Journal of Chemotherapy最新文献

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.

A two-compartmental mathematical pharmacokinetic model with first-order elimination of patients receiving CAPD of 4 exchanges for 6 h with 2 L of dialysate used in each cycle was developed to predict daptomycin disposition in 120 h of therapy. The pharmacodynamic target was plasma AUC/MIC equal to or greater than 666. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. Administering intraperitoneal 300 mg daily for 1 exchange daily regimen would be sufficient to treat peritonitis with S. aureus infection with MICs of 0.25 mg/L in patients undergoing CAPD. A higher dosage may be required for infections with a higher minimum inhibitory concentration. Pharmacodynamic targets and MICs significantly contributed to daptomycin doses in this setting. Clinical validation of our recommendations is recommended.

This study investigated the Mpox outbreak that occurred in a health cluster of three hospitals in Riyadh, Saudi Arabia, involving 97 patients diagnosed between May and December 2023. Among them, 48% were Saudi nationals, 94% were men, and 73% were under 35 years old. While sexual activity was a potential transmission mode, only 38% of patients reported it. All patients were presented with skin lesions and common symptoms like fever, headaches, and itching, with two being HIV positive. Genotyping revealed all samples were from subclade IIb (West Africa clade). Unlike previous outbreaks, rashes and systemic symptoms emerged simultaneously without a prodromal phase. Stringent infection control measures kept healthcare workers safe, although underreporting of sexual behavior may limit the study's findings. This highlights the need for Mpox consideration in young individuals with skin lesions.

Ganciclovir, a guanine analogue, is used intravenously (IV) first-line for the prophylaxis and treatment of cytomegalovirus (CMV) infection in solid organ transplant recipients. The pharmacokinetics (PK) of ganciclovir are highly variable, with myelosuppression occurring at high concentrations. Ganciclovir is primarily renally excreted as the parent compound, and clearance is significantly reduced in renal impairment. Acute kidney injury (AKI) is a common post-operative complication of cardiac transplantation, reducing the clearance of ganciclovir. In the intensive care unit (ICU), AKI is often managed by kidney replacement therapy (KRT). One form of KRT, prolonged intermittent kidney replacement therapy (PIKRT) is increasingly used for cost and flexibility advantages. Ganciclovir dosing recommendations are available for varying degrees of renal impairment and KRT, except for PIKRT. In this case of cardiac transplantation, complicated by anuric AKI, a ganciclovir dose of 2.0-2.5 mg/kg of adjusted body weight given after each PIKRT session was demonstrated to achieve PK targets.

Better in vitro models are needed to identify active drugs to treat pancreatic adenocarcinoma (PAC) patients. We used 3D hanging drop cultures to produce spheroids from five PAC cell lines and tested nine FDA-approved drugs in clinical use. All PAC cell lines in 2D culture were sensitive to three drugs (gemcitabine, docetaxel and nab-paclitaxel), however most PAC (4/5) 3D spheroids acquired profound chemoresistance even at 10 µM. In contrast, spheroids retained sensitivity to the investigational drug triptolide, which induced apoptosis. The acquired chemoresistance was also transiently retained when cells were placed back into 2D culture and six genes potentially associated with chemoresistance were identified by microarray and confirmed using quantitative RT-PCR. We demonstrate the additive effect of gemcitabine and erlotinib, from the 12 different combinations of nine drugs tested. This comprehensive study shows spheroids as a useful multicellular model of PAC for drug screening and elucidating the mechanism of chemoresistance.

Advanced non-small cell lung cancer (NSCLC) remains a significant clinical challenge, particularly in patients who exhibit stable disease (SD) following first-line chemotherapy combined with immunotherapy. This study aims to evaluate the efficacy and safety of Anlotinib, a novel multitarget tyrosine kinase inhibitor, as maintenance therapy in this patient cohort. This retrospective, single-center study enrolled patients with advanced NSCLC who showed SD after receiving a combination of first-line chemo-immunotherapy for 4 cycles, then add anlotinib to subsequent standard maintenance therapy, continuing treatment until disease progression or the occurrence of intolerable toxic side effects. The primary endpoint was progression-free survival (P FS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety profile. A total of 52 patients were enrolled, the median P FS and OS was 5.0m and 10.0m, respectively. The ORR and DCR was 28.85% and 67.31%. subgroup analysis indicated that its efficacy correlate with certain Adverse Effects (AEs, such as hypertension, proteinuria, and hand-foot syndrome). Further mechanistic analysis suggests that this regimen may likely reduce immune suppression by depleting Tregs, thereby further activating the immune system to exert synergistic anti-tumor effects. Besides promising efficacy, the toxicity can be tolerated. Anlotinib demonstrates promising efficacy as a maintenance therapy in patients with advanced NSCLC who have achieved SD following first-line chemotherapy combined with immunotherapy. The manageable safety profile and the observed extension in P FS and OS suggest that Anlotinib could be a valuable therapeutic option for this challenging patient population. Further large-scale randomized controlled trials are warranted to confirm these findings and to optimize patient selection and management strategies.

We aimed to evaluate the relationship between the cumulative area under the concentration-time curve (AUC) for the first and second day of vancomycin (VCM) administration and acute kidney injury (AKI). The primary outcome was the cumulative incidence of AKI. Patients were divided into three groups based on the measured AUC_0-48 h at the first therapeutic drug monitoring (TDM) (800 to less than 1000 µg·h/mL, Low-AUC group; 1000 to less than 1200 µg·h/mL, Moderate-AUC group; ≥1200 µg·h/mL, High-AUC group). Among 180 enrolled patients, 29 (16.1%) developed AKI. In the multivariate Cox proportional hazard analysis, the Moderate- (hazard ratio [HR]: 5.7, 95% confidence interval [CI]: 2.24-14.44) and High- (HR: 11.0, 95% CI: 3.88-31.39) AUC groups were associated with a higher incidence of AKI compared to the Low-AUC group. The accumulation toxicity of VCM was observed, and the cumulative AUC_0-48 h was associated with the development of AKI.

Background: Mal, T cell differentiation protein 2 (MAL2) has emerged as a potential regulator in the progression of bladder cancer (BCa). Therapeutic resistance to sunitinib poses a significant challenge in BCa treatment. This study investigates the role of MAL2 in modulating BCa malignant development and its influence on sunitinib sensitivity.

Methods: The mRNA levels of MAL2 and E2F transcription factor 1 (E2F1) were analyzed by quantitative real-time polymerase chain reaction, whereas their protein expression was detected by western blotting. Cell proliferation was analyzed by 5-Ethynyl-2'-deoxyuridine assay. Cell apoptotic rate was quantified by flow cytometry. Cell migration and invasion were analyzed through transwell assays. The sensitivity of BCa cells to sunitinib was analyzed by cell counting kit-8 assay. Fe²⁺ and malondialdehyde levels were analyzed through colorimetric assays. Reactive oxygen species levels were analyzed through fluorometric assay. The molecular interactions between E2F1 and MAL2 were explored using chromatin immunoprecipitation and dual-luciferase reporter assays. The in vitro findings regarding the effects of E2F1 and MAL2 on the malignant progression of BCa cells were further corroborated in vivo using xenograft mouse models.

Results: The expression of MAL2 was elevated in both BCa tissues and cells. Silencing MAL2 expression led to a suppression of BCa cell proliferation, migration, and invasion, while simultaneously enhancing cell apoptosis and ferroptosis, and increasing sensitivity to sunitinib. E2F1 was identified as a transcriptional activator of MAL2 in T24 and J82 BCa cells, and its overexpression fostered the malignant progression of BCa cells and reduced their responsiveness to sunitinib. Additionally, the adverse effects of E2F1 silencing on BCa cell behavior were mitigated by the overexpression of MAL2 in vitro and in vivo.

Conclusion: E2F1-induced transcriptional activation of MAL2 promoted the progression of BCa and inhibited sunitinib sensitivity, offering a potential novel therapeutic approach for BCa patients.