Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Real-World Data of Pyrotinib-Based Therapy in Metastatic HER2-Positive Breast Cancer: Promising Efficacy in Lapatinib-Treated Patients and in Brain Metastasis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis. @*Materials and Methods@#One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included. @*Results@#Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea. @*Conclusion@#Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.

Current Status and Analysis of Cancer Chemotherapy Quality in Secondary and Tertiary Hospitals of Shanghai City / 中国医院管理

Objective To fully assess the status of cancer chemotherapy quality of secondary and tertiary hospitals in Shanghai City in order to improve the quality control system of cancer chemotherapy.Method According to the supervision plan of Shanghai Cancer Chemotherapy Quality Control Center,all of the 103 secondary and tertiary hospitals in Shanghai City which administrated chemotherapy to cancer patients have been inspected in 2015.SPSS13.0 was used for data aggregation and analysis.Result The cancer chemotherapy quality was significantly different between the secondary and tertiary hospitals,as well as between the oncoiogy and non-oncology departments,the main problems were as follow.:the informed consent content was incomplete (33.04％);pathological diagnosis was incomplete or missing (15.50％);tumor stage was not standardized or no staging (56.27％);the chemotherapy purposes (42.44％) and the chemotherapy indications (37.47％) and contraindications (12.21％) were incomplete or missing;the evaluation of chemotherapy efficacy was incomplete or not evaluated (24.10％);the mid-term assessment was incomplete or not evaluated (27.72％);admission history (16.28％) and records of the chemotherapy day (32.04％) were incomplete or missing.Conclusion The quality of medical records of cancer chem0therapy in Shanghai City is significantly related to hospital level and specialty.The hospital authorities should learn the quality control standards based on their own problems.

Effect of Remnant Preservation on Knee Joint Function and Proprioception Recovery in Anterior Cruciate Ligament Reconstruction under Arthroscope / 现代生物医学进展

Objective:To investigate the effects of ligamen remnant preservation on knee joint function and proprioception recovery in patients with anterior cruciate ligament (ACL) injuries during ACL reconstruction under arthroscope.Methods:The clinical data of 266 patients with ACL injuries,who were treated in the 174th hospital of PLA from January 2010 to March 2016,were retrospectively analyzed.All the patients underwent ACL reconstruction under arthroscopy,among them,163 patients with remnant preservation were chosen as remnant preservation group;103 patients with completely clearing remnant preservation in the operation,as non remnant preservation group.All the patients were followed up for more than 12 months,and the knee function and proprioception recovery of the two groups were evaluated.Results:There were no significant differences in the knee ipsilateral Lysholm score,international knee documentation committee knee assessment scale (IKDC) score,passive activity detection threshold,passive angle regeneration test results between the two groups before operation,9 and 12 months after operation (P＞0.05).The Lysholm scores and IKDC scores of the two groups at each time point were significantly higher than those before operation,the passive activity detection threshold and passive angle regeneration test results were significantly lower than those before operation (P＜0.05).The Lysholm scores and IKDC scores in the remnant preservation group 3 and 6 months after operation were higher than those in the non remnant preservation group,the passive activity detection threshold and the passive angle regenerated test results were lower than the non remnant preservation group,the difference was statistically significant (P＜0.05).Conclusion:Remnant preservation in the ACL reconstruction under arthroscopy can accelerate the recovery of knee joint function and proprioception,and satisfactory clinical results are achieved,which is worth popularizing.

A retrospective study of 500 mg fulvestrant in recurrent or metastatic breast cancer patients pretreat-ed with the third generation of aromatase inhibitors / 中国癌症杂志

Background and purpose:The third generation of aromatase inhibitors (AI) in postmenopausal hormone receptor-positive patients is the routine treatments in endocrine therapy. The 500 mg fulvestrant showed clini-cal beneifts in patients with previous AI treatment. This study aimed to access the effcacy and safety of 500 mg fulves-trant in estrogen receptor (ER) positive postmenopausal patients who had previous AI treatments with locally advanced and metastatic breast cancer.Methods:This study retrospectively analyzed the clinical data from 188 post-AI ER positive and (or) progesterone receptor (PR)-positive locally advanced and metastatic breast cancer patients treated with 500 mg fulvestrant in Fudan University Shanghai Cancer Center from Jul. 2011 to Dec. 2015. Primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR), clinical beneift rate (CBR) and safety proifle.Results:After the median follow-up of 11.3 months, median PFS was 5.9 months (95%CI: 4.2-7.5), CBR was 40.0% and ORR was 3.4%. COX proportional hazards regression analysis indicated that PFS was correlated with the number of metastatic sites (HR=1.92, 95% CI: 1.2-2.9,P =0.002) and previous lines of chemotherapy (HR=1.52, 95%CI:1.0-2.1,P=0.022). Six patients stopped the treatment for intolerable adverse events.Conclusion:The treatment of 500 mg fulvestrant has a favorable effcacy and safety in treatment of post-AI ER positive postmenopausal patientswith metastatic breast cancer.

The underlying mechanism of microRNA-21 in gemcitabine resistant breast cancer cells / 中国癌症杂志

Background and purpose:Gemcitabine-based chemotherapy has been shown to have signiifcant activity and favourable safety in metastatic breast cancer patients, but the effectiveness is limited due to drug resistance. MicroRNAs are a family of small non-coding RNA molecules, acting as oncogenes or tumor suppressors. Although various mechanisms of chemoresistance have been uncovered, the aberrant microRNA expression and its relationship with drug resistance of breast cancer are still unclear. This study explored the potential role and underlying mechanism of microRNA-21 in gemcitabine resistant breast cancer. Methods:MDA-MB-231 cells were continuously exposed to the increasing concentrations of gemcitabine to induce drug resistance to gemcitabine, which was 10 times more resis-tant. Then multiple methods were used including real-time PCR (RT-PCR), CCK-8, Western blot, transfection, wound healing and Transwell assay to observe the effect of microRNA-21 on epithelial-mesenchymal transition (EMT) and chemosensitivity. Results:The expression of microRNA-21 was up-regulated in gemcitabine resistant breast cancer cell line and inversely correlated with gemcitabine sensitivity. Manipulation of microRNA-21 status could change microR-NA-21 level, and could result in corresponding changes in EMT status and drug sensitivity. Conclusion:MicroRNA-21 induces gemcitabine resistance possibly via EMT process in breast cancer.

Progress on chemotherapy for triple negative breast cancer / 中国癌症杂志

Triple negative breast cancer (TNBC), as a special molecular subtype of breast cancer, is non-responsive to endocrine therapy or commercially available targeted therapy. It is characterized by early recurrence, rapid progression and poor prognosis. This systemic and comprehensive overview was focused on recent progress on molecular subtyping of triple negative breast cancer and its possible clinical value, chemotherapeutic agents and chemotherapy regimens, and combination of chemotherapy with potential molecular targeting agents.

Progress on the relationship between genetic polymorphism of CYP2D6 and endocrine therapy of breast cancer / 中国癌症杂志

CYP2D6 is one of the cytochrome P450 isozymes which are involved in the metabolism of various drugs with wide use. Polymorphism at the CYP2D6 locus is one of the most widely known causes for pharmacogenetic variability in humans beings. This review focuses on the importance of CYP2D6 polymorphism in the metabolism of tamoxifen, relationships between the genetic polymorphism and prognosis of patients who have underwent endocrine therapy, and evidences indicating that CYP2D6 may be used as a predictive marker for choosing optimal endocrine therapy for patients with breast cancer.

Methylation of gene promoter and chemorisistance / 中国癌症杂志

Mutation, translocation and loss of some genes have been known to contribute to chemoresistance, epigenetic mechanisms may also play an important role. About 29 000 CpG islands are primarily distributed in the promoter and the first exon regions of protein coding genes in normal cells. However, cancer cells exhibit significant changes in terms of DNA methylation, which can be summarized as global hypomethylation of the genome accompanied by focal hypermethylation. The relationship between aberrant methylation of gene in the promoter and chemoresistance was discussed in the review. A brief summary was also introduced with regard to the advances how in reversing aberrant methylation and overcoming chemoresistance.

Imatinib mesylate in the treatment of unresectable and/or metastatic gastrointestinal stromal tumors / 中国癌症杂志

Purpose:To evaluate the efficacy and toxicity of imatinib mesylate (STI571) in the treatment of unresectable and/or metastatic gastrointestinal stromal tumors (GIST).Methods:Ten patients with unresectable and/or metastatic GIST received imatinib at doses of 400 mg qd.Results:Among 9 evaluable patients, 4 achieved a partial response and 4 had stable disease. Ten patients were evaluable for toxicities. The nonhaematological toxicities included edema (mainly periorbital edema), abdominal pain, diarrhoea, nausea/vomiting, fatigue, intratumoural bleeding, intermittent muscle cramps and conjunctivitis. Myelosuppression was an infrequent side effect.Conclusions:Imatinib mesylate is an inhibitor of tyrosine kinase and has been proven to be active in patients with unresectable or metastatic GIST. Toxicity is acceptable.

Multivariate analyses of prognostic factors for breast cancer patients with liver involvement / 中国癌症杂志

Purpose:To investigate the prognostic factors for breast cancer patients with liver involvement.Methods:114 breast cancer patients with liver metastases,who were hospitalized in Fudan University Cancer Hospital between January,1996 and December,2003,were included in this study.Their survival data were analyzed.Results:The response rates with first-,second-,third-,fourth-line chemotherapy were 31.9%,27.8%,16.7% and 0%,respectively.Univariate analyses indicated that patients with impaired liver function and patients with a short interval between surgery and the first recurrence or metastasis had a poor prognosis.Multivariate analyses suggested that the presence of liver function impairment was an independent prognostic factor for overall survival.Conclusions:The response rates of chemotherapy drop with number of lines of chemotherapy.Breast cancer patients with liver involvement and impaired liver function have a poor prognosis.

Progress of the relationship between cyclooxygenase-2 and breast cancer / 中国癌症杂志

Recent researches indicated that cyclooxygena se -2 (COX-2) expression was related not only to development of breast cancer but also to clinicopathological parameters and prognosis of advanced breast cancer. The preclinical and clinical studies on the use of selective COX-2 inhibitors f or the prevention and treatment of breast cancer have become the focus of invest igation.