Journal of Chemotherapy最新文献

Purpose: The study aimed to compare the impact of combination and monotherapy on mortality, antibiotic consumption using 'Days of Therapy (DOT)', and antibiotic-related adverse events in patients with methicillin-susceptible S. aureus (MSSA) bacteraemia.

Methods: This retrospective study included all adult patients (>18 years) with MSSA bacteraemia who received either monotherapy (beta-lactam alone) or combination therapy (beta-lactam plus teicoplanin or daptomycin or linezolid) between 2018 and 2023. Mortality, antibiotic consumption, and factors predicting mortality were analysed. Groups were compared for 30-d mortality with survival analysis. Logistic regression models were used to identify risk factors for mortality. Antibiotic consumption was calculated by DOT.

Results: Among 395 patients screened, 185 patients who had an MSSA bacteraemia received either monotherapy (n = 73, 39.5%) or combination therapy (n = 112, 60.5%). The 30-d mortality rate was similar between groups (%15.1 vs. 21.4, P = 0.280). Time to bacterial clearance was also similar (median (IQR): 4 (3-7) vs. 4 (3-7) d, P = 0.699). DOT per 1000 patient days was significantly higher in the combination therapy group than in the monotherapy group (median, IQR: 1420, 827-1836 vs. 933, 732-1000), P < 0.001). The 30-d mortality rate was 18.9% (n = 35/185), and the PITT bacteraemia score was the only independent predictor of mortality (median, IQR: 1506, 1.264-1.794, P < 0.001).

Conclusions: Our findings indicate that combination therapy does not confer a survival benefit over monotherapy in patients with MSSA bacteraemia. However, combination therapy was associated with a significant increase in antibiotic consumption. Therefore, our results do not support the routine use of combination therapy for MSSA bacteraemia in this patient population.

Background: Well-differentiated (WDLPS) and dedifferentiated liposarcomas (DDLPS) are subtypes with distinct behaviors, often driven by CDK4 amplification. While CDK4/6 inhibitors such as palbociclib show promise in trials, real-world data are scarce.

Methods: We retrospectively analyzed 21 patients with advanced WDLPS or DDLPS treated with palbociclib monotherapy at 16 Turkish Oncology Group centers (2019-2022). Outcomes included progression-free survival (PFS), overall survival (OS), response, and safety.

Results: Median age was 51 years; 38.1% had WDLPS and 61.9% DDLPS. Median PFS was 5.3 months and OS 9.1 months. The objective response rate was 0%, but disease control was achieved in 57.1%. WDLPS and earlier-line use were associated with numerically longer OS. Adverse events occurred in 71.4%, most often anemia (52.4%) and neutropenia (33.3%).

Conclusion: Palbociclib showed modest activity with disease stabilization in some patients, highlighting the need for biomarker-driven and combination strategies.

The aim of this Phase 1, multicentre, open-label study was to evaluate the safety, tolerability and pharmacokinetics (PK) of abemaciclib administered at global recommended Phase 2 dose (RP2D) of 200 mg twice daily, combined with standard doses of abiraterone and prednisolone, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Dose-limiting toxicities (DLTs) were assessed for 28 days post-first dose. Six patients were treated, and all experienced at least one treatment-emergent adverse event (TEAE), mostly low grade; no Grade 4 or 5 TEAEs occurred. Diarrhoea was the most common TEAE (all events were Grade 1 except for one Grade 2). Three patients experienced serious adverse events (SAEs), leading to treatment discontinuation in two cases. The PK profile was consistent with non-Japanese patients, with no PK drug-drug interactions detected. The study confirms that the global RP2D of abemaciclib is suitable for Japanese patients with mCRPC treated with abiraterone and prednisolone.

To assess the efficacy and safety of capecitabine in treating advanced colon cancer. Patients with advanced colon cancer were randomized into three groups: control group (n = 50, daily dose 2,500 mg/m²), the medium-dose group (n = 50, daily dose 2,000 mg/m²), and the low-dose group (n = 50, daily dose 1,500 mg/m²) capecitabine for 4 cycles(12 weeks). Afterwards, the response rate, quality of life, and adverse reactions of the three groups were collected for comparison. Efficacy rates were 50%, 70%, and 72%, respectively, with the low-dose group showing the highest efficacy (χ2 = 6.424, p = 0.040); Quality of life comparison results indicated significant differences in physical function (F = 98.528, p < 0.001), role function (F = 123.418, p < 0.001), social function(F = 89.539, p < 0.001), emotional function (6 F = 77.295, p < 0.001), cognitive function (F = 83.529, p < 0.001), and overall quality of life (F = 99.528, p < 0.001) among the three groups, and the three groups returned consistent scores, with the low-dose group scoring highest. Incidence rates were 86.00%, 46.00%, 34.00%, with the control group having the highest rate (χ² = 16.505, p < 0.001). Capecitabine at a dosage of 1,500 mg/m² demonstrated a good therapeutic effect and improved the quality of life in patients with advanced colon cancer, with a lower incidence of adverse reactions. A prolonged treatment cycle with reduced dosage is suggested to further improve treatment outcomes and patient prognosis. Trial registration The study was registered on clicaltrials.gov 'NCT06246461' on 30/01/2024.

The rapid rise of nosocomial infections and the growing ineffectiveness of frontline antibiotics against Gram-negative bacteria (GNB) have put the healthcare sector under unprecedented stress. In this scenario, colistin, an antibiotic of the polymyxin class, has become the last resort treatment option. However, the unrestricted use of colistin in the preceding decades has led to the emergence of colistin-resistant (Col^R) bacterial strains. Unfortunately, comprehensive data on the prevalence of Col^R nosocomial pathogens in India are scarce. This study was conducted to address this information gap. A systematic review and meta-analysis were conducted to determine the prevalence of Col^R among the nosocomial GNB species in India and their geographical distribution. A systematic search of the online databases was performed and eligible studies meeting the inclusion criteria were used for qualitative synthesis. The combined event rate and 95% confidence interval were estimated using a forest plot with a random-effect model. Cochrane Q statistics and I² statistics were used to detect possible heterogeneity. From a total of 1865 retrieved records from 4 databases, 33 studies were included in the study. Among the most common nosocomial pathogens, Klebsiella pneumoniae showed a rate of Col^R at 16.1% (95% CI: 10.1 to 24.6), followed by Pseudomonas aeruginosa (13.3%) (95% CI: 9.1 to 19.2), Acinetobacter baumannii (10%) (95% CI: 7.5 to 13.2), and Escherichia coli (7.8%) (95% CI: 5.3 to 11.2). Interestingly, our analysis revealed that Enterobacter cloacae have the highest rate of Col^R at 27.9% (95% CI: 12.7 to 50.9). The results indicate that the prevalence of Col^R nosocomial pathogens vary among regions and over time; however, continuous monitoring, and sustained efforts are crucial to ensure the effectiveness of colistin antibiotic.

Hepatocellular carcinoma (HCC), as a malignancy derived from liver tissue, is typically associated with poor prognosis. Increasing evidence suggests a connection between pyrimidine metabolism and HCC progression. The purpose of this study was to establish a model applied to the prediction of HCC patients' overall survival. Transcriptomic data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) website. Pyrimidine metabolism-related genes (PMRGs) were collected from the Gene Set Enrichment Analysis (GSEA) website. Differential gene expression analysis was carried out on the HCC data, followed by an intersection of the differentially expressed genes (DEGs) and PMRGs. Subsequently, a prognostic model incorporating nine genes was established using univariate/multivariate Cox regression and Least absolute shrinkage and selection operator (LASSO) regression. Survival analysis demonstrated that the high-risk group defined by this model had considerably shorter overall survival than the low-risk group in both TCGA and Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic (ROC) analysis indicated the good predictive capability of the model. CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms revealed significantly higher levels of Macrophages M0 and lower levels of natural killer (NK)_cells in the high-risk group compared to the low-risk group. The immunophenoscore (IPS) and the tumor immune dysfunction and exclusion (TIDE) score demonstrated that the model could significantly differentiate patients who would be more suitable for immunotherapy. Moreover, the CellMiner database was utilized to predict anti-tumor drugs significantly associated with the model genes. Collectively, the potential prognostic significance of pyrimidine metabolism in HCC was revealed in this study. The prognostic model aids in evaluating the survival time and immune status of HCC patients.

The effectiveness of vonoprazan (VPZ)-based regimens in enhancing Helicobacter pylori (HP) eradication rates is promising. This study evaluated the clinical efficacy of 14-day VPZ-based triple therapy in obese patients infected with HP. A total of 200 obese patients with gastric disorders, confirmed to be HP-positive via gastroscopy and the ¹³C urea breath test, were retrospectively analyzed. Among them, 118 patients received the 14-day VPZ-based triple regimen (Study group), while 82 patients were treated with the traditional 14-day bismuth-containing proton pump inhibitor-based quadruple regimen (Control group). Baseline characteristics, pretreatment inflammatory indicators, lipid profiles, and gastrointestinal function indicators recorded. The two groups were compared for treatment efficacy, HP eradication rate, gastrointestinal function improvement, and incidence of adverse reactions. The Study group demonstrated a higher overall effective rate compared to the Control group, particularly in HP-strong positive obese patients. No significant differences were observed between the two groups for HP-positive obese patients in terms of total effective rate, HP eradication rate, gastrointestinal function improvement, or adverse reactions incidence. In conclusion, the 14-day VPZ-based triple regimen exhibited superior therapeutic efficacy, higher HP eradication rates, enhanced gastrointestinal function, and reduced adverse reactions in HP-strong positive obese patients, indicating improved overall efficacy and safety.

We conducted this meta-analysis to investigate neurological toxicities with poly (ADP-ribose) polymerase inhibitors (PARPis) in cancer patients. Databases were searched for randomized controlled trials (RCTs) from 1 January 2000 to 1 November 2023. Forty-six RCTs and 9529 patients were included. PARPis could increase the risk of all-grade headache [risk ratio (RR), 1.22; 95% confidence intervals (CI), 1.14-1.30; P < 0.00001], dizziness (RR, 1.40; 95% CI, 1.28-1.53; P < 0.00001), dysgeusia (RR, 1.93; 95% CI, 1.44-2.60; P < 0.0001) and insomnia (RR, 1.32; 95% CI, 1.09-1.60; P < 0.0001) in cancer patients. Headache was the most common neurological toxicity. Niraparib was associated with a higher risk of headache and insomnia, talazoparib with a higher risk of dizziness and rucaparib with a higher risk of dysgeusia. Breast cancer patients receiving PARPis have a higher risk of dysgeusia, while ovarian cancer patients are at an increased risk of insomnia. PARPis may increase the risk of mild to moderate neurological toxicities, but not severe ones.

Our study was carried out to define the efficacy of treatment with sequential chemotherapy lines in patients with epithelioid sarcoma (ES) at referral centres for sarcoma. From 1998 to 2023, 22 patients with ES were treated with chemotherapy and included in the analysis. The median age at the start of palliative treatment was 35 (20-68). The median follow-up was 22.1 months. In the first line, 13 patients (59%) received anthracycline-based chemotherapy and 6 (27%) high-dose ifosfamide. One patient (4.5%) achieved PR, 15 (68%) SD, and 6 (32%) PD as the best response. The median progression-free survival (PFS) in the first line was 6.4 months (95% CI: 3.02-12.9), but 9.7 months (95% CI: 4.37-NR) for chemotherapy based on anthracycline, indicating a more favourable PFS (p = 0.027). Twenty (90%) patients received second-line treatment, and eleven received third-line chemotherapy. The median OS from the start of first-line palliative chemotherapy was 22.1 months (95% CI: 10.5-41.4) and 14.7 months from the beginning of the second line. Perioperatively, patients pretreated with anthracycline had a median PFS of 2.9 months in the M1 setting. Second-line long-time responses were achieved with pazopanib or vincristine with actinomycin D. Despite chemoresistance, an advantage associated with anthracycline-based chemotherapy was confirmed in the ES cohort. Poor responses underscore the need for further research on targeted therapies for ES. Second-line chemotherapy or clinical trials should be offered to all eligible patients.

Acquired chemoresistance remains a significant challenge in the clinics as most of the treated cancers eventually emerge as hard-to-treat phenotypes. Therefore, identifying chemoresistance targets is highly warranted to manage the disease better. In this study, we employed a label-free LC-MS/MS-based quantitative proteomics analysis to identify potential targets and signaling pathways underlying acquired chemoresistance in a sub-cell line (A549DR) derived from the parental lung adenocarcinoma cells (A549) treated with gradually increasing doses of doxorubicin (DOX). Our proteomics analysis identified 146 upregulated and 129 downregulated targets in A549DR cells. The KEGG pathway and Gene ontology (GO) analysis of differentially expressed upregulated and downregulated proteins showed that most abundant upregulated pathways were related to metabolic pathways, cellular senescence, cell cycle, and p53 signaling. Meanwhile, the downregulated pathways were related to spliceosome, nucleotide metabolism, DNA replication, nucleotide excision repair, and nuclear-cytoplasmic transport. Further, STRING analysis of upregulated biological processes showed a protein-protein interaction (PPI) between CDK1, AKT2, SRC, STAT1, HDAC1, FDXR, FDX1, NPC1, ALDH2, GPx1, CDK4, and B2M, proteins. The identified proteins in this study might be the potential therapeutic targets for mitigating DOX resistance.