Pyrotinib Combined with Vinorelbine in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Single-Arm, Prospective Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. @*Materials and Methods@#This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. @*Results@#A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). @*Conclusion@#Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Maackiain inhibits proliferation and promotes apoptosis of nasopharyngeal carcinoma cells by inhibiting the MAPK/Ras signaling pathway / 中国天然药物

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.

Switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients progressing on abiraterone plus prednisone / 中华泌尿外科杂志

Objective:To evaluate the efficacy and safety of switch from prednisone (AA+ P) to dexamethasone (AA+ D) in metastatic castration-resistant prostate cancer patients (mCRPC) progressing on abiraterone plus prednisone.Methods:Between November 2016 and December 2019, 46 mCRPC patients were switched to AA+ D after progression on AA+ P at Sun Yet-sen University Cancer center. Median age was 72 years(50 to 89 years), with median androgen deprivation therapy (ADT) duration 14.6 months(2.1 to 168.5 months). PSA level at the time of diagnosis, the initiation of AA+ P treatment, the time of switch were 258.9 ng/ml, 56.6 ng/ml, 25.1 ng/ml, respectively. 42 (91.3%), 12(26.1%), 7(15.2%) patients had bone metastasis, lymph node metastasis, visceral metastasis, respectively. 28 patients had Gleason score ≥8, and 11 patients had Gleason score<8. The primary endpoint was progression free-survival (PFS). Secondary endpoints included PSA response rate of PSA decline ≥50% and ≥30% and safety. Patients were divided into different risk level groups according to PSA level at the time of switch and PFS on AA+ P.Results:The median follow-up of 46 patients was 4.9 months, 40 patients progressed at the last follow-up, the treatment was terminated in 1 patient because of cerebral infarction, 5 patients were still on the treatment of AA+ D. Median PFS on AA+ D of 46 patients was 3.7 (1.6-24.1) months. A total of 12 (26.1%) patients showed a PSA decline≥50% after treatment with AA+ D, and 21 (45.7%) patients showed a PSA decline ≥30%. The median PFS was 8.5 (2.7-24.1) and 3.0 (1.6-17.8) months for patients with PSA decline≥50% and PSA didn’t decline ≥50%, respectively. Four factors below were significantly associated with a longer PFS on AA+ D after steroid switch in univariate analysis: lower PSA level at the time of switch (<30 ng/ml, HR=0.30, 95% CI 0.14-0.64, P=0.002), longer ADT sensitivity duration (≥18 months, HR=0.55, 95% CI 0.28-1.06, P=0.045), longer AA+ P treatment PFS (≥8 months, HR=0.36, 95% CI 0.18-0.72, P=0.004), and greater PSA decline on AA+ D (≥50%, HR=0.30, 95% CI 0.17-0.75, P=0.007). The above mentioned factors were also independent prognostic factors associated with better PFS on AA+ D after steroid switch in multivariate analysis. Treatment with AA+ D was well tolerated in all patients, with no grade 3/4 toxicity reported. Conclusions:Switching from prednisone to dexamethasone is effective and safe in mCRPC patients progressing on abiraterone plus prednisone. Patients with lower PSA level at the time of switch, longer ADT sensitivity duration, longer AA+ P treatment PFS and greater PSA decline on AA+ D might gain better efficacy.

Efficacy and safety comparison of everolimus and fulvestrant in patients with estrogen receptor-positive advanced breast cancer progressed after endocrine therapy / 实用医学杂志

Objective To compare the efficacy and safety of everolimus combined with endocrine therapy and fulvestrant in patients with estrogen receptor-positive advanced breast cancer progressed after endocrine thera-py. Methods Ninety-three breast cancer patients were selected from January 2014 to February 2017. The primary end points were progression-free survival and clinical benefit rate and the secondary end points was tolerability. Re-sults The progression-free survival in fulvestrant group was slightly higher than that in the everolimus group(13.4 months vs 12.2 months,P = 0.297). The clinical benefit rates were 46.15% and 31.71% in fulvestrant group and everolimus group,respectively. Patients treated with fewer than 2 lines and endocrine resistant patients benefited more from fulvestrant but without statistical difference. The main adverse events related to everolimus were stomati-tis,with a prevalence rate of about 26% and a localized pneumonia with a prevalence rate of about 10%. The main adverse reaction of fulvestrant was the injection site reaction. Conclusions The efficacy of everolimus in combina-tion with endocrine therapy is not superior to that of fulvestrant for the treatment of advanced breast cancer pro-gressed after endocrine therapy. After weighing the clinical benefits and quality of life,fulvestrant may be better for patients treated with fewer than 2 lines and endocrine resistance.

Variation of CYP2D6 genotype between Caucasian and Asian population and inconsistency of serum endox-ifen concentration and phenotype of CYP2D6 in Chinese breast cancer patients / 实用医学杂志

Objective To conduct a prospective phase Ⅱ clinical study to explore the distribution of CYP2D6 gene polymorphism in Chinese population and its relationship with the metabolism of tamoxifen in early-stage hormonal receptor-positive breast cancer. Methods CYP2D6 genotype was tested by Sanger sequencing using the ABI 3500 Genetic Analyzer. Plasma concentrations of tamoxifen and endoxifen were measured using the HPLC-MS/MS(API 2000)assay. We downloaded the data of CYP2D6 allele from the CPIP database. Results In Chi-nese patients,the most common alleles were CYP2D6*1,*2,and *10;the predominant diplotypes were *1/*10 (38.3%)and*10/*10(18.8%). The distribution of metabolic phenotype,plasma concentration of endoxifen,and endoxifen:tamoxifen plasma concentration ratio were inconsistent between the normal metabolic phenotype(EM) and the intermediate phenotype(IM)under different CYP2D6 activity prediction criteria.The differences in the ratios and endoxifen plasma concentrations were statistically significant between the three groups by cluster analysis. Conclusions The CYP2D6 genotype distribution in Chinese population is different from that in the Western popu-lation. There is considerable variation of serum endoxifen concentration in Chinese breast cancer patients possess-ing the phenotype previously known as the intermediate active metabolizers of CYP2D6. Therefore,in the current era of precision medicine,the standard CYP2D6 genotype-phenotype classification system cannot properly stratify the Chinese population with different levels of endoxifen plasma concentration.

Construction of evaluation index system of nursing quality for cancer hospital / 中国实用护理杂志

Objective To establish a scientific and sensitive evaluation index system of nursing quality for cancer hospital. Methods The evaluation index system of nursing quality for cancer hospital was formulated based on literature,semi- structured interviews and expert group discussion. Then, developing the evaluation index system of nursing quality for cancer hospital by two rounds of Delphi consultation. Results The experts′ authority coefficient was 0.862. The nursing quality indicators included 5 first-level indicators,9 second-level indicators and 73 third-level indicators. The Kendall coordination coefficients of the importance of the three level indicators were 0.354,0.217,and 0.243, The Kendall coordination coefficients of the feasibility of the three level indicators were 0.234,0.313,and 0.339. Conclusions Scientific nature and concentration indicator system of nursing quality for cancer hospital was developed. It will be used to provide quantitative basis for the control of nursing quality in cancer hospital.

Analysis of clinicopathological characteristics and prognosis for triple negative breast cancer / 中国癌症杂志

Background and purpose: Triple negative breast cancer (TNBC) is a high risk breast cancer characterized by the negative expression of estrogen receptor(ER), progesterone receptor (PR) and Her-2 that have no specific therapy. This study was to analyze clinical pathological characteristics, survival, and prognostic factors of patients with TNBC. Methods: Clinical and pathological as well as follow-up data of TNBC, treated at the Cancer Centre of Sun Yat-sen University from Jan. 2000 to Dec. 2003, were collected and analyzed. Results: A total number of 128 women were identified as having triple negative breast cancer. The median age of these patients was 46 years, and 60.9% of them had stage Ⅰ or Ⅱ disease. The majority of pathological types were invasive ductal carcinomas, and 78.1% of tumors were staged T1 or T2. And 48.4% of these patients were involved in lymph node. Event-free survival, local replase-free survival, distant metastasis-free survival and overall survival at five years were 71.1%, 84.3%, 75.8% and 83.6% respectively. Though lymph node metastasis, tumor masses, stage and lymph-vascular invasion were all found to be related to overall survival, however, only lymph node metastasis and tumor masses affected the overall survival as revealed by the Cox proportional hazard model analysis. Conclusion: Triple negative breast cancer has distinct clinical and pathological characteristics. The patients are usually young, with large masses, lymph node metastasis, family history of breast cancer and poor prognosis; lymph node metastasis and tumor mass are important prognostic factors.

Efficacy and safety evaluation for 28 Chinese non-Hodgkin lymphoma patients treated with Hyper-CVAD/MA regimen / 肿瘤研究与临床

Objective To evaluate the efficacy and safety of the hyper-CVAD/MA regimen as an intensified treatment option for 28 T cell and aggressive/highly aggressive B cell NHL in Chinese patients. Methods Clinical data of 28 NHL patients treated with hyper-CVAD/MA regimen from Jan 2005 to Sep 2008 were retrospectively analyzed. Results 27 NHL patients were available for the efficacy analysis, with a response rate of 70.4 %. For the 13 B cell lymphoma cases, the response rate was 84.6 %. The main toxicity was Grade Ⅲ or Grade Ⅳ myelosuppression in all cases and 2 treatment related deaths. Conclusion Hyper-CVAD/MA regimen had a high response rate in T cell and aggressive /highly aggressive B cell NHL lymphoma, companied by significant toxicity when treating Chinese patients. Further clinical practices are needed to pick up a suitable dose which can balance efficacy and safety.

Clinical Significance of Approximated Molecular Subtypes of Invasive Breast Cancer / 中山大学学报(医学科学版)

[Objective] To investigate the clinical significance of approximated molecular subtype.[Methods] Four different subtypes were defined by immunohistochemical (IHC) markers as estrogen receptor (ER),progesterone receptor (PR) and HER2.Clinical characteristics as distribution,age,menopausal status,histopathologic type and grading,tumor size,lymph node status,time to and place of first tumor recurrence were analyzed.[Results] Among all 703 cases,Luminal A was the majority (51.5%) and the least were Luminal B and HER2+.90.8% the patients were less than 59 years old with Luminal A.Different subtype has different histopathologic grading.Luminal A was more than others among grading 1 tumors and it has more T1 tumors,while T4 tumors was most among HER2+ ones.Lymph nodes metastasis has no significant difference between different groups,other than high proportion tendency of N3 stage in Luminal B and HER2+.In addition,Luminal A has the longest time to the first recurrence while HER2+ was the shortest.Moreover,HER2+ and Basal-like have high rates of lung metastasis.Different from foreign reports,the distribution of the first recurrent place and distant metastases have no significant difference.[Conclusion] The classification of breast cancer approximated molecular subtype defined by IHC markers was feasible.The distribution is similar to other countries.Luminal A has rather better clinical characteristics while HER2+ and Basal-like have high rates of lung metastasis.However,Luminal A has the highest proportion of young patients,which is different from other countries.

DC loaded with CPP-Id increase the efficiency of CTL proliferation and enhance its cytotoxicity in vitro / 中国癌症杂志

Background and purpose:Dendritic cells(DCs) possess specialized feature such as pathogen recognition,antigen capturing and processing machinery,and stimulating naive T lymphocyte to have antitumor ability that allow them to act like professional APCs.This paper is aimed to confirm the impacts on the proliferation and secretion of INF-? of tumor specific CTL and its cytotoxocity induced by DC loaded with different antigen.Methods:After the stimulation of DC loaded with different antigen,the proliferative rate of allolymphocytes was measured by MTT and the cytotoxocity of CTL was evaluated with LDH method.The INF-? secreted by activated T lymphocytes was detected by ELISPOT.Results:The DC loaded with CPP-Id(320%?15%) had significantly induce T lymphocyte proliferating when comparing with the induction by DC loaded with Id(57%?10%)(P