Journal of Chemotherapy最新文献

Immune checkpoint inhibitors (ICIs) are linked to severe biliary disorders (BDs). Using FAERS data (Q1 2015-Q1 2025), we identified 4,405 BD cases via standardized MedDRA queries (144 preferred terms). ICIs were significantly associated with BDs (overall ROR 3.37, 95% CI 3.28-3.47). Anti‑PD‑1/PD‑L1 monotherapy showed higher risk than anti‑CTLA‑4 (ROR 3.19-4.19 vs 2.57), while combination therapy displayed extreme risks for bile duct necrosis (ROR 530.58) and immune‑mediated cholangitis (ROR 550.54). Fatal outcomes occurred in 19.9% (N=875) and were more common in males, patients aged >65 years, and those weighing <50 kg. Median time‑to‑onset was shortest for anti‑CTLA‑4 (44.8 days, IQR 14-65); fatal cases had earlier onset than nonfatal ones (67.6 vs 114.3 days, P<0.0001). These findings highlight the strong association between ICI therapy and severe biliary injury, supporting the need for early biliary monitoring, particularly in high‑risk patients.

This meta-analysis assessed the latest clinical efficacy and safety of adjuvant chemotherapy (ACT) after concurrent chemoradiotherapy (CCRT) compared to CCRT alone for locally advanced cervical cancer. Studies were pooled via random effects model. Overall survival (OS; risk of death from any cause) and progression-free survival (PFS; risk of disease progression) were primary endpoints. Secondary outcomes included disease-free survival (DFS; absence of recurrence), local failure rate, distant metastasis rate (DMR), and toxicities. A total of 22 studies (n = 7466) were included. CCRT + ACT was associated with significant improvement in OS, PFS, and DMR compared to CCRT alone. Subgroup analyses of RCTs, studies with >3 ACT cycles, and with a follow-up of 5 years indicated no statistical difference in OS and PFS between two groups, suggesting that the clinical advantage of ACT may be limited, particularly given emerging immunotherapies. Moreover, ACT was associated with a higher rate of hematologic and gastrointestinal toxicities.

Alpelisib, a selective phosphatidylinositol-3-kinase alpha (PI3Kα) inhibitor, improves outcomes in hormone receptor-positive (HR+), HER2-negative, PIK3CA-mutated advanced breast cancer, but rare serious toxicities such as pneumonitis may occur. We report a 79-year-old non-smoking woman with ER-positive/HER2-negative breast cancer who initially underwent breast-conserving surgery and adjuvant anastrozole in December 2023. Following local recurrence in October 2024, she received mastectomy and ribociclib-fulvestrant. Disease progression with nodal and osseous metastases was detected in April 2025. Liquid biopsy revealed a PIK3CA H1047R mutation, and alpelisib 150 mg daily plus fulvestrant was initiated in May 2025. After two months, she developed acute dyspnea and hypoxemia without fever. Imaging showed bilateral peripheral ground-glass opacities outside prior radiation fields, and infectious work-up was negative. Bronchoalveolar lavage supported drug-induced pneumonitis. Alpelisib was discontinued, and high-dose corticosteroids led to complete clinical and radiological resolution. This case highlights early-onset alpelisib-induced pneumonitis at a reduced dose and underscores the importance of early recognition and prompt management.

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor-A (VEGF-A), a key mediator of tumor angiogenesis. Among VEGF-A splice variants, VEGF-A_xxxa has proangiogenic activity, whereas VEGF-A_xxxb exerts anti-angiogenic effects. Recent methodological advances have enabled accurate quantitative assessment of the plasma VEGF-A_xxxa, defined as the proportion of VEGF-A_xxxa relative to total VEGF-A. In this study, we evaluated the predictive potential of the VEGF-A_xxxa ratio for bevacizumab efficacy in patients with non-squamous non-small cell lung cancer treated with carboplatin and paclitaxel with or without bevacizumab. A higher VEGF-A_xxxa ratio (≥0.45) was associated with significantly longer progression-free survival and overall survival in the bevacizumab-treated group, with statistically significant treatment interactions. These results suggest that the plasma VEGF-A_xxxa ratio may serve as a minimally invasive biomarker with potential utility for predicting clinical benefit from bevacizumab.

Esophageal cancer has remained a therapeutic challenge despite the advancements in targeted therapy and immunotherapy. This study investigated the mechanism by which neoadjuvant pembrolizumab combined with carboplatin and varying dosages of albumin-bound paclitaxel (ABP) regulates immune microenvironment in esophageal cancer. In vivo, a homograft mouse model was constructed. Both combined treatment groups displayed considerably decreased tumor volume (P < 0.001). Furthermore, the combined treatment inhibited tumor progression by downregulating SHC adaptor protein 4 (shc4) expression, and modulating immune cell homeostasis, as evidenced by remarkably reduced T helper Th1/Th2 and Th17/Regulatory T (Treg) ratios (P < 0.05). Cytokine analysis data revealed that levels of neutrophil cytosolic factor 2 (Ncf2) and related factors were higher in the two combined treatment groups than the Model group (P < 0.05). This study demonstrates that neoadjuvant combination therapy inhibits esophageal cancer progression by reshaping the immune landscape.

General practitioners (GPs) play a crucial role in primary care, particularly during the COVID-19 pandemic, collaborating with Infectious Diseases (ID) specialists. After a training period, a selected group of GPs were able to prospectively enroll patients with mild-moderate COVID-19. Clinical features, symptoms and treatment prescribed were collected. The network provided that GPs could call ID specialists through a dedicated phone number/email address asking for treatment strategies advices. In two months period, 13/16 GPs enrolled 208 patients: 92(44%) females, 110(53%) older than 65 years old. The majority of patients, 156(75%), presented to their GP within 5 days from the symptom onset and 147/201(73%) patients were positive for SARS-CoV-2. The ID consultation was requested for 12/147 (8%) patients and no antibiotic prescription was made on the SARS-CoV-2 positive group.

The future goal would be to expand the network in not COVID-19, improving the management of antibiotic therapy for community acquired respiratory infections.

This multicentre real-world study evaluated the efficacy of targeted therapies in Turkish patients with metastatic squamous cell lung carcinoma harbouring driver mutations. Sixty-four patients with alterations such as EGFR, ALK, and ROS1 who received targeted agents were retrospectively analysed. EGFR mutations were most common (67.2%). Among EGFR-TKI-treated patients, median progression-free survival (PFS) and overall survival (OS) were 12.4 and 14.3 months, respectively. Alectinib yielded a median PFS of 18.6 months and OS of 29.8 months in ALK-positive patients, while crizotinib produced a median PFS and OS of 7 months in ROS1-positive patients. The overall response rate was 50% and the disease control rate 84.4%. Although targeted therapies prolonged PFS compared with chemotherapy, this improvement did not translate into a significant OS advantage, likely influenced by retrospective design and treatment crossover. Findings represent real-world outcomes in a molecularly defined subgroup.

Lung transplantation is a well-established treatment for end-stage lung disease. Viral infections represent major infective complications after lung transplantation. Respiratory viruses can increase immune responses and the development of acute rejection. We describe the case of a 60-year-old man, who underwent bilateral lung transplantation in July 2023. He was admitted to our Unit in December 2024 for worsening shortness of breath associated to dry cough. Arterial blood gas analysis on room air showed respiratory failure. RT-PCR panel for respiratory viruses on a specimen obtained from bronchoalveolar lavage fluid came out positive for Coronavirus OC43, while chest CT-scan showed bilateral patchy infiltrates. Based on in vitro activity data, authorized off-label therapy with remdesivir was administered for 5 days Clinical conditions, together with laboratory data and arterial blood gas analysis, improved quickly. In conclusion, viral infections are a major clinical issue after lung transplant, however targeted therapy is not always possible. New treatment options are needed even to prevent complications, such as acute rejection. This clinical case suggests remdesivir could have a role in non-SARS-CoV-2 coronavirus infections.

Breast cancer is the most common malignancy, with approximately ∼20% of cases involving HER2 overexpression. Trastuzumab deruxtecan (T-DXd), an HER2-targeted antibody-drug conjugate, is approved for HER2-high and HER2-low disease. This meta-analysis assessed four randomized controlled trials (DESTINY-Breast02, -03, -04, and -06; 2555 patients) from PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. A random-effects model revealed that T-DXd significantly improved progression-free survival (hazard ratio [HR] = 0.433; 95% confidence interval [CI]: 0.305-0.616; P < 0.001; I² = 90.7%) and overall survival (HR = 0.720; 95% CI: 0.636-0.816; P < 0.001; I² = 0%) versus control regimens, with consistent benefits across HER2 subgroups. However, T-DXd increased the risks of interstitial lung disease (relative risk [RR] = 13.832; P < 0.001), decreased left ventricular ejection fraction (RR = 2.247; P < 0.001), anemia, nausea, vomiting, decreased appetite, and alopecia; neutropenia and diarrhea risks were comparable between groups. These findings highlight T-DXd's survival benefits and toxicity profile warranting monitoring.

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer represents the most prevalent subtype of breast cancer. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, in combination with endocrine therapy (ET), have shown substantial benefits in improving progression-free survival and, for ribociclib, an overall survival advantage. Despite clinical benefits, ribociclib is associated with elevated liver enzymes and severe liver dysfunction. We present a 44-year-old Caucasian woman with HR-positive, HER2-negative metastatic breast cancer who developed drug-induced autoimmune-like hepatitis (DI-ALH) after ribociclib therapy. Initially treated for early-stage disease with surgery, chemotherapy, radiotherapy, and ET, she progressed to metastatic disease and received ribociclib, letrozole, and goserelin, achieving a partial response. Treatment was complicated by grade 3 hepatotoxicity, confirmed as DI-ALH by liver biopsy. Managed with prednisolone and azathioprine, ribociclib was reintroduced at a reduced dose and later escalated to full dose. This case report highlights the importance of a multidisciplinary approach to balance oncologic efficacy with hepatologic safety.