Journal of Chemotherapy最新文献

{"title":"Vancomycin loading dose individualization in a population of obese patients undergoing haemodialysis based on population pharmacokinetic model.","authors":"Lucie Polášková, Jan Miroslav Hartinger, Irena Murínová, Pavel Michálek, Ondřej Slanař, Martin Šíma","doi":"10.1080/1120009X.2024.2367937","DOIUrl":"10.1080/1120009X.2024.2367937","url":null,"abstract":"<p><p>This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2-52.9 kg/m² were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6-84.2) L and 0.86 (0.79-0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50-60, 60-70, 70-80, 80-85 and >85 kg, respectively.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"121-129"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atorvastatin attenuates intestinal mucositis induced by 5-fluorouracil in mice by modulating the epithelial barrier and inflammatory response.","authors":"Kátia Duarte Vital, Luiz Octavio Pires, Bruno Gallotti, Janayne Luihan Silva, Luís Cláudio Lima de Jesus, Jacqueline Isaura Alvarez-Leite, Ênio Ferreira, Vasco Ariston de Carvalho Azevedo, Flaviano Santos Martins, Valbert Nascimento Cardoso, Simone Odília Antunes Fernandes","doi":"10.1080/1120009X.2024.2345027","DOIUrl":"10.1080/1120009X.2024.2345027","url":null,"abstract":"<p><p>Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as <i>Tlr4, MyD88, NF-κB, Tnf-a, Il1β,</i> and <i>Il6</i> dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and <i>ZO-1</i> and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"175-192"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential role of genetic polymorphisms in neoadjuvant chemotherapy response in breast cancer.","authors":"Om Elez Bouhniz, Abderraouf Kenani","doi":"10.1080/1120009X.2024.2330241","DOIUrl":"10.1080/1120009X.2024.2330241","url":null,"abstract":"<p><p>Chemoresistance leads to treatment failure, which can arise through different mechanisms including patients' characteristics. Searching for genetic profiles as a predictor for drug response and toxicity has been extensively studied in pharmacogenomics, thus contributing to personalized medicine and providing alternative treatments. Numerous studies have demonstrated significant evidence of association between genetic polymorphisms and response to neoadjuvant chemotherapy (NAC) in breast cancer. In this review, we explored the potential impact of genetic polymorphisms in NAC primary resistance through selecting a specific clinical profile. The genetic variability within pharmacokinetics, pharmacodynamics, DNA synthesis and repair, and oncogenic signaling pathways genes could be predictive or prognostic markers for NAC resistance. The clinical implication of these results can help provide individualized treatment plans in the early stages of breast cancer treatment. Further studies are needed to determine the genetic hosts of primary chemoresistance mechanisms in order to further emphasize the implementation of genotypic approaches in personalized medicine.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"97-111"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the prognostic effect of pyrotinib plus trastuzumab and chemotherapy different lines therapy in HER2-positive advanced breast cancer.","authors":"Yangqingqing Zhou, Hui Wang, Jiao Yang, Fan Wang, Danfeng Dong, Xiaoai Zhao, Le Wang, Ruiyuan He, Zhiping Ruan, Jin Yang","doi":"10.1080/1120009X.2024.2335714","DOIUrl":"10.1080/1120009X.2024.2335714","url":null,"abstract":"<p><p>This study aimed to compare the efficacy of pyrotinib, trastuzumab combined with chemotherapy with different lines therapy in human epidermal growth factor receptor 2- (HER2-) positive advanced breast cancer (ABC) and analyze the factors affecting the prognosis. A total of 84 patients with median age of 49 year-old. The mPFS of patients receiving first-line pyrotinib plus trastuzumab and chemotherapy was the longest (11 months) compared with second- and third line patients (<i>p</i> = 0.106). The objective response rate (ORR) and disease control rate (DCR) of the total population were 33.3% and 82.1% respectively. Subgroup analysis suggested that using pyrotinib plus trastuzumab and Albumin-bound paclitaxel was not inferior to combine with Vinorelbine in regards of PFS. Histological grade (OR: 0.233[0.069 ∼ 0.781], <i>p</i> = 0.018) and tumor location (OR: 0.286[0.087 ∼ 0.942], <i>p</i> = 0.040) were independent factors influencing the ORR. Multivariate cox analysis showed that Ki-67 was independently associated with increased risk of progression (HR: 1.843[1.044-3.254], <i>p</i> = 0.035). The most common adverse events were diarrhea (17.9%) and neutropenia (11.9%). In the first-, second- and third-line treatment, pyrotinib plus trastuzumab and chemotherapy is effective and safe. Pyrotinib and trastuzumab combined with Albumin-bound paclitaxel may be a potential ideal treatment plan for HER2-positive advanced breast cancer.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"135-145"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19.","authors":"Roberta Maria Antonello, Davide Marangoni, Filippo Ducci, Anna Barbiero, Tommaso Manciulli, Lucia Graziani, Nicoletta Di Lauria, Lorenzo Menicacci, Lorenzo Paci, Benedetta Sordi, Lorenzo Zammarchi, Alessandro Morettini, Sara Tomassetti, Gian Maria Rossolini, Alessandro Bartoloni, Michele Spinicci","doi":"10.1080/1120009X.2024.2367935","DOIUrl":"10.1080/1120009X.2024.2367935","url":null,"abstract":"<p><p>The management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (<i>n</i> = 4), nirmatrelvir/ritonavir plus remdesivir (<i>n</i> = 4) or remdesivir plus molnupiravir (<i>n</i> = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"130-134"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of metronomic capecitabine and letrozole in metastatic hormone receptor positive, HER2 negative breast cancer: a randomized phase II trial.","authors":"Hamdy A Azim, Mariam A Saleh, Passant Essam Eldin, Ahmed A M Abdelhafeez, Mohamed Hassan, Loay Kassem","doi":"10.1080/1120009X.2024.2342741","DOIUrl":"10.1080/1120009X.2024.2342741","url":null,"abstract":"<p><p>First line endocrine therapy is the gold standard for advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Adding CDK4/6 inhibitors has improved progression free survival. Metronomic Capecitabine has proven to be safe to combine with endocrine therapy with promising efficacy. We conducted a phase II randomized, open label, single centre clinical trial on patients with metastatic ER positive and HER 2 negative breast cancer. Eligible patients were randomized (1:1) to arm A: metronomic dose of capecitabine (500 mg/m² BID) combined with letrozole (2.5 mg OD) or arm B: letrozole single agent. The primary endpoint was progression free survival. The study was terminated early due to poor accrual and 60 eligible patients out of the planned 204 were randomized. This clinical trial is registered on ClinicalTrials.gov (MD-127-2019, NCT04571437). Between February 2019 and April 2022, 60 patients were randomized. This is the first report of the study, after a median follow-up of 18.6 months. The median age at diagnosis was 47 years with only 41.7% of patients post-menopausal. Half of our patients had bone-only disease, 45% had visceral metastasis (liver and lung) and 63% presented with endocrine sensitive disease. The estimated median PFS for the whole population was 16.2 months. Median PFS for capecitabine arm was 17.7 months versus 14.6 months for letrozole alone (<i>p</i> = 0.078). Overall response rate was 70% for capecitabine/letrozole arm and 56.6% for letrozole only. Clinical benefit rate was 90% in the capecitabine/letrozole arm versus 73.3% in the letrozole arm. Overall survival data is still immature after this short follow up duration. Adverse event assessment showed acceptable all grade and high grade toxicity profile consistent with the established adverse events of both capecitabine and letrozole. Anaemia (28.3%) and hand & foot syndrome (43.8%) were significantly more common in the capecitabine/letrozole arm. Capecitabine combined with letrozole have showed a trend towards improvement in progression free survival with potential more benefit to certain sub-groups and the combination showed acceptable safety profile consistent with the established known safety profile of both letrozole and capecitabine.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"159-167"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare immune-related adverse effect of pembrolizumab: pulmonary hypertension.","authors":"Caner Acar, Gökhan Sahin, Haydar Çagatay Yüksel, Burçak Karaca","doi":"10.1080/1120009X.2024.2349858","DOIUrl":"10.1080/1120009X.2024.2349858","url":null,"abstract":"<p><p>Pembrolizumab is an immune checkpoint inhibitor that acts <i>via</i> PD-1 blockade. Recent studies have shown its effectiveness in treating various solid organ tumours. However, unlike cytotoxic chemotherapeutic agents, pembrolizumab may cause immune-related adverse effects. These immune-related adverse effects are generally mild, although patients who experience grade-three or higher side effects may require hospitalisation. In particular, cardiopulmonary side effects are associated with high mortality rates. We report the case of a 24-year-old female patient with alveolar soft part sarcoma accompanied by rare and difficult-to-treat pulmonary hypertension induced by pembrolizumab.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"193-198"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical scoring model for predicting cefotaxime-resistance in <i>Klebsiella pneumoniae</i> bacteremia: development and validation based on portal of entry.","authors":"Hyoung-Tae Kim, Cheon-Hoo Jeon, Si-Ho Kim, Yu Mi Wi","doi":"10.1080/1120009X.2024.2357052","DOIUrl":"10.1080/1120009X.2024.2357052","url":null,"abstract":"<p><p>We developed a prediction model for cefotaxime resistance in patients with <i>K. pneumoniae</i> bacteremia. Adult patients with <i>K. pneumoniae</i> bacteremia were grouped into derivation (from March 2018 to December 2019) and validation (from January 2020 to August 2020) cohorts. The prediction scoring system was based on factors associated with cefotaxime resistance identified by the logistic regression model. A total of 358 patients were enrolled (256 for derivation, 102 for validation). In the multivariable analysis, age ≥65 years, hospital-acquired infection, prior antimicrobial use, and an updated Charlson comorbidity index ≥3 points were associated with cefotaxime resistance in the derivation cohort. When each variable was counted as 1 point, the values of the area under the curve were 0.761 in the derivation and 0.781 in the validation cohorts. The best cutoff value using the Youden index was ≥2 with 73.6% sensitivity and 67.5% specificity. Our simple scoring system favorably predicted cefotaxime resistance.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"112-120"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical benefit of PD-1/PD-L1 inhibitors for poor performance status patients with advanced non-small cell lung cancer.","authors":"Junji Koyama, Masahiro Morise, Ichidai Tanaka, Sho Hori, Reiko Matsuzawa, Sachiko Ozone, Akihiro Matsushita, Masaki Matsuo, Shuichi Asano, Taro Tanaka, Koichiro Shima, Tomoki Kimura, Koji Sakamoto, Yasuhiro Kondoh, Naozumi Hashimoto","doi":"10.1080/1120009X.2025.2481349","DOIUrl":"10.1080/1120009X.2025.2481349","url":null,"abstract":"<p><p>The benefit of programmed cell death protein-1 (PD-1)/programmed cell death protein ligand-1 (PD-L1) inhibitors remains unclear in non-small cell lung cancer (NSCLC) patients with poor performance status (PS). In the current multi-centre retrospective cohort study, advanced or recurrent NSCLC patients treated with PD-1/PD-L1 inhibitors were enrolled. Of the 219 patients enrolled, 44 had PS 2-4. The objective response rate (ORR) of patients with PS 2-4 in 1^st line was 33%. Among 1^st line group, median progression-free survival (PFS) in patients with PS 2 was significantly longer compared to that in patients with PS 3-4 (15.3 months vs. 0.9 months, P = 0.039, Log-rank test). Among previously treated patients, the ORR of patients with PS 2-4 was only 4%, and PFS and overall survival was poor even in patients with PS 2. PD-1/PD-L1 inhibitors can be an option for PS 2 NSCLC patients in 1^st line setting.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-10"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent inhibition of FLT3 and sphingosine kinase-1 triggers synergistic cytotoxicity in midostaurin resistant FLT3-ITD positive acute myeloid leukemia cells via blocking FLT3/STAT5A signaling to induce apoptosis.","authors":"Melisa Tecik, Aysun Adan","doi":"10.1080/1120009X.2025.2478340","DOIUrl":"https://doi.org/10.1080/1120009X.2025.2478340","url":null,"abstract":"<p><p>The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most frequent mutations observed in acute myeloid leukemia (AML) which contributes to disease progression and unfavorable prognosis. Midostaurin, a small FLT3 inhibitor (FLT3I), is clinically approved. However, patients generally possess acquired resistance when midostaurin used alone. Shifting the balance in the sphingolipid rheostat toward anti-apoptotic sphingosine kinase-1 (SK-1) or glucosylceramide synthase (GCS) is related to therapy resistance in cancer, however, their role in midostaurin resistant FLT3-ITD positive AML has not been previously investigated. We generated midostaurin resistant MV4-11 and MOLM-13 cell lines which showed increased IC₅₀ values compared to their sensitive partner cells. SK-1 is overexpressed in resistant cells while GCS remains unchanged. Subsequent pharmacological targeting of SK-1 in resistant cells decreased SK-1 protein level, inhibited cell proliferation and showed additive or synergistic effect on cell growth, as confirmed by the Chou-Talalay combination index, and induced G0/G1 arrest (PI staining by flow cytometry). Cotreatment (SKI-II plus midostaurin) triggered apoptosis <i>via</i> phosphatidylserine exposure (annexin V/PI double staining). Mechanistically, induction of the intrinsic pathway of apoptosis was confirmed as increased activating cleavages of caspase-3 and PARP and increased Bax/Bcl-2 ratios. Activating phosphorylations of FLT3 (at tyrosine residue 591) and STAT5A (at tyrosine residue 694) dramatically inhibited in resistant cells treated with the combination. In conclusion, midostaurin resistance could be reversed by dual SK-1 and FLT3 inhibition in midostaurin resistant AML cell lines, providing the first evidence of a novel treatment approach to re-sensitize FLT3-ITD positive AML.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-17"},"PeriodicalIF":1.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}