI:0.005 to 4.951,respectively).CONCLUSION The IM phenotype was highly prevalent but was not associated with clinical outcome.

关键词： Functional cytochrome P4502D6 polymorphisms Breast cancer hormonal therapy

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Treatment strategy for metastatic prostate cancer with extremely high PSA level： reconsidering the value of vintage therapy

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Asian Journal of Andrology 2018年第5期20卷 432-437页

作者： Yasutaka Yamada Shinichi Sakamoto Yoshiyasu Amiya Makoto Sasaki Takayuki Shima Akira Komiya Noriyuki Suzuki Koichiro Akakura Tomohiko Ichikawae Hiroomi Nakatsu Department of Urology Asahi General Hospital Asahi 289-2511 Japan Department of Urology Chiba University Graduate School of Medicine Chiba 260-8677 Japan Department of Urology Japan Community Healthcare Organization Tokyo Shinjuku Medical Center Tokyo 162-8543 Japan

The prognostic significance of initial prostate-specific antigen （PSA） level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows： low （〈100 ng ml-1）, intermediate （100–999 ng ml-1）, and high （≥1000 ng ml-1）. All patients received androgen deprivation therapy （ADT） immediately. We investigated PSA progression-free survival （PFS） for first-line ADT and overall survival （OS） within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal （AW） and alternative antiandrogen （AA） therapies after development of castration-resistant prostate cancer （CRPC）. No significant differences in OS were observed among the three groups （P = 0.654）. Patients with high PSA levels had significantly short PFS for first-line ADT （P = 0.037）. Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group （P = 0.047）. Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy （P = 0.049）. PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders （P = 0.011 and P 〈 0.001, respectively）. Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

关键词： alternative antiandrogen therapy antiandrogen withdrawal hormonal therapy metastatic prostate cancer prostate-specificantigen

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Potential therapeutic effect of epigenetic therapy on Ireatment-induced neuroendocrine prostate cancer

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Asian Journal of Andrology 2017年第6期19卷 686-693页

作者： Xiang Xu Yu-Hua Huang Yan-Jing Li Alexa Cohen Zhen Li Jill Squires Wei Zhang Xu-Feng Chen Min Zhang Jiao-Ti Huang School of Life Sciences Anhui University Hefei China Department of Pathology and Laboratory Medicine University of California at Los Angeles Los Angeles California USA Department of Urology The First Affiliated Hospital of SooChow University Suzhou China Department of Medical Oncology Rutgers Cancer Institute of New Jersey New Brunswick New Jersey USA Department of Pathology Beijing Hospital Beijing China

Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model （LNCaP/NE1.8） to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.

关键词： cancer stem cell epigenetic therapy hormonal therapy neuroendocrine prostate cancer suberoylanilide hydroxamic acid

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Hormone naive prostate cancer： predicting and maximizing response intervals

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Asian Journal of Andrology 2015年第6期17卷 929-935,I0007,I0008页

作者： Judd W Moul Division of Urology Department of Urology Duke Cancer Institute Duke South Duke University Medical Center Durham NC 27710 USA.

Hormone naive advanced prostate cancer is subdivided into two disease states： biochemical recurrence and traditional M 1 （metastatic） prostate cancer and characterized by no prior hormonal therapy or androgen deprivation therapy （ADT）. In biochemical recurrence/ prostate-specific antigen （PSA） recurrence, men should be risk-stratified based on their PSA doubling time, the Gleason score and the timing of the recurrence. In general, only men who are at high risk should be considered for early/immediate ADT although this is best done using shared decision with the patient. The type of ADT to be used in biochemical recurrence ranging from oral-only peripheral blockade （peripheral androgen deprivation） to complete hormonal therapy （combined androgen blockade [CAB]） remains in debate owing to lack of randomized controlled trials （RCT）. However, there is good RCT support for use of intermittent hormonal therapy （IHT）. There is also limited research on biomarker response （PSA and testosterone decline） to predict prognosis. On the other hand, in the setting of M1 hormone naive prostate cancer, there are many more RCT＇s to inform our decisions. CAB and gonadotrophin-releasing hormone antagonists perhaps provide a slight efficacy advantage while IHT may be slightly inferior with minimal M1 disease. The PSA nadir at 7 months after starting ADT is a powerful prognostic tool for M1 patients. There is growing recognition that serum testosterone （T） control while on ADT is linked to the development of castrate-resistant prostate cancer. Especially for a M 1 patient, maintaining a serum T below 20-30 ng d1-1 prolongs the response to ADT. Novel oral agents （abiraterone and enzalutamide） may soon find use in hormone naive disease and may alter the treatment landscape. Despite over 75 years of experience with ADT, many questions remain, and the field continues to evolve.

关键词： androgen deprivation therapy cancer gonadotrophin-releasing hormone antagonists hormonal therapy luteinizing hormone-releasing hormone agonists prostate prostate-specific antigen testosterone

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The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

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Asian Journal of Andrology 2009年第3期11卷 299-307页

作者： Kaori Yamamoto-Ishikawa Hiroyoshi Suzuki Masahiko Nezu Naoto Kamiya Takashi Imamoto Akira Komiya Kazuyuki Sogawa Takeshi Tomonaga Fumlo Nomur Tomohiko Ichikawa Department of Urology Graduate School of Medicine Chiba University Chiba 260-8670 Japan Department of Molecular Diagnosis Graduate School of Medicine Chiba University Chiba 260-8670 Japan

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients＇ sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points： point A, pre-treatment; point B, at the nadir of the prostate- specific antigen （PSA） level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients＇ sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I （ApoC-I）. Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-i protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.

关键词： apolipoprotein C-I hormonal therapy prognosis prostate cancer surface-enhanced laser desorption/ionization time-offlight mass spectrometry

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Advances in non-surgical management of primary liver cancer

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World Journal of Gastroenterology 2014年第44期20卷 16630-16638页

作者： Xiao Chen Hai-Peng Liu Mei Li Liang Qiao Department of General Surgery Lanzhou University Second Hospital Key Laboratory of Digestive System Tumors of Gansu Province Storr Liver Unit Westmead Millennium Institute Department of Medicine and Western Clinical School University of Sydney

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.

关键词： Ablation therapy Biotherapy Hepatocellular carcinoma hormonal therapy Percutaneous ethanol injection Percutaneous microwave coagulation therapy Radiofrequency ablation Radiotherapy Transcatheter arterial chemoembolization Chemotherapy

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Cronkhite-Canada syndrome with esophagus involvement and sixyear follow-up:A case report

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World Journal of Gastroenterology 2024年第8期30卷 984-990页

作者： Yu-Chen Tang Department of Endocrinology The First Affiliated Hospital of Ningbo UniversityNingbo 315000Zhejiang ProvinceChina

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare,noninherited disease characterized by gastrointestinal polyposis with diarrhea and ectodermal *** polyps are distributed through the whole digestive tract,and they are common in the stomach and colon but very uncommon in the *** SUMMARY Here,we present a case of a 63-year-old man with skin hyperpigmentation accompanied by diarrhea,alopecia,and loss of his *** data indicated anemia,hypoalbuminemia,hypocalcemia,hypokalemia,and positive fecal occult *** showed numerous polyps scattered throughout the digestive tract,including the *** was treated with nutritional support and glucocorticoids with remission of his *** Comprehensive treatment led by hormonal therapy can result in partial or full remission of clinical *** should be individualized for each patient according to their therapy *** endoscopy is necessary for assessing mucosal disease activity and detecting malignant transformation.

关键词： Cronkhite-Canada syndrome Gastrointestinal polyposis hormonal therapy Prognosis Case report

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