Journal of Chemotherapy最新文献

BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are approved in the U.S. to be given in combination or as single agents to treat patients with BRAF V600E/K-positive solid and histiocytic neoplasms. During postmarketing safety surveillance, we identified cases of photosensitivity with BRAFi (dabrafenib, encorafenib) and MEKi (trametinib, binimetinib) and evaluated this finding further using data from the Food and Drug Administration's Adverse Event Reporting System, the literature, and the drug manufacturers. We identified 72 cases of photosensitivity with BRAFi/MEKi with a median time to onset of 60 days. Cases described erythema, pruritis, blistering, pain, and swelling. Based on a temporal relationship; positive dechallenge after BRAFi/MEKi discontinuation, interruption, or dose reduction; and positive rechallenge with drug re-exposure, findings from our case series suggest a causal association between BRAFi/MEKi and photosensitivity, and this is further supported by pre-market, non-clinical testing results.

This research aimed to assess the effectiveness of daratumumab in the treatment of relapsed and refractory multiple myeloma (RRMM) within a real - world setting. We conducted a retrospective analysis of the clinical features and treatment outcomes of patients diagnosed with RRMM at the Union Hospital of Fujian Medical University from 2018 to 2024. The study cohort consisted of 62 patients, with a median age of 62 years. 80.6% of patients received one line therapy before administration of daratumumab. The median follow - up duration was 16.1 (1.9 - 69.6) months, and the median number of daratumumab treatment cycles was 7.5 (1 - 72) courses. Among the 56 evaluable cases, the overall response rate (ORR) was 89.3%, which included 11 cases (19.6%) attaining a stringent complete response (sCR) and 13 cases (23.2%) achieving a complete response (CR). The median progression free survival (PFS) of the entire cohort was 25.2 months. The 1 - year and 3 - year PFS rates were 75.2% and 25.4% respectively. The median overall survival (OS) was 42.7 months. The 1 - year and 3 - year OS rates were 84.2% and 62.8% respectively. Multivariate analysis indicated that poor performance status was independent unfavorable prognostic factors for PFS and OS. In conclusions, an early daratumumab - based treatment regimen has demonstrated promising therapeutic potential for treating RRMM and warrants further validation and exploration in future clinical practice.

Background: Paclitaxel is a widely used chemotherapeutic agent for the treatment of breast cancer. While peripheral neuropathy is a well-recognized dose-limiting toxicity of paclitaxel, cranial nerve involvement remains exceptionally rare. We report a case of unilateral facial nerve palsy in a breast cancer patient receiving standard-dose paclitaxel therapy, highlighting the diagnostic challenges in distinguishing drug-induced neurotoxicity from other aetiologies.

Case report: A 43-year-old woman with metastatic breast cancer developed left facial nerve paralysis after 12 months of weekly paclitaxel treatment (80 mg/m²). Contrast-enhanced cranial Magnetic Resonance Imaging (MRI) demonstrated bilateral cranial nerve VII enhancement, creating diagnostic uncertainty between leptomeningeal metastasis, paclitaxel-induced neuritis, and idiopathic Bell's palsy. Paclitaxel was discontinued, and corticosteroid therapy was initiated. Clinical and radiological improvement at follow-up strongly supported a drug-related aetiology.

Conclusion: This case illustrates the diagnostic complexity of facial nerve palsy in cancer patients receiving neurotoxic chemotherapy. The overlapping clinical and radiological features between drug-induced cranial neurotoxicity, leptomeningeal disease, and idiopathic causes present significant diagnostic challenges. Clinicians should maintain a high degree of suspicion for rare chemotherapy-related cranial neuropathies while pursuing comprehensive differential diagnosis, including infectious aetiologies and metastatic disease.

This retrospective study evaluated the clinical efficacy of camrelizumab combined with transarterial chemoembolization (TACE) in 120 hepatocellular carcinoma (HCC) patients with liver cirrhosis. Based on the intervention received, patients were categorized into an observation group (OG) (n = 60, underwent camrelizumab combined with TACE interventional therapy) and a control group (CG) (n = 60, underwent camrelizumab monotherapy). The OG showed significantly higher objective response (66.67% vs. 46.67%) and disease control rates (91.67% vs. 80.00%), improved immune function (elevated CD3⁺, CD4⁺, CD4⁺/CD8⁺), better liver function (reduced TB and ALT), and reduced tumor markers (AFP, CEA) compared to the CG. One-year follow-up revealed prolonged overall survival rate and progression-free survival, along with better quality-of-life scores in the OG. These findings suggest that camrelizumab combined with TACE demonstrates definitive short-term efficacy, improved immune and liver function, better survival outcomes, and favorable safety in HCC patients with liver cirrhosis, supporting its clinical value.

This study is the first to investigate the therapeutic potential of a mono/combination treatment with the selective phase III BCR::ABL1 tyrosine kinase inhibitor (TKI) asciminib (ABL001) and the c-MET inhibitor tivantinib (ARQ197) in hematopoietic stem cells (HSCs) and leukaemia stem cells (LSCs) in terms of cytotoxicity, apoptosis, target gene expression profiles, and bioinformatics in vitro. In silico studies were also performed for various tivantinib and asciminib derivatives. Asciminib and tivantinib exhibited significant antileukaemic effects, with tivantinib showing the strongest apoptotic impact in LSCs and asciminib in HSCs. Although their combination exhibited an additive effect on LSCs, enabling dose reduction and potentially minimizing side effects; the treatment succeeded in promoting apoptosis as effectively as tivatinib monotherapy. Gene expression analysis showed increased pro-apoptotic and tumour suppressor markers, whereas decreased oncogenes' expressions following mono/combined treatment in LSCs. Molecular docking showed that a new analogue of tivantinib (compound-1) and CHEMBL5274046 are promising c-MET and ABL1 inhibitors, respectively. The findings highlight the antileukaemic potential of initially tivantinib and asciminib in LSCs. Despite an additive effect, combination therapy allowed dose reduction, giving rise to a potential decrease in side effects. Targeting c-MET, alone or in combination with BCR::ABL1 inhibition, presents a compelling strategy for eradicating LSCs, which underpin resistance and relapse in CML therapy - thus marking a crucial advancement in the pursuit of more effective treatment paradigms. In silico studies indicated that various tivantinib and asciminib analogues could also have potential therapeutic effects as c-MET and ABL1 inhibitors for future anti-leukaemia research.

This study explored the efficacy of fruquintinib monotherapy versus fruquintinib combined with immune checkpoint inhibitors in the treatment of advanced proficient mismatch repair/microsatellite stable-type colorectal cancer. We retrospectively collected data from patients (n=75) diagnosed with advanced colorectal cancer at our hospital from January 2020 to December 2022 who chose to receive fruquintinib monotherapy or combine it with immune checkpoint inhibitors for treatment. The primary endpoint was progression-free survival (PFS) and overall survival (OS). As of July 1, 2023, the median PFS for the fruquintinib monotherapy group and combination therapy was 3.9 months and 7.9 months , respectively (P = 0.142). The median OS in the monotherapy group and combination therapy was 10.3 months and 10.0 months, respectively (P = 0.942). However, as compared with the monotherapy group, the combination therapy group showed a trend for a prolonged duration of PFS, and it may have good application potential.

Acute myeloid leukemia (AML) is a heterogeneous malignancy specified by clonal proliferation of hematopoietic stem cells. This study identifies novel therapeutics for AML by integrating differential gene expression (DEG) and survival analyses. Publicly available GEO microarray datasets were analyzed, including data from 615 AML patients and 22 healthy controls. Multivariate Cox regression identified hazardous genes impacting survival. Protein-protein interaction networks using CytoScape revealed hub genes such as CCT5, ZBTB16, APP, and PTPN6. Functional enrichment revealed key AML-related pathways, such as PI3K/Akt and NF-kappaB signaling. Drug repurposing using the LINCS L1000CDS2 database highlighted potential therapeutics, including 16-Hydroxytriptolide and Tryptosthin AG-1478, with roles in reversing hazardous gene expression patterns. Additional candidates such as Vemurafenib, Parthenolide and Wortmannin, demonstrated promise as targeted agents. These findings underscore the potential of integrating bioinformatics and drug discovery to identify precision medicine in AML. Further studies are warranted to validate these targets and explore their clinical utility.

Immune checkpoint inhibitors (ICIs), have emerged to the forefront of management for various advanced cancers, such as melanoma, lung cancer and renal cell carcinoma. Immune checkpoints such as CTLA-4 and PD-1 serve to inhibit T cell activation and signaling; therefore through blockade of these pathways, ICIs promote anti-tumour immune activation. However, as a result of T cell disinhibition, ICIs have been reported to cause immune related adverse events (irAEs) affecting numerous organ systems. One of the most serious and potentially life-threatening irAE is inflammatory myositis. Myositis, which generally presents with progressive proximal muscle weakness and elevated serum creatine kinase (CK), has been reported in <1% of patients who have received ICI therapy. A rare cause of elevated CK is adrenal insufficiency, which has been reported in up to 6% of ICI users. Here we report a case of ICI-related hypophysitis related myopathy that was initially misdiagnosed as ICI-associated inflammatory myositis. This case illustrates the importance of considering a wide differential when assessing hyperCKemia in the setting of ICI use.

Clear cell sarcoma is an ultra-rare chemoresistant subtype of soft tissue sarcoma. This retrospective analysis aimed to clarify the efficacy of palliative chemotherapy in CCS by assessing response rates, progression-free survival (PFS), and overall survival (OS) at a referral center. A retrospective analysis of palliative treatment was conducted on patients with CCS treated at the sarcoma unit from 1997 to 2023. Treatment responses were assessed using RECIST criteria, and the Kaplan-Meier method was used to calculate PFS and OS. The analysis covered 23 CCS chemotherapy-treated patients with 11 (47.8%) men. The median age at the palliative treatment start was 32 years (range 18-59). The median follow-up was 8.2 months. Four patients were referred to our centre for M1 disease, and 6 received perioperative chemotherapy and progressed during follow-up. In the first line, 14 patients received anthracycline-based chemotherapy (60.9%), five were treated with ifosfamide (HD-IFO), and four received other regimens. One patient (4.3%) achieved partial response (PR), and 12 patients (52.2%) achieved stable disease (SD) as the best response. Median PFS in 1 line was 2.79 months (95% CI: 2.04-8.38), and 1.76 months (95% CI: 0.72-6.97) in the second line. The median OS from first-line palliative chemotherapy was 8.2 months (95% CI: 6.2-14), and the second-line palliative chemotherapy mOS was 4.6 months (95% CI: 3.9-NA). Perioperatively anthracycline-pretreated worsened patients' median PFS in the M1 setting. Poor responses to conventional chemotherapy were observed in CCS, indicating a need for further clinical trials in this indication.

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.