Journal of Chemotherapy最新文献

Trastuzumab is primarily utilized in the treatment of patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. This study aimed to investigate the incidence of cardiac toxicity associated with trastuzumab in HER2-positive breast cancer patients at Iran Hospital in 2023, as well as the factors influencing this toxicity. In this cross-sectional study, 200 patients diagnosed with HER2-positive breast cancer and receiving trastuzumab were included. The criteria for heart failure in this study were defined as an ejection fraction (EF) of less than 50% or a decrease of greater than 10% in EF. Descriptive statistics, the chi-square statistical test, Fisher's exact test, and logistic regression analyses were employed to assess the variables. A p-value of less than 0.05 was deemed statistically significant. The mean age of the participants was 51.5 ± 2.5 years. The odds ratio (OR) for the variable of anthracyclines was 1.3 (95% CI: 1.2-1.4); for opium use, the OR was 2.7 (95% CI: 0.9-8.5); for diabetes, the OR was 2.7 (95% CI: 1.2-5.9); for ischemic heart disease, the OR was 3.5 (95% CI: 1.6-7.7); and for hypertension, the OR was 4.8 (95% CI: 2.1-10.7). The OR for obesity was 1.45 (95% CI: 1.01-2.18), and the OR for age was 1.10 (95% CI: 1.01-1.12). No statistically significant association was found between opium use and cardiotoxicity (p = 0.07). This research contributes to the identification of factors that may predict responses to anthracyclines and the potential for cardiotoxicities. Ultimately, this information could inform the development of more personalized treatment strategies.

We review the case of a 58-year-old female on extracorporeal membrane oxygenation (ECMO) support diagnosed with invasive pulmonary aspergillosis (IPA). Intravenous isavuconazole was started, requiring dose escalation to achieve isavuconazole trough concentration (ISA-Cmin) within the therapeutic range (2.5-5.0 μg/mL). For more than 4 months, she maintained a dose of 200 mg q12h, with a median ISA-Cmin of 3.4 (interquartile range [IQR]: 3.1-4.9) µg/mL. Throughout this interval, 17 assessments of ISA-Cmin were performed (weekly). Of these, 82% (14/17) were within the therapeutic range, with an intra-individual variability of 36.8%. Although no signs of hepatotoxicity were observed, she experienced short-term gastrointestinal adverse events related to potential isavuconazole over-exposure (ISA-Cmin > 5.0 μg/mL). ECMO circuit changes did not appear to affect ISA-Cmin. She was not obese (IMC ≈ 25 kg/m²) and did not require other extracorporeal therapy, but hypoalbuminemia may have contributed to an increase in unbound isavuconazole fraction and consequently its clearance.

Polymer-based nanoparticles (PNPs) are emerging as a cornerstone in cancer therapy due to their ability to enhance drug solubility, improve pharmacokinetics and achieve precise tumor targeting. Nanoparticles, encompassing liposomes, dendrimers, and metallic particles, include typical characteristics such as improved surface area, regulated release and the capacity to encapsulate diverse therapeutic compounds augmenting the pharmacokinetics and bioavailability of anticancer drugs. Recent studies demonstrate drug loading efficiencies of 80-90%, circulation half-life extensions of 2-5 fold, and tumor accumulation improvements of 3-10 times compared to free drugs. FDA-approved formulations such as Abraxane^® (albumin-bound paclitaxel) and clinical candidates like Genexol-PM^® (polymeric micelles) highlight the translational relevance of PNPs. This review consolidates advancements in polymeric nanocarriers, including nanospheres, nano-capsules and hybrid composites, while addressing limitations in regulatory approval and personalized oncology integration. This study shows that nanoparticle-based cancer therapeutics hold immense potential to improve treatment efficacy and patient outcomes in clinical oncology.

To promote the accurate administration of linezolid, this study aimed to evaluate its dosage regimens in critically ill patients with varying renal functions. This evaluation was based on a combined analysis of pharmacokinetic (PK), pharmacodynamic (PD), and toxicodynamic (TD) indices. The percentage of therapeutic target attainment (PTTA) was used as the index for PK/PD/TD, defined as simultaneously meeting two PK/PD criteria (AUC_0-24h/MIC ≥ 100 and C_ss between 2.6-7.8 mg/L) and adjusted for toxicity probability, with MICs ranging from 0.5 to 8 mg/L. The recommended doses of linezolid for patients: 600 mg every 12 h for normal renal function or mild renal impairment, 300 mg every 12 h for severe renal impairment, 450 mg every 12 h for moderate renal impairment, and 600 mg every 8 h for supra-normal renal function. In conclusion, specific dosing regimens should be adopted for patients with varying renal functions, combined with therapeutic drug monitoring, to ensure the safety and efficacy of linezolid.

Anti-tumor drugs cause hand-foot syndrome through a variety of pathogenic mechanisms. Some chemotherapeutic medications that can cause HFS include 5FU, doxorubicin, capecitabine, high dose cytarabine, and others. These medications each have a unique mechanism resulting in HFS. The histopathological characteristics, clinical manifestations, and variations in gender, ethnicity, or genetic makeup might also impact the development of HFS as an adverse drug reaction. Even though the disease might not become life-threatening, it is nevertheless vital to manage it with therapeutic interventions or by withholding the medication in order to enhance the patient's outcome. Current developments in pharmacological and non-pharmacological therapeutic approaches for managing symptoms also emphasis the same.

Teicoplanin is a glycopeptide antibiotic with a long elimination half-life (50 hours) that allows administration thrice a week, though it is approved for daily use. The aim of this retrospective, single-arm study is to assess the clinical outcome of using thrice-weekly teicoplanin (TWT) as outpatient parenteral antibiotic therapy (OPAT) for deep (DSIs) and non-deep-seated infections (NDSIs). We included 37 outpatients (25 with DSIs and 12 with NDSIs) treated with TWT between 01/2021 and 10/2023. The outcome was favorable in 78% of them (80% with DSI, 75% with NDSIs) and Therapeutic drug monitoring (TDM) was performed in all cases. 8 patients required dosage modification because of inadequate trough levels; they were younger and had a higher creatinine clearance. 6/37 patients experienced adverse events, mostly skin rash (4/6). TWT can be a good option for OPAT; its pharmacokinetic reduces the number of hospital accesses and TDM permits to tailor the dosage.

This study aimed to evaluate the efficacy and prognostic factors of GEMOX (gemcitabine and oxaliplatin) combined with Tislelizumab in patients with advanced Gallbladder cancer (GBC). 150 patients with stage III-IV GBC were divided into two groups: 88 received GEMOX alone, and 62 received GEMOX combined with Tislelizumab. Clinical characteristics, treatment responses, progression-free survival (PFS), overall survival (OS) and adverse events were analysed. The combination group showed improved median OS (13.35 vs. 10.26 months, HR = 0.530, 95% CI: 0.357-0.786) and PFS (7.28 vs. 5.18 months, HR = 0.393, 95% CI: 0.278-0.555). The disease control rate (DCR) and objective response rate (ORR) were significantly higher in the combination group (DCR: 83.87% vs. 67.05%, P = 0.021; ORR: 40.32% vs. 20.45%, P = 0.008). Multivariate analysis identified TNM stage, CA19-9 status, CPS score, tumour diameter, and lesion multiplicity as independent prognostic factors for OS. GEMOX combined with Tislelizumab may improve survival outcomes in patients with advanced GBC.

Background: Erdheim-Chester Disease (ECD) is a rare, multisystemic histiocytosis with complex diagnosis and management. Case Presentation: We report a case of a 44-year-old male with ECD,confirmed by lung biopsy, presenting with persistent fatigue, intermittent low-grade fever, and bilateral interstitial lung disease. The patient initially received vincristine and prednisone, followed by maintenance therapy with 6-mercaptopurine, which resulted in both symptomatic and radiographic improvement. However, disease progression was noted after six months. Second-line therapy using a cytarabine-based regimen adapted from the Japan LCH Study Group-02 protocol achieved sustained remission for over two years. Conclusion: This case highlights the diagnostic complexity and therapeutic challenges of pulmonary-predominant ECD. It further underscores the potential utility of sequential cytotoxic chemotherapy as an alternative strategy in settings where targeted therapies, such as BRAF inhibitors, are not accessible. Future studies are needed to validate the role of such regimens in broader ECD populations.

Guidelines historically recommended mono-chemotherapy for the 1^st line treatment of elderly patients with non-small cell lung cancer (NSCLC) and poor performance status (PS). Nowadays, there is no clear indication whether chemo-immunotherapy (chemo-IO) combinations can be effectively delivered in this population. We collected induction chemotherapy data in consecutive patients with advanced NSCLC treated with carboplatin-based chemotherapy regimens plus pembrolizumab, to compute the received dose intensity (RDI) from standard regimens or patient-tailored regimens modified due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous and squamous NSCLC, treated with carboplatin-pemetrexed or carboplatin-paclitaxel doublets plus pembrolizumab, respectively. The majority of patients were aged ≥ 70 years (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an Eastern Cooperative Oncology Group (ECOG) - PS of 0, 1 and 2, respectively. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori modified regimens due to poor PS, age, or comorbidities. Among patients with non-squamous NSCLC, median received doses of carboplatin and pemetrexed were 1.37 AUC/week and 138.8 mg/m²/week, with RDIs of 86% and 75% (p < 0.01) for patients treated with standard or modified regimens, respectively. Of note, the RDI was 57.9% among patients with ECOG-PS 2. However, patients treated with modified regimens experienced similar toxicities as those treated with standard regimens, despite being older (p < 0.01), with higher PS (p < 0.01) and more comorbid (p = 0.03). Patients treated with modified regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among patients with squamous NSCLC, 90% received modified regimens upfront, with median received doses of carboplatin and paclitaxel of 1.19 AUC/week and 40 mg/m²/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemotherapy plus pembrolizumab in frail patients, the RDI seems to be subtherapeutic, especially in those with squamous histology. Dedicated trials are needed to implement combination strategies in this population.