Journal of Chemotherapy最新文献

Trastuzumab emtansine (T-DM1) is a targeted therapy combining trastuzumab and emtansine for human epidermal growth factor receptor 2(HER2)-positive breast cancer, with common side effects including fatigue, nausea, pain, headache, low platelet count, and elevated liver enzymes. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by vascular malformations and telangiectasias in various organs. We present a case of a female patient with advanced breast cancer who developed HHT-like symptoms while on T-DM1 treatment. A 59-year-old woman treated with radiotherapy and T-DM1 every 21 days developed recurring nosebleeds and mucocutaneous and liver telangiectasias indistinguishable from HHT three months after receiving the first dose of T-DM1. Other organ vascular malformations were ruled out through screening protocols. The patient had no previous HHT symptoms or family history. Nasal care measures like lubrication and antifibrinolytics (tranexamic acid) were provided. In addition, propranolol was also prescribed due to its antiangiogenic and antitumoral properties, leading to significantly decreased epistaxis and telangiectasias. Microtubule disruptions caused by T-DM1, along with other angiogenic mechanisms may contribute to the development of telangiectasias resembling HHT. The use of propranolol, an initial approach for HHT, proved to be effective in this case. It is crucial for oncologists and HHT specialists to be aware of this rare adverse event associated with T-DM1 and to implement appropriate management strategies.

Camrelizumab is an immune checkpoint inhibitor clinically used to treat various types of tumours. In this study, the authors provided the first report of a case of an anaphylactic reaction induced by camrelizumab in the treatment of a patient with squamous cell carcinoma of the floor of the mouth. The patient, a 58-year-old man, was diagnosed with advanced squamous cell carcinoma of the floor of the mouth, with cancer infiltration and multiple metastases. He underwent treatment for nine cycles, in which cycles 1-5 he received camrelizumab, albumin-bound paclitaxel, and cisplatin (200 mg of camrelizumab each time, every 3 weeks), with no adverse reactions; in cycle 6, he received albumin-bound paclitaxel and cisplatin, with no adverse reactions; and in cycles 7-9, he received camrelizumab and albumin-bound paclitaxel. However, 30 min after 8th administration of camrelizumab (cycle 9), he suddenly developed sweating, a pale complexion, clamminess and cyanosis of the limbs (percutaneous arterial oxygen saturation [SpO₂] = 82%, blood pressure [BP] = 79/49 mmHg, heart rate [HR] = 83 beats/min [bpm] and respiratory rate [RR) = 12 bpm). The patient underwent intravenous infusion of methylprednisolone (80 mg) combined with dopamine to boost the BP; he regained consciousness 20 min later, and many parts of his skin appeared smooth, with no desquamation and accompanied by itching erythema, especially on the upper limbs. Approximately 2 h after treatment, the patient's skin erythema subsided (vital sign monitoring results: SpO₂ = 100%, BP = 122/84 mmHg, HR = 91 bpm and RR = 17 bpm); the patient did not complain about his obvious discomfort. Despite the rarity of acute anaphylactic reactions among immune-related adverse reactions, great importance should be given to anaphylactic reactions of camrelizumab due to its extensive clinical application.

Sarcopenia is an independent prognostic factor for several solid cancers, including B-cell non-Hodgkin lymphoma (B-NHL). However, previous reports have measured the parameters of loss of skeletal muscle as sarcopenia only once before chemotherapy and have predicted poor outcomes. In this study, changes in body composition were measured in patients who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy for B-NHL using the InBody 720 analyzer throughout the therapy. Twenty-seven patients who achieved complete remission and survived for one year after the last cycle were included in the study. Body composition was evaluated immediately before initiation and fourth cycle, and one month and one year after the last cycle. Throughout the follow-up period, the lean body mass index (LBMI) and appendicular skeletal muscle mass index (ASMI) showed significant transient decreases even one year following the last cycle (p < 0.001, p = 0.002, respectively). Body fat index (BFI) and body fat percentage (BF%) decreased until one month after the last cycle; however, they reached levels higher than the baseline levels, +22.1% and +15.9%, respectively, at 1 year from the last cycle. The loss of skeletal muscle mass did not recover even one year after the last cycle. Interventions in nutritional management are needed to prevent sarcopenia in patients treated with R-CHOP therapy.

We analyzed the efficacy and safety of aminoglycosides in a retrospective study of 415 patients with acute appendicitis and 277 patients with acute cholecystitis. The following variables increased the incidence of postoperative complications, defined as surgical site infection, recurrent intraabdominal infection, non-infectious post-operative complication, or death: age (p = 0.016 and 0.011), kidney disease (p = 0.019 and <0.001), and ASA Score (p < 0.001). The type of antibiotic therapy did not have a statistically significant effect on the incidence of postoperative complications in patients with acute appendicitis and cholecystitis (p = 0.561 and 0.547, respectively). A linear regression model showed a higher complication rate in patients with kidney disease (p = 0.014) and neoplasms (p = 0.013); the type of antibiotic therapy did not have a significant effect on the outcome (p = 0.765). There was no statistically significant difference in the post-treatment levels of creatinine in patients treated with aminoglycosides (gentamicin 3 mg/kg once daily) and in those who received other antibiotics (p = 0.75).

Colorectal cancer (CRC) is the second leading cause of cancer death, and about 10% of all malignancies are CRC. Cancer stem cells are considered main culprits in CRC treatment resistance and disease recurrence. This study explored the effects of tripartite motif containing 24 (TRIM24) and zinc finger protein, X-linked (ZFX) on CRC cell stemness and 5-FU resistance. A 5-FU-resistant cell line (HT29-5-FU) was constructed for functional analysis of CRC 5-FU-resistant cells. qRT-PCR and western blot (WB) were employed to analyze mRNA and protein levels of ZFX in 5-FU resistant cells and sensitive cells. WB was also utilized to analyze the surface markers of stem cells in each group. CCK-8 assay determined the IC₅₀ values of different cell groups treated with 5-FU. The sphere-forming ability of cells in each group was determined using tumor sphere assay. Dual-luciferase reporter gene assay validated binding of ZFX to TRIM24. ZFX was highly expressed in HT29-5-FU cells. Silencing ZFX significantly reduced the 5-FU resistance and IC₅₀ value of HT29-5-FU cells, and the surface markers and cell sphere-forming ability of stem cells were also significantly reduced. The function of HT29 cells was opposite when ZFX was overexpressed. In CRC cells, TRIM24 was an upstream transcription factor of ZFX, and they interacted with each other. TRIM24 activated the expression of ZFX to influence the stemness and 5-FU resistance of cells. The TRIM24/ZFX regulatory axis affected the stemness of CRC cells and their sensitivity to 5-FU, providing potential drug targets for novel therapeutic avenues for CRC.

We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 - 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.

Oncology patients often experience swallowing difficulties, which can compromise adherence to treatment and consequently reduce its effectiveness. Improper handling of these hazardous drugs can lead to the risk of inhalation of particles or other exposures endangering the health of the persons involved such as nurses and pharmacists. The aim of this review is to analyse and update the recommendations for the manipulation of oral antineoplastic drugs in patients with swallowing difficulties. A literature review of articles, websites, guidelines and other documents published up to about the conditions of handling and administration of oral antineoplastic agents in oncology and oncohaematology was carried out. A table of 110 active principles was compiled. The information was grouped according to the name of the drug, instructions for oral and nasogastric tube administration and suggested recommendations. Among the drugs reviewed, 66.4% were suitable for dissolution. Although there is a lot of information in the literature, the nonstop development of new oncological drugs requires continuous updating. Therefore, we have collected the most recent data to provide a consultation tool for healthcare professionals and patients with swallowing difficulties.

New therapies and vaccines changed the management of COVID-19. The aim of this retrospective study was to describe characteristics, in-hospital mortality and its predictors in patients with moderate/severe COVID-19, considering the 4 different pandemic waves and viral variants' prevalence from February 2020 to January 2022. Among 1135 patients included, 873 (77%) had at least one comorbidity, 177 (16%) were immunocompromised. From waves 1 to 4, patients with severe respiratory failure and ICU admission decreased over time (p < 0.001), like the length of in-hospital stay (p < 0.001). Despite a reduction of in-hospital mortality from 19% to 11%, increased risk of death was related to older age and immunocompromising conditions, especially during the 4th wave (HR = 5.07 and HR = 10.86, p < 0.001 respectively) while remdesivir treatment in the 3rd wave (HR = 0.41, p = 0.010) and positive serology (aHR = 0.66, p = 0.027) were protective for survival. These data support the need for tailoring vaccine campaign for future COVID-19 waves.

The area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio was used as an indicator of the clinical efficacy of vancomycin. However, the target AUC/MIC has not been set for methicillin-resistant coagulase-negative staphylococci (MR-CNS), and the effectiveness of vancomycin in strains with high MIC is unknown. Therefore, we aimed to investigate the relationship between the vancomycin MIC and therapeutic efficacy in patients with MR-CNS bacteremia. The primary outcome was the difference in treatment failure rate when the MR-CNS vancomycin MIC was 1 or 2 µg/mL. The treatment failure rate did not significantly differ between the two groups (MIC 1 vs. MIC 2: 27.0% vs. 31.0%; p = 0.779). As a result of multivariate analysis, AUC/MIC_0-24 h ≤230 was extracted as risk factor for treatment failure, suggesting the importance of a sufficient initial loading dose and early blood concentration monitoring to increase AUC/MIC_0-24 h for successful treatment.

Chidamide, a histone deacetylase inhibitor with established anti-tumor properties, requires further investigation regarding its specific impact on lung cancer progression. Our results showed that chidamide treatment significantly inhibited proliferation, migration, and invasion of non-small cell lung cancer (NSCLC) cells while inducing apoptosis. The treatment with chidamide also downregulated methyltransferase 3 (METTL3), the catalytic subunit of the N6-adenosine-methyltransferase complex, in A549 and H1299 cells. Overexpression of METTL3 reversed the inhibitory effects of chidamide on NSCLC cell progression. Furthermore, we found that METTL3 stabilized EPH receptor A7 (EPHA7) expression through an m6A-dependent mechanism. Conversely, overexpression of EPHA7 counteracted the effects of METTL3 silencing or chidamide treatment in both cell lines. In vivo, chidamide treatment reduced EPHA7 protein expression by regulating METTL3, leading to inhibited tumor growth. Collectively, these findings identified the METTL3/EPHA7 axis as a key mediator of chidamide's anti-tumor effects, suggesting chidamide's potential as a novel therapeutic strategy for NSCLC.