Chemotherapy最新文献

Introduction: Duodenal squamous cell carcinoma is an exceedingly rare occurrence among gastrointestinal malignancies, and its diagnosis and treatment are not well understood.

Case presentation: In this report, we present a case of duodenal squamous cell carcinoma with liver and adrenal metastasis. The patient was treated with gemcitabine and S-1, achieving a progression-free survival of 7 months and an overall survival of 9 months. Additionally, we review the features and treatment approaches reported in previous cases of primary duodenal carcinoma.

Conclusion: Clearly, further case reports, such as ours, can contribute to a deeper understanding that is essential for characterizing this entity and establishing management guidelines.

Introduction: Nocardia spp. is an opportunistic pathogen capable of causing localized and disseminated infections in immunocompromised hosts. It is critical for serious infections to have an early and accurate identification of this pathogen in order to enable timely and focused combination antimicrobial treatment.

Case presentation: We describe the case of an 87-year-old patient previously treated for myasthenia gravis with corticosteroids and azathioprine. Patient was admitted at the emergency department with clinical signs of sepsis with cellulitis of right hand associated with injury acquired after gardening and trimming roses and did not respond to empirical antimicrobial treatment. Computerized tomography revealed pulmonary infiltrates with inflammatory etiology. Nocardia cyriacigeorgica was cultivated from blood culture, skin swab, abscess aspirate, and endotracheal aspirate and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA sequencing, and whole genome sequencing (WGS). Susceptibility testing was performed with E-test (bioMerieux, Marcy-l'Étoile, France), and corresponding resistance genes were detected by WGS. Resistance to amoxicillin-clavulanate, azithromycin, ciprofloxacin, and vancomycin was detected by both methods. Despite all interventions and the patient receiving antimicrobial treatment including imipenem-cilastatin, amikacin, and trimethoprim-sulfamethoxazole, the course and outcome of infection were unfavorable.

Conclusion: We would like to emphasize the need to consider the possibility of disseminated Nocardia infection in immunocompromised patients, especially in patients receiving long-term corticosteroid treatment with skin infections and/or cavitary lung lesions, especially if these do not improve with standard antimicrobial treatment. Precise species identity provides a critical guide for physicians in the choice of targeted treatment. Thanks to MALDI-TOF MS, Nocardia spp. identification is now available in routine lab work. WGS is still inevitable for the identification of uncommon and novel species due to the high sequence similarities between closely related species and the genetic diversity of that genus.

Introduction: High-dose methotrexate (MTX) is used to treat pediatric acute lymphoblastic leukemia (ALL). The drug has a low therapeutic index and a highly interindividual variability in systemic exposure. These characteristics necessitate dose adjustments and therapeutic drug monitoring protocols, while population pharmacokinetic (POP/PK) models may enable more precise drug dosing. Therefore, we assessed the performance of external POP/PK models in ALL children receiving high-dose MTX.

Methods: We retrospectively harvested clinical and laboratory data from ALL children during their first two cycles of chemotherapy. A POP/PK model was elaborated using the Monolix suite 2024R1. External models were selected from PUBMED based on strict inclusion/exclusion criteria, and their fit to the actual data was assessed by calculating bias (percentage prediction error [PE%]) and precision (percentage root mean squared error [RMSE%]).

Results: Thirty-seven ALL children participated in the study (18 males, median age 5.1 years, range 1.7-15.2 years), and six external POP/PK models were chosen. Except for one model (median PE% value, -97.45%), all models exhibited acceptable bias (median PE% values, -4.17%-2.67%), despite none of them demonstrating good precision (median RMSE% values, 89.19%-120.40%).

Conclusion: External models should be accurately evaluated before they are implemented in clinical practice, even when patients share very similar characteristics.

Introduction: This study aims to evaluate the efficacy and safety of cryoablation combined with pembrolizumab treatment versus cryoablation alone in patients with advanced non-small cell lung cancer (NSCLC).

Methods: This retrospective study was conducted from February 2018 to October 2021. A total of 90 patients with NSCLC (AJCC stage IIIB/IV) were included, with 36 patients receiving cryoablation combined with pembrolizumab (group A) and 54 patients receiving cryoablation alone (group B). The primary outcome measures included objective response rate (ORR), overall survival (OS), and progression-free survival (PFS), immune responses, and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses.

Results: No treatment-related deaths were observed. Group A demonstrated a higher ORR (75.0% vs. 61.1%), longer median OS (28.1 months vs. 24.2 months), and longer median PFS (12.8 months vs. 8.4 months) compared to Group B. Additionally, group A showed significant increases in CD3+, CD4+, and CD8+ T cells, and elevated levels of interleukin-2, interleukin-6, TNF-β, and interferon-γ. The multivariate analysis showed the combination of cryoablation and pembrolizumab was an independent prognostic factor for OS and PFS.

Conclusions: Cryoablation combined with pembrolizumab significantly improves clinical outcomes in advanced NSCLC patients compared to cryoablation alone, highlighting the potential of this combination therapy in enhancing antitumor immunity and prolonging survival.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of chemotherapy. Low carnitine levels might negatively affect the development of CIPN. However, little is known of the course of carnitine levels during and directly after chemotherapy administration. Intervention studies using carnitine to prevent CIPN were contradictory, possibly due to different timing and route of carnitine supplementation. Better understanding of carnitine courses might improve future studies. This study aimed to investigate whether oxaliplatin-based chemotherapy administration affects blood and urinary levels of carnitine. We hypothesized that oxaliplatin increases renal excretion of carnitine, thereby causing a carnitine deficiency, which might contribute to the development of CIPN.

Methods: Ten patients, starting their first cycle of oxaliplatin-based chemotherapy, were enrolled in this observational pilot study. Blood and urinary samples were taken before, during and after infusion of oxaliplatin. Primary endpoints were changes in plasma and urinary concentrations of free carnitine and carnitine esters during administration of oxaliplatin-based chemotherapy.

Results: This study showed a significant decrease of both free carnitine and carnitine esters in plasma 2 h after the start of infusion of oxaliplatin-based chemotherapy. Moreover, a non-significant increase in urine carnitine concentration was seen during the chemotherapy infusion.

Conclusion: The altered plasma and urinary concentrations of carnitine support our hypothesis that oxaliplatin causes increased renal excretion of carnitine, thereby lowering blood-carnitine levels and increasing urinary carnitine levels. With continued loss of carnitine over several chemotherapy cycles, this may result in the development of carnitine deficiency, which could contribute to the development of CIPN. These preliminary results provide a basis for hypothesis generation; larger longitudinal studies are required to confirm these findings and to determine the clinical relevance.

Introduction: Epiploic appendagitis is an uncommon cause of acute abdominal pain, often mimicking surgical emergencies. This case highlights the diagnostic process for epiploic appendagitis in a breast cancer patient receiving abemaciclib, a CDK4/6 (cyclin-dependent kinase) inhibitor, and discusses potential associations with targeted therapies.

Case presentation: We present a case of a 48-year-old female on adjuvant abemaciclib for stage IIIA breast cancer who developed acute left iliac fossa pain. Clinical assessment, laboratory investigations, transvaginal ultrasound, and subsequent computed tomography (CT) imaging of the abdomen and pelvis were performed to establish the diagnosis. CT imaging revealed a characteristic ovoid fat-density lesion with surrounding inflammation adjacent to the sigmoid colon, consistent with epiploic appendagitis. Other differential diagnoses, including ovarian pathology and diverticulitis, were excluded. The patient was managed conservatively with analgesia, and the abemaciclib was temporarily discontinued and restarted at a lower dose, leading to symptom resolution. This case underscores the importance of considering epiploic appendagitis in the differential diagnosis of acute abdominal pain, particularly in patients on targeted therapies like abemaciclib, which are known to have gastrointestinal side effects. Timely and accurate diagnosis via imaging avoided unnecessary surgical intervention.

Conclusion: This case is the first of its kind to propose a novel association between the use of targeted therapies such as abemaciclib and the development of inflammatory conditions such as epiploic appendagitis. It emphasises the crucial role of clinical suspicion and appropriate imaging in establishing this rare diagnosis. Further research is warranted to explore potential links between CDK4/6 inhibitors and the development of epiploic appendagitis.

Introduction: This study investigates the efficacy of fucoidan combination with antibiotics, against single-species biofilms and mixed-species, individual planktonic, and coculture planktonic conditions of Methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii by time-kill curve analysis.

Materials and methods: Fucoidan, a sulfated polysaccharide, was purchased from Sigma-Aldrich, USA. Clinical isolates of MRSA and A. baumannii from diabetic foot ulcers (DFUs) were used, and single-species biofilms and mixed-species biofilms were developed to assess susceptibility to the treatments using MIC, MBC, minimum biofilm inhibitory concentration, minimum biofilm eradication concentration, and time-kill kinetics assays. Cytotoxicity was assessed using MTT assays on human skin fibroblast cells (HSF-PI 16).

Results: The study determined the geometric mean MIC and MBC values for gentamicin, imipenem, and fucoidan in MRSA and A. baumannii cultures, both individually and in co-cultures. The MIC and MBC values were significantly lower under co-culture conditions, indicating enhanced antimicrobial efficacy. Synergy between fucoidan, gentamicin, and imipenem was confirmed through time-kill assays, which showed complete inhibition of bacterial growth and effective biofilm eradication, particularly in mixed-species biofilms. Fucoidan demonstrated low cytotoxicity at optimal concentrations, highlighting their potential as a therapeutic strategy against biofilm-associated infections in DFUs.

Conclusion: The study concludes that fucoidan, in combination with gentamicin and imipenem, effectively disrupts mixed-species biofilms of MRSA and A. baumannii, suggesting fucoidan-based therapies could improve outcomes for DFU patients, warranting further clinical investigation.

Introduction: Our study aimed to identify relevant features associated with the reprisal of antineoplastic treatment in patients with solid cancers after unplanned admittance to the intensive care unit (ICU) and to assess 60th-month survival in patients with solid neoplasms admitted to the ICU.

Methods: This single-centre retrospective study of critically ill patients with active cancers was performed over a 13-year period (2005-2018). Patients' characteristics, overall survival, and antineoplastic treatment reprisal were extracted from digital medical files and compared.

Results: 134 patients were included in the study. Solid neoplasms were mostly localised to the head and neck (n = 53) followed by lung cancers (n = 29). Sepsis was the leading cause of ICU admission (62.1%) with 41/82 patients presenting with septic shock. Antineoplastic treatments were resumed in 40 patients. An age ≤60 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1 were found to be predictors for treatment reprisal, with odd ratios of, respectively, 2.83 (95% CI, 1.15-6.99) and 5.45 (95% CI, 2.01-14.82); area under the ROC curve of 72% (95% CI, 63-81%). Survival after the immediate discharge from the ICU was 101/134 (75%) and the 60-month survival rate was 29% and significantly higher in the treatment-reprisal group.

Conclusions: Age and ECOG PS were found to be predictors for treatment reprisal in patients with solid neoplasms admitted to the ICU. The latter benefits from better long-term survival.

Introduction: Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) therapy is indicated as first-line or neoadjuvant chemotherapy (NAC) for patients with advanced or metastatic urothelial carcinoma (UC). However, no studies reported ddMVAC therapy with pegfilgrastim (3.6 mg) in Japanese patients. We investigated the safety and efficacy of ddMVAC therapy with pegfilgrastim in patients with advanced or metastatic UC.

Methods: A total of 43 patients received ddMVAC therapy with pegfilgrastim (3.6 mg) from February 2021 to December 2023. Among them, 25 and 18 patients received this regimen as first-line chemotherapy and NAC, respectively. We assessed toxicity and efficacy using Common Terminology Criteria for Adverse Events version 4.0 and Response Evaluation Criteria in Solid Tumors version 1.1, respectively.

Results: The median number of ddMVAC therapy cycles was 3 (range: 1-5), with a total of 131 cycles. Cisplatin at the full dose without reduction was administered to 24 (56%) patients. Grade ≥3 hematologic toxicity occurred in 15 (35%) patients. Among them, anemia, neutropenia, thrombocytopenia, and febrile neutropenia were 13.9%, 9.3%, 11.7%, and 7.0%, respectively. Regarding non-hematologic toxicity, grade 3 appetite loss was observed in 2 (5%) patients. Complete response was observed in 7 (16%) patients and partial response in 26 patients (60%), yielding an objective response rate of 76%. Pathologic complete response (pCR; ypT0pN0) was observed in 3 (16.7%) patients and downstaging occurred in 13 (72.2%) patients. The median progression-free survival and overall survival of first-line treatment with ddMVAC were 18.6 months and not reached, respectively.

Conclusion: The ddMVAC with pegfilgrastim (3.6 mg) reduced injection-related patient burden, caused fewer grade ≥3 adverse events, and demonstrated similar efficacy when compared to the original ddMVAC regimen that used granulocyte colony-stimulating factor for 7 consecutive days.

Introduction: Pembrolizumab has been approved for the first-line treatment of patients with advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. However, the results of several clinical trials are not entirely consistent, and the dominant population of first-line immunotherapy for advanced GC/GEJ still needs to be precisely determined.

Purpose: The aim of this meta-analysis was to assess the efficacy and safety of pembrolizumab in the treatment of advanced GC/GEJ.

Methods: We conducted computerized searches across multiple databases, including PubMed, Cochrane Library, Web of Science, and Embase. We established the inclusion criteria to comprise randomized clinical trials examining the efficacy of pembrolizumab in late-stage GC/GCJ cancer. We conducted a meta-analysis of outcome measures using STATA 14.0 software.

Results: A total of six studies involving 1,448 cases were included in this analysis. The results of the meta-analysis indicate that, when compared to chemotherapy, patients in the pembrolizumab group experienced a significant reduction in the risk of mortality in terms of overall survival (OS) (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.65-0.79, p < 0.01). In terms of progression-free survival (PFS), pembrolizumab was associated with a similar PFS as compared to chemotherapy (HR = 0.88, 95% CI: 0.73-1.07, p = 0.206). Subgroup analyses based on PD-L1 expression levels indicated a significantly longer PFS with pembrolizumab in subgroups of patients with PD-L1 CPS ≥10 but not in those with PD-L1 CPS ≥1 and PD-L1 CPS ≥5. Subgroup analyses based on distinct geographical regions revealed a comparable effect of PFS in patients residing in Asia or the USA Subgroup analysis based on tumor sites consistently demonstrated a similar effect of PFS in patients with EC/GEJ tumors and GC patients.

Conclusion: Our findings demonstrated that pembrolizumab led to a significant extension in OS and objective response rate, along with a favorable tolerability profile compared to chemotherapy. Furthermore, the observed survival benefits were particularly pronounced in subgroup patients with a CPS of ≥10. Given the potential limitations inherent in our study, it is imperative to underscore the necessity for further large-scale RCTs to corroborate our results.