A bleeding heart: case report and review of pericardial angiosarcoma

Abstract Primary cardiac tumors are rare. The cardiac sarcomas are the most common malignant cardiac tumors. These tumors have a dismal prognosis with an overall median survival of 25 months. Clinical features include dyspnea, arrhythmias, pericardial effusions, heart failure, and sudden cardiac death. The diagnosis is often challenging. Therefore, the cardiac imaging workup plays a central role in addition to a high clinical suspicion in the setting of atypical presentations that do not respond to standard therapies. The echocardiography, computed tomography, and cardiac MRI are crucial in clinching the diagnosis. Multimodal treatment with surgery, chemotherapy, and radiotherapy has been shown to improve outcomes, as opposed to using either of these modalities alone. We describe the case of a 30-year-old gentleman with COVID-19 infection who developed recurrent hemorrhagic pericardial effusions refractory to standard treatment and was eventually diagnosed as a case of pericardial angiosarcoma after his biopsy revealed the diagnosis and staging was performed using PET-CT-FDG scan. Our case re-emphasizes the importance of considering a malignant etiology early in the course of the disease presentation, especially in recurrent hemorrhagic effusions despite an inflammatory cytologic diagnosis of fluid. It also highlights the place for cardiac CT and MRI to ascertain the location and spread and to plan the further course of treatment. If diagnosed early, the estimated survival time can be prolonged by instituting a multimodal approach.

Meta-analysis of the effects of ABCB1 genotype on the efficacy and safety of taxanes in the treatment of breast cancer / 中国药房

OBJECTIVE To evaluate the effects of ABCB1 genotypes on the efficacy and safety of taxanes in the treatment of breast cancer. METHODS By searching Embase，the Cochrane Library， PubMed， CNKI， and Wanfang databases， cohort studies and case-control studies about taxanes in the treatment of breast cancer were collected from the establishment of the database to July 2023. After screeningliterature， extracting data and evaluating quality， meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 studies were included， involving 1 321 patients. There was no correlation between the three genotypes and effective rate， the incidence of myelosuppression， the incidence of neurotoxicity （except for the allele and recessive model of ABCB1 C1236T）， and the incidence of hypersensitivity reactions （P＞0.05）. The subgroup analysis showed that there was a correlation between ABCB1 C1236T dominant model and effective rate when using anthracyclines+5-fluorouracil+cyclophosphamide+taxanes （P＜0.05）， there was a correlation between ABCB1 C3435T recessive model and effective rate when using taxanes+trastuzumab （P＜0.05）. ABCB1 C1236T allele model and recessive model were correlated with sample size ≥100 and using cyclophosphamide+epirubicin+5- fluorouracil+paclitaxel or cyclophosphamide+epirubicin+paclitaxel+trastuzumab or cyclophosphamide+epirubicin+5-fluorouracil+ trastuzumab+paclitaxel regimens； recessive model with sample size ＜100 and the African region were correlated with the incidence of peripheral neuropathy； recessive model was correlated with cutaneous adverse reactions （P＜0.05）. ABCB1 C3435T recessive model was correlated with the incidence of reduced neutrophil count with sample size ≥100； the incidence of white blood cell count reduction with sample size ＜100 and using docetaxel+epirubicin+cyclophosphamide was correlated with both the allele model and the dominant model； the incidence of infections was correlated with the dominant model （P＜0.05）. The incidence of neutrophil count reduction with the sample size ＜100 was correlated with allele model of ABCB1 G2677T/A； the incidence of edema with sample size ≥100 was correlated with allele model and recessive model； the incidence of infection was correlated with allele model and dominant model， especially in patients with neutrophil count complicated with fever （P＜0.05）. CONCLUSIONS ABCB1 genotypes are not correlated with effective rate of taxanes in the treatment of breast cancer， but ABCB1 C3435T genotype is associated with decreased neutrophil counts， decreased white blood cell counts and infections； ABCB1 C1236T genotype is associated with neurotoxicity and cutaneous adverse reactions； ABCB1 G2677T/A genotype is associated with decreased neutrophil counts， infections， and edema.

Progress in A Real-world Study of Abiraterone Acetate Versus Docetaxel in Patients with Metastatic Hormone-sensitive Prostate Cancer / 肿瘤防治研究

The safety and survival benefits of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer have been confirmed by randomized controlled trials and clinical studies abroad. However, real-world studies remain lacking. In this article, we review the progress of real-world studies of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer and the problems faced in clinical practice against the background of differentiated real-world studies. Further research is needed to address clinically important issues, such as individualized dosing, combination dosing, and monitoring of adverse effects.

Febrile neutropenia incidence and the variable toxicity profile between brand and generic docetaxel in the adjuvant treatment of breast cancer with docetaxel and cyclophosphamide regimen

ABSTRACT Objective To assess the incidence of febrile neutropenia without primary granulocyte colony-stimulating factor prophylaxis in patients undergoing chemotherapy with adjuvant docetaxel and cyclophosphamide, and to evaluate the toxicity profile of brand-name docetaxel (Taxotere ® ) and the generic formulation. Methods This retrospective study was conducted using data obtained from electronic medical records of patients treated at a Brazilian cancer center. Patients with breast cancer who underwent adjuvant treatment between January 2016 and June 2019 were selected. Data were analyzed using chi-square and Fisher correlation of variables, and multivariate analyses were adjusted for propensity score. Results A total of 231 patients with a mean age of 55.9 years at the time of treatment were included in the study. The majority (93.9%) had luminal histology, 84.8% were at clinical stage I, and 98.2% had a good performance status. The overall incidence of febrile neutropenia in the study population was 13.4% (31 cases). The use of brand-name docetaxel (Taxotere ® ) was the only factor associated with febrile neutropenia occurrence (OR= 3.55, 95%CI= 1.58-7.94, p=0.002). Conclusion In patients with breast cancer who require treatment with adjuvant docetaxel and cyclophosphamide regimen, the toxicity profile differs between brand-name and generic docetaxel. Regardless of the formulation used, the incidence of febrile neutropenia was less than 20%, which may allow for the omission of primary prophylactic granulocyte colony-stimulating factor use in this setting.

Self-assembly of CXCR4 antagonist peptide-docetaxel conjugates for breast tumor multi-organ metastasis inhibition

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Study on pharmacokinetics of novel lung-targeted Docetaxel liposome in in-situ lung cancer model rabbit / 中国药房

OBJECTIVE To study the pharmacokinetic behavior of novel lung-targeted Docetaxel liposome （DTX-LP） in in- situ lung cancer model rabbit. METHODS The content of DTX in rabbit plasma was determined by UPLC-MS/MS， and methodology investigation was conducted. in-situ lung cancer model rabbit was made by the ultra-minimal invasive percutaneous puncture inoculation method. Model rabbits were randomly divided into Docetaxel injection （DTX-IN） group and DTX-LP group. The rabbits were given relevant medicine via ear vein at a dose of 1.0 mg/kg （calculated by DTX）； blood was taken at 5， 15， 30， 60， 90， 120， 240 and 480 minutes to measure the concentration of DTX in plasma. DAS 3.3 software was adopted for fitting and analysis， and to calculate pharmacokinetic parameters. RESULTS UPLC-MS/MS method used in this study was accurate and precise， which met the requirements of biological sample analysis. Compared with DTX-IN group， drug concentration-time curve of DTX-LP was smoother， the blood concentration at each time point was lower， and cmax， t1/2， AUC0→480 min and AUC0→∞ were significantly decreased （P＜0.05）. CONCLUSIONS The drug exposure of DTX-LP in plasma is significantly reduced than DTX- IN， indicating it can be rapidly distributed from systemic circulation to liver target organs.

Effects of centralized volume-based procurement policy on the use of drugs for non-small cell lung cancer in a third-grade class-A cancer hospital / 中国药房

OBJECTIVE To analyze the effects of centralized volume-based procurement policy （hereinafter referred to as “centralized procurement”） on the use of anti-tumor drugs in medical institutions. METHODS The interrupted time series model was used to analyze the changes in the monthly purchase volume and purchase amount of docetaxel， gemcitabine and pemetrexed disodium in a third-grade class-A cancer hospital in Shanxi province from January 2018 to December 2021. RESULTS & CONCLUSIONS After the implementation of the centralized procurement policy， both the selected drugs and the non-selected drugs had different degrees of price reduction， and the price reduction of the selected drugs was far greater than that of the non- selected drugs； average monthly purchase volume and amount of docetaxel decreased significantly in that month after the implementation of the policy， while those of gemcitabine and pemetrexed disodium increased significantly （P＜0.05 or P＜0.01）. After the implementation of the policy， the average monthly purchase volume and amount of gemcitabine showed a downward trend， while those of docetaxel and pemetrexed disodium showed an upward trend （P＜0.05 or P＜0.01）. It is suggested that hospitals should strengthen pharmaceutical administration， and avoid adopting a “one size fits all” approach to non-selected drugs； relevant departments should further expand the collection range of anti-tumor drugs or carry out special collection of anti-tumor drugs， so as to save medical insurance funds and reduce medical expenses.

Efficacy and safety of Shenqi Fuzheng injection combined with docetaxel treatment regime in patients with metastatic castration-resistant prostate cancer / 中国药师

Objective To explore the efficacy and safety of Shenqi Fuzheng injection(SFI)combined with docetaxel treatment regime in patients with metastatic castration-resistant prostate cancer(mCRPC).Methods The present studyretrospectively selected mCRP patients diagnosed and treated in the department of urology of Weinan Central Hospital from January 2017 to January 2022 from the electronic medical record system.According to the treatment plan,mCRPC patients were divided into Docetaxel group and Docetaxel+SFI group,receiving docetaxel+prednisone acetate treatment and docetaxel+prednisone acetate+SFI treatment,respectively.The short-term efficacy[objective response rate(ORR)and disease control rate(DCR)]and long-term efficacy[progression free survival(PFS)and overall survival(OS)]of two groups of mCRPC patients were eveluated.The occurrence of adverse reactions during treatment in mCRPC patients was eveluated using were eveluated the common terminology standard for good events(CTCAE 4.03).Results A total of 305 mCRPC patients were included in this study,including 159 cases in Docetaxel+SFI group and 146 cases in Docetaxel group.The ORR and DCR of the Docetaxel+SFI group were significantly higher than those of the Docetaxel group(P＜0.05).The median PFS and median OS of mCRPC patients in the Docetaxel+SFI group were significantly higher than those in the camrelizumab group(P＜0.001).In addition,the incidence of adverse events such as hair loss,diarrhea,nausea and vomiting,anorexia,peripheral edema,and neutropenia in mCRPC patients in the Docetaxel+SFI group was significantly lower than that in the Docetaxel group(P＜0.05).Conclusion Shenqi Fuzheng injection combined with docetaxel has a significant therapeutic effect on mCRP patients,which can improve disease control rate,prolong PFS and OS,and reduce the incidence of adverse reactions.

Effects of TPF regimen and IMRT on immune function and survival prognosis of patients with advanced esophageal cancer / 国际肿瘤学杂志

Objective:To study the effects of docetaxel, cisplatin and fluorouracil (TPF) regimen simultaneous intensity modulated radiotherapy (IMRT) on immune function and survival prognosis of patients with advanced esophageal cancer.Methods:A total of 93 patients with advanced esophageal cancer were screened in Hebei Veterans General Hospital from June 2015 to December 2017, and were divided into two groups using randomized envelope method. The observation group (47 cases) was given synchronous TPF regimen and IMRT, and the control group (46 cases) was given synchronous PF regimen (cisplatin combined with fluorouracil) and IMRT. Esophageal barium meal, chest and upper abdominal CT were reviewed within 1 month after treatment to assess the short-term efficacy and compare the immune function of the two groups before and after treatment. Kaplan-Meier survival curve was plotted to evaluate the long-term efficacy based on overall survival (OS). The incidence of adverse reactions in the two groups was collected to evaluate their safety.Results:After treatment, the T cell subgroup CD8 + level of the observation group was higher than that of the control group [(33.55±4.46)% vs. (29.06±3.61)%, P<0.05], while CD3 + [(51.29±5.22)% vs. (56.04±6.10)%, P<0.05], CD4 + [(28.27±3.63)% vs. (30.35±3.52)%, P<0.05] and CD4 + /CD8 + (0.84±0.25 vs. 1.04±0.08, P<0.05) levels were lower than those of the control group. The effective rate of recent treatment in the observation group was 82.98% (39/47), while the effective rate in the control group was only 63.04% (29/46), with a statistically significant difference ( χ2=4.70, P=0.030). The median OS of the observation group was 25.3 months (95% CI: 17.9-26.1), and that of the control group was 18.2 months (95% CI: 14.4-25.5), with a statistically significant difference ( χ2=3.28, P=0.038). Adverse reactions during the follow-up period of the two groups of patients were mainly nausea/vomiting, fatigue, anorexia, hematological toxicity, esophagitis and pneumonia, etc., which were mostly grade 1-2, and disappeared after symptomatic treatment or termination of treatment. Compared with the control group, the incidence of nausea/vomiting (46.81% vs. 78.26%, χ2=9.80, P=0.002), anorexia (44.86% vs. 71.74%, χ2=6.99, P=0.008), leukopenia (36.96% vs. 73.91%, χ2=13.37, P<0.001) and esophagitis (61.70% vs. 82.61%, χ2=5.05, P=0.025) adverse reactions was lower in the observation group. Conclusion:TPF combined with IMRT has high efficacy and low adverse reactions, which can be used as an effective treatment to improve the survival prognosis of patients with advanced esophageal cancer.

GSDME promoter methylation regulates the chemotherapy sensitivity of breast cancer cells through pyrolysis / 中华内分泌外科杂志

Objective:To explore the mechanism by which GSDME promoter methylation regulates the chemotherapy sensitivity of breast cancer (BC) cells through pyrolysis.Methods:Tissues of 54 cases with BC treated with chemotherapy were collected and divided into chemotherapy resistant group and sensitive group. Docetaxel (DTX) was used to treat BC cells to establish drug-resistant BC cells. CCK8 was used to detect cell resistance.qRT-PCR was used to detect the expression of GSDME in tissues and cells. Then sulfite sequencing method was utilized to determine the methylation level of the GSDME promoter methylation site. The expression level of GSDME in DTX-treated BC cells was intervened, and qRT-PCR was used to detect the expression level of Caspase-1, Caspase-4, IL-1β, and IL-18 in cells to assess the degree of cell pyrolysis.Results:Compared with the chemotherapy sensitive group, the expression of GSDME was down-regulated in the chemotherapy resistant group ( t=6.54, P<0.001) . Compared with MCF-10A cells, Caspase-1 ( t=9.14, P<0.001) , Caspase-4 ( t=9.35, P<0.001) , IL-1β ( t=6.13, P=0.004) , and IL-18 ( t=5.49, P=0.005) expression level in MCF-10A/DTX cells were decreased, however, the above indicators were up-regulated after overexpression of GSDME in MCF-10A/DTX cells. Hypermethylation in GSDME promoter region led to a decrease in mRNA expression ( t=12.56, P<0.001) . In tolerance tissues, the methylation level in the GSDME promoter region was negatively correlated with the mRNA level ( r=-0.57, P=0.010) . After treating MCF-10A/DTX cells with 5-azacytidine, a methylation inhibitor,Caspase-1, Caspase-4, IL-1β, IL-18 levels were significantly increased, and GSDME level were up-regulated. Conclusion:Hypermethylation in the promoter region of GSDME leads to decreased mRNA expression, inhibits pyrolysis of BC cells, and reduces the sensitivity of DTX chemotherapy.

Effects of nedaplatin combined with docetaxel on serum tumor markers and T lymphocyte subsets in patients with ovarian epithelial carcinoma / 中国基层医药

Objective:To investigate the effects of nedaplatin combined with docetaxel on serum tumor markers and T lymphocyte subsets in patients with epithelial ovarian cancer.Methods:Ninety-two patients with epithelial ovarian cancer who received treatment from March 2016 to December 2017 were included in this study. They were randomly assigned to undergo nedaplatin combined with docetaxel (observation group, n = 46) or cisplatin combined with paclitaxel (control group, n = 46). Both groups received two 21-day courses of treatment. Serum tumor marker level, T lymphocyte subset level, clinical efficacy, incidence of adverse reactions, and 2-year survival rate were compared between the two groups. Results:After treatment, serum cancer antigen 125 (CA125), cancer antigen 199 (CA199), and carcinoembryonic antigen (CEA) levels were (45.84 ± 22.46) U/mL, (35.13 ± 15.03) U/mL, (16.21 ± 3.20) U/mL, respectively in the control group and they were (28.33 ± 20.11) U/mL, (14.82 ± 10.11) U/mL, (5.16 ± 1.33) U/mL, respectively in the observation group. After treatment, CA125, CA199, and CEA levels in each group were significantly decreased compared with before treatment. After treatment, CA125, CA199, and CEA levels were significantly lower in the observation group than in the control group ( t = 3.94, 7.61, 21.63, all P < 0.05). After treatment, the numbers of CD3 +, CD4 +, CD8 + cells in the control group were (16.22 ± 3.12)%, (15.20 ± 1.46)%, (29.21 ± 5.17)%, respectively, and they were (31.22 ± 4.11)%, (24.99 ± 1.71)%, (24.25 ± 4.45)% respectively in the observation group. After treatment, the numbers of CD3 + and CD4 + cells in the observation group were significantly higher than those in the control group ( t = 19.72, 29.53, both P < 0.05). After treatment, the number of CD8 + cells in the observation group was significantly lower than that in the control group ( t = 4.93, P < 0.05). Total response rate was significantly higher in the observation group than in the control group [78.26% (36/46) vs. 58.70% (27/46), χ2 = 4.08, P < 0.05]. The incidence of adverse reactions was significantly lower in the observation group than in the control group [23.91% (11/46) vs. 45.65% (21/46), χ2 = 4.79, P < 0.05]. The 2-year survival rate was significantly higher in the observation group than in the control group [43.48% (20/46) vs. 23.91% (11/46), χ2 = 3.94, P < 0.05]. Conclusion:Nedaplatin combined with docetaxel is highly effective on epithelial ovarian cancer. The combined therapy can greatly reduce serum CA125, CA199, and CEA levels but has no great effects on T lymphocyte subsets. It can increase the survival rate but has no serious adverse reactions.

Establishment and validation of population pharmacokinetic model of docetaxel in malignant tumor patients / 中国药房

OBJECTIVE To establis h and validate a population pharmacokinetic model of docetaxel in malignant tumor patients. METHODS The clinical data of malignant tumor patients treated with chemotherapy regimen containing docetaxel in our hospital from June 2019 to December 2021 were retrospectively collected . According to the results of blood concentration detection ， based on the three -compartment model the nonlinear mixed effect model （NONMEM）was used ；covariates（age，weight，height， body surface area ，Karnofsky performance scale ，total protein ，albumin，total bilirubin ，aspartate aminotransferase ，alanine aminotransferase and serum creatinine ）affecting clearance （CL）were screened by “forward inclusion and backward exclusion ”； the population pharmacokinetic model of docetaxel was established . The model was tested for goodness -of-fit diagnosis and internal validation by Bootstrap . RESULTS A total of 264 measured blood concentrations of 132 patients with malignant tumors during chemotherapy were included . The covariates that had significant effect on CL of docetaxel were serum creatinine and total bilirubin （P＜0.01）. The results of Bootstrap analysis （parameter median values and 95% confidence intervals ）were close to predict results of the established model ；the final model estimated that the population typical value of docetaxel CL was 37.82 L/h. CONCLUSIONS The population pharmacokinetic model of docetaxel in malignant tumor patients is established successfully ， which can be used for the formulation and optimization of clinical individualized regimen .

Effect of renal failure on docetaxel exposure and adverse reactions in breast cancer patients / 药学实践与服务

Objective To investigate the influence of renal failure on the area under curve (AUC) and adverse reactions of docetaxel in breast cancer patients, and provide evidence for the dosage of docetaxel in renal failure patients. Methods A retrospective study was conducted on 24 patients with breast cancer who had undergone radical mastectomy and received AC-T adjuvant chemotherapy in our hospital from January 2019 to November 2021. According to renal function cases, the patients were divided into two groups: renal failure group (n=5) and normal renal function group (n=19). The clinical characteristics such as gender, age, body weight and body surface area of patients in two groups, docetaxel dose, blood concentration, area under the curve, liver and kidney function, white blood cell count and absolute value of neutrophil before chemotherapy were collected. Single factor linear regression was used to analyze the influencing factors of the AUC of docetaxel. Adverse reactions after chemotherapy with docetaxel including nausea and vomiting, bone marrow suppression, constipation and liver function injury were collected. CTCAE 4.0 evaluation standard was used to evaluate adverse reactions. Results The clinical characteristics of creatinine [908.0 (819.0, 1018.0) μmol/L vs 54.8 (52.0, 65.0) μmol/L] and creatinine clearance rate [4.9 (4.3, 5.4) ml /min vs 86.3 (59.3, 92.5) ml/min] of the renal failure group and the normal renal function group have significant difference (P<0.001), while no significant difference (P>0.05) were found in the body surface area [1.4 (1.4, 1.5) m2 vs 1. 6 (1.5, 1.6) m2], docetaxel dose [70.4 (69.4, 73.0) mg/m2 vs 74.4 (72.3, 91.2) mg/m2], body weight [(51.4±3.8) kg vs (51.5±5.5) kg]. Liver function, white blood cells and neutrophils were within the normal range before chemotherapy with docetaxel. There was no significant difference in AUC value [(1.6±0.6) mg·h/L vs (1.8±0.8) mg·h/L] between the two groups after chemotherapy with docetaxel (P>0.05). Linear univariate regression analysis indicated that the blood concentration at the end of docetaxel infusion was significantly associated with AUC of docetaxel (P<0.001), while the body surface area, dose of docetaxel, body weight, liver and kidney function were not correlated with AUC of docetaxel (P>0.05). After chemotherapy with docetaxel, adverse reactions of patients in the two groups: nausea and vomiting (grade I incidence: 40% vs. 57.9%, grade II incidence: 60% vs. 42.1%), myelosuppression (grade I incidence: 60% vs. 84.2%, grade II incidence: 20% vs 15.8%) and constipation (all mild constipation) had no significant difference (P>0.05). Conclusion Renal failure did not affect the exposure of docetaxel and the adverse reactions after chemotherapy with docetaxel in breast cancer patients.

Efficacy and safety of docetaxel plus hormone therapy in metastatic prostate cancer / 中华泌尿外科杂志

Objective:To evaluate the efficacy and safety of docetaxel plus hormone therapy in metastatic prostate cancer.Methods:From April 2016 to April 2019, 204 cases with bone metastatic prostate cancer in the Second Hospital of Tianjin Medical University were analyzed retrospectively. There were 97 patients responded to hormone therapy including 92 cases with high-burden metastasis (more than 4 bone metastases with one or more beyond the axial skeleton) and 5 cases with low-burden metastasis, with average age of 70 years (range 42-87 years) and median prostate specific antigen (PSA) of 74.1 ng/ml (range 11.0-145.0 ng/ml). Among them, there were 35 patients (36.1%) with a Gleason score of 7 or lower, and 62 patients (63.9%) with a Gleason score of 8 or higher. There were 26 patients suffering from bone pain, with average numerical rating scales(NRS) score of 3.7. In addition, there were 107 patients being resistant to hormone therapy, with average age of 73 years (range 56-83 years), and median PSA of 84.5 ng/ml (range 12.4-490.2 ng/ml), including 32 patients (29.9%) with a Gleason score of 7 or lower, and 75 patients (70.1%) with a Gleason score of 8 or higher. Among them, there were 75 patients suffering from bone pain, with average NRS score of 5.4. All patients received continuous hormone therapy combined with docetaxel (at a dose of 75 mg per square meter of body-surface area every 3w, plus prednisone 5 mg twice a day), and PSA progression-free survival (PSA-PFS), NRS score, pain relief, and adverse events were analyzed. Additional analysis of the correlation between PSA-PFS and subgroups with age, PSA level and Gleason score were performed.Results:For patients with metastatic hormone sensitive prostate cancer (mHSPC), 6 (6.2%) cases only received 1-2 cycles of chemotherapy due to different reasons, and the others received 3-6 cycles(average 4.7)with the median follow-up of 15 months. Of patients who received ≥3 cycles, there were 36 cases presenting PSA progression, with the median PSA-PFS of 22 months, average NRS score decline from 3.9 to 3.0, and pain relief rate of 72.0%(18/25). For patients with metastatic castration-resistant prostate cancer (mCRPC), 9 (8.4%)cases only received 1-2 cycles of chemotherapy, and the others received 3-14 cycles (average 5.6). Of patients who received≥3 cycles, there were 51 cases with PSA progression, with the median PSA-PFS of 11 months, average NRS score decline from 5.6 to 4.4, and pain relief rate of 48.6%(35/72). Subgroup analysis showed a significant correlation between PSA level and PSA-PFS for patients with mCRPC( P=0.026). Age or Gleason score was not significantly correlated to PSA-PFS in mHSPC or mCRPC( P>0.05). For patients with mHSPC, grade 3 or 4 neutropenia occurred in 17 cases(17.5%), nausea and vomiting in 27 cases(27.8%), and fatigue in 25 cases(25.8%). For patients with mCRPC, grade 3 or 4 neutropenia occurred in 24 cases (22.4%), nausea and vomiting in 34 cases(31.8%), and fatigue in 26 cases(24.3%). Allergic reaction and sensory neuropathy toxicity were occasional. Conclusion:Efficacy of docetaxel plus hormone therapy was confirmed in metastatic prostate cancer and adverse events were tolerable.

Effect of FGL1 on invasion and migration of lung adenocarcinoma cells induced by docetaxel and its mechanism / 中国药理学通报

Aim To investigate the effect of fibrinogen-isomeric protein 1 (FGL1) on the invasion and migration ability of docetaxel induced lung adenocarcinoma cells and the related mechanism. Methods Gene expression of FGL1 in tumors was obtained from TCGA database, and the Kaplan Meier Plotter database was used to analyze the sample information in the GEO database and draw the survival curve. The PC-9 and A549 of human lung adenocarcinoma cells were selected as the research object. FGL1 expression was knocked down by small interfering RNA (siRNA). Transwell method and cell scratch test were employed to detect cell invasion and migration; Western blot was applied to detect the expression level of E-cadherin and N-cadherin proteins. Results Compared with normal tissues, FGL1 expression was significantly up-regulated in lung adenocarcinoma. Survival analysis showed that the overall survival of patients with high FGL1 expression was shorter than that of patients with low expression. The migration and invasion ability of PC-9 and A549 cells significantly decreased after knockdown FGL1 expression. Under the same doze of docetaxel, decreased expression of FGL1 significantly inhibited the invasion and migration ability of lung adenocarcinoma PC-9 and A549 cells. FGL1 silencing combined with docetaxel significantly down-regulated N-cadherin protein expression and up-regulated E-cadherin protein expression in lung adenocarcinoma cells. Conclusions FGL1 is highly expressed in lung adenocarcinoma and is related to patient survival and prognosis. FGL1 can enhance the ability of docetaxel to inhibit the invasion and migration of lung adenocarcinoma PC-9 and A549 cells by blocking the EMT process.

Neoadjuvant chemo-hormonal therapy for very-high-risk locally advanced prostate cancer: a large cohort retrospective multi-institutional study / 中华泌尿外科杂志

Objective:To investigate the clinical efficacy of neoadjuvant chemo-hormonal therapy(NCHT)followed by radical prostatectomy(RP) plus extended pelvic lymphadenectomy for very-high-risk locally advanced prostate cancer.Methods:The data of 327 cases of very-high-risk locally advanced prostate cancer treated in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, The Second Hospital of Tianjin Medical University, and The Third Affiliated Hospital of Sun Yat-sen University from December 2014 to July 2019 were retrospectively analyzed. Patients were divided into two groups according to treatment regimens: the RP group (direct RP + extended pelvic lymphadenectomy 4-6 weeks after the biopsy of prostate) and the NCHT group (4-6 cycles of NCHT prior to RP). There were 171 cases in RP group and 156 cases in NCHT group, respectively. In the RP group, the median age was 67 (ranging 44-83)years. The median PSA at diagnosis was 27.24 (ranging 4.55-207.00) ng/ml. Patients’numbers of clinical T 2, T 3a, T 3b, T 4 stage were 13, 85, 57, 16, respectively, and clinical N 1, N 0 stage were 33 and 138, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 5, 35, 41, 51, 39, respectively. In the NCHT group, The median age was 67 years, ranging 46-78 years. The median PSA at diagnosis was 72.09(ranging 4.08-722.95)ng/ml. Patients’ numbers of clinical T 2, T 3a, T 3b, T 4 stage were 11, 47, 58, 40, respectively, and clinical N 1, N 0stage were 76 and 80, respectively. Patients’numbers of ISUP grade groups of 1, 2, 3, 4, 5 were 1, 11, 33, 43, 68, respectively. At baseline, the NCHT group showed higher PSA, higher ISUP grade, and more advanced clinical stage at diagnosis( P<0.05). The PSA, pathological down-staging rate, and positive surgical margin rate as well as the biochemical recurrence free survival(bRFS)were compared between the two groups. Results:After radical prostatectomy, compared with the RP group, the NCHT group had a higher proportion of patients achieving PSA<0.2 ng/ml at 6-week postoperative follow-up ( P<0.001), a higher pathologic tumor stage down-staging rate ( P<0.001), a higher ISUP down-grading rate ( P<0.001), and a lower positive surgical margins rate ( P<0.001). In addition, 10.9% of the NCHT group achieved pT 0 or minimal residual disease in postoperative pathology exams. Eighty-three patients (48.5%) in the RP group and 125 patients (80.1%) in the NCHT group achieved undetectable PSA after surgery and entered further analysis for bRFS, which showed NCHT group had significantly longer bRFS (19.46 months vs. 6.35 months). NCHT significantly reduced the risk for biochemical recurrence in locally advanced prostate cancer patients( HR=0.278, 95% CI 0.198-0.390, P<0.001). Such a reduce in risk for biochemical recurrence was seen in all subgroups( P<0.001). Conclusions:NCHT might improve surgical outcomes as well as bRFS in very-high-risk locally advanced prostate cancer patients.

Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer / 北京大学学报(医学版)

OBJECTIVE@#To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC).@*METHODS@#From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m2, and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed.@*RESULTS@#Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range.@*CONCLUSION@#This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.

Clinical Analysis of Docetaxel Combined with PD-1/PD-L1 Inhibitor in Second-line Treatment of Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Programmed cell death 1 or programmed cell death ligand 1 inhibitor (PD-1/PD-L1 inhibitor) and docetaxel, as the standard second-line treatments of advanced non-small cell lung cancer (NSCLC) patients, have limited effects. There are few studies on whether docetaxel combined with PD-1/PD-L1 inhibitor can increase the efficacy and make patients better benefit. The aim of this study is to evaluate the efficacy and safety of docetaxel combined with PD-1/PD-L1 inhibitor for the second-line treatment of stage IV NSCLC patients.@*METHODS@#Stage IV NSCLC patients (n=118) who received treatment at Shandong Cancer Hospital between October 1, 2018, and December 31, 2020, were retrospectively analyzed. They were divided into observation group (n=69) and control group (n=49) according to different treatment plan. Observation group was given docetaxel plus PD-1/PD-L1 inhibitor, while control group was given PD-1/PD-L1 inhibitor. The clinical curative effect and the incidence of adverse reactions of grade 3 and above were compared between the two groups.@*RESULTS@#The disease control rate (DCR) was higher in the observation group (89.9%) than that in the control group (73.5%) (P=0.019), and the objective response rate (ORR) showed no significant difference between observation group (24.6%) and control group (16.3%) (P=0.276). Till June 22, 2021, the 1-year PFS rate showed no difference between observation group (16.5%) and control group (7.7%) (P=0.205). During the treatment period, the adverse reactions of the two groups were mostly grade 1 to 2, and could be tolerated. The incidence of bone marrow suppression in observation group was higher than that in the control group (P<0.05), and the remaining adverse reactions were not statistically different from control group. Cox regression analysis showed that performance status (PS) (P=0.020) and age (P=0.049) were independent prognostic factors for the effect of docetaxel combined with PD-1/PD-L1 inhibitor.@*CONCLUSIONS@#The second-line treatment with docetaxel plus PD-1/PD-L1 inhibitor in patients with stage IV NSCLC can improve the DCR and prolong the PFS, and the adverse reactions are tolerable.

Effects of silencing HMGB1 combined with docetaxel chemotherapy on the proliferation and apoptosis of prostate cancer cells and its action mechanism / 中华男科学杂志

Objective@#To investigate the effect of silencing the high-mobility group box-1 protein (HMGB1) combined with docetaxel (DTX) on the proliferation and apoptosis of PCa cells and its possible action mechanism.@*METHODS@#The expression of HMGB1 mRNA in different PCa cell lines and normal prostatic epithelial cells was detected by RT-qPCR. The PC-3 cells were transfected with different HMGB1 small interfering RNAs (si-HMGB1, si-HMGB1-2 and si-HMGB1-3), and the silencing effect was detected. The effects of different concentrations of DTX on the proliferation of the PC-3 cells was determined by MTT. Then the PC-3 cells were randomly divided into five groups: control (conventional culture), si-HMGB1-NC (si-HMGB1-NC transfection), si-HMGB1 (si-HMGB1-3 transfection), DTX (20 nmol/L DTX), and si-HMGB1+DTX (si-HMGB1-3+20 nmol/L DTX transfection), followed by measurement of the survival rate of the cells by MTT, their apoptosis rate by flow cytometry, and the expressions of HMGB1, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) proteins in different groups by Western blot.@*RESULTS@#The expression of HMGB1 mRNA in the PC-3 cells was the highest and the lowest after transfection with si-HMGB1-3. DTX inhibited the proliferation of the PC-3 cells at various concentrations. Compared with the control group, the si-HMGB1 and DTX groups showed significantly decreased A values, cell survival rates and HMGB1 and Bcl-2 expressions, but increased cell apoptosis rates and Bax expressions (P < 0.05). In comparison with the si-HMGB1 and DTX groups, the si-HMGB1+DTX group exhibited a remarkably decreased A value, cell survival rate and Bcl-2 expression, but increased cell apoptosis and Bax expression. The expression of the HMGB1 protein was markedly lower in the si-HMGB1+DTX than in the DTX group (P < 0.05).@*CONCLUSIONS@#Silencing HMGB1 combined with DTX chemotherapy can inhibit the proliferation and promote the apoptosis of PCa cells, which may be attributed to its regulatory effect on the expressions of the Bcl-2 family-related proteins.、.

Stability，in vitro Release and Tissue Distribution of Docetaxel-dihydroartemisinin Conjugated Prodrug Self- assembled Nanoparticles / 中国药房

OBJECTIVE：To study the sta bility，in vivo release characteristics and tissue distribution of docetaxel （DTX）- dihydroartemisinin（DHA）conjugated prodrug self-assembled nanoparticles （DTX-S-S-DHA NPs ）. METHODS ：HPLC method was adopted to analyze DTX-S-S-DHA in vitro . The phycial and long-term stability of DTX-S-S-DHA NPs in mediums [water ， saline，phosphate buffer （PBS，pH 7.4）and RPMI 1640 medium] were investigated by using particle size ，polydispersity index （PDI）and encapsulation efficiency （EE）as evaluation indexes. The in vitro release characteristics of DTX-S-S-DHA released from DTX-S-S-DHA NPs was also investigated with small glass method ，using 30％ ethanol solution with or without 10 mmol/L dithiothreitol（DTT）as medium. The small live animal imager was adopted to investigate the tissue distribution and tumor targeting capability of DiR-labeled DTX-S-S-DHA NPs （DTX-S-S-DHA/DiR NPs ）in breast cancer bearing mice. RESULTS ：In stability test，there was no statistical difference in particle size ，PDI and EE of DTX-S-S-DHA NPs incubated in water ，normal saline ，PBS and RPMI 1640 medium for 24 h. When stored at 4 ℃，with the increase of storage time ，the particle size of DTX-S-S-DHA NPs in normal saline gradually increased ，while those in PBS gradually decreased ；EE of both gradually decreased to less than 75％， but there was no significant change in particle size ，PDI and EE of DTX-S-S-DHA NPs in water and RPMI 1640 medium. In the in vitro release experiments ，DTX-S-S-DHA in DTX-S-S-DHA NPs was not released in the release medium containing 10 mmol/L DTT；at 24 h，the cumulative release rate of DTX-S-S-DHA released from DTX-S-S-DHA NPs in release medium without DTT was about 83％，which was in line with first-order kinetic model. In tissue distribution test ，the distribution of DTX-S-S-DHA/DiR NPs in tumor sites of mice was significantly more than in other tissues （heart，liver，spleen，lung and kidney ）. CONCLUSIONS ： DTX-S-S-DHA NPs show good physical stability in different mediums ，especially have good long-term stability in water and RPMI ； 1640 medium；they can quickly release the parent drug in the reduction environment and has good tumor targeting.