-
Scientific Reports May 2024The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with...
The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with digestive tract, and 36 with breast carcinomas (BC) in advanced stages with poor prognostic characteristics. Patients with colorectal, and pancreas adenocarcinoma received oxaliplatin, irinotecan, FUra, FA (Folfirinox), and patients with squamous cell carcinoma of the esophagus had paclitaxel, carboplatin, FUra, FA (TCbF). Patients with BC received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) followed by TCbF or TCbF only, and patients who overexpressed HER2 received TCbF plus trastuzumab and pertuzumab. PN (1000-3000 mg/day iv) preceded each administration of FUra and FA. 47 patients (94%) responded, including 16 (32%) with CR. Median tumor reduction was 93%. Median event-free survival (EFS) was 37.7 months. The 25 patients with tumor shrinkage ≥ 91% had EFS of 52% from 42 months onwards. Unexpected toxicity did not occur. PN enhances potency of chemotherapy regimens comprising FUra and FA.
Topics: Humans; Fluorouracil; Leucovorin; Pyridoxine; Female; Middle Aged; Aged; Male; Antineoplastic Combined Chemotherapy Protocols; Adult; Breast Neoplasms; Neoplasm Staging; Treatment Outcome
PubMed: 38802419
DOI: 10.1038/s41598-024-62860-z -
Cancers May 2024Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free...
Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, = 110; D-RVd, = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 10/L, = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 10/kg BW, = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, = 0.0164; and 16 vs. 14 days, = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT.
PubMed: 38791933
DOI: 10.3390/cancers16101854 -
Medicine May 2024The aim of this study was to evaluate the efficacy and safety of recombinant human endostatin in combination with vinorelbine + cisplatin (NPE) for the treatment of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the efficacy and safety of recombinant human endostatin in combination with vinorelbine + cisplatin (NPE) for the treatment of advanced non-small cell lung cancer (NSCLC).
METHODS
Randomized controlled trials (RCTs) of NPE for advanced NSCLC in PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched using a computerized search of the database from the time of creation to May 2023. Two investigators independently extracted literature information and assessed the quality of the included literature. Meta-analysis was performed using RevMan 5.4.0 software.
RESULTS
A total of 24 RCTs with 2114 patients with advanced NSCLC were finally included. The results of meta-analysis showed that the total effective rate in the group received NPE regimen was significantly higher than those in the group without NPE regimen (RR = 1.70, 95% CI: 1.48-1.95, P < .00001). Meanwhile, the clinical benefit rate in the group received NPE regimen was also significantly higher than those in the group without NPE regimen (RR = 1.22, 95% CI: 1.15-1.29, P < .00001). However, there was no significant difference in the incidence of adverse event rate between the 2 groups (RR = 0.98, 95% CI: 0.76-1.27, P = .88).
CONCLUSIONS
Compared with NP (vinorelbine + cisplatin) regimens for patients with advanced NSCLC, NPE regimens improve the total effective rate and clinical benefit rate of treatment, but there can be no significant difference in adverse effects. Prospective randomized trials are needed to further validate the safety and efficacy of this treatment modality.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Endostatins; Lung Neoplasms; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Vinorelbine; Recombinant Proteins; Randomized Controlled Trials as Topic
PubMed: 38788043
DOI: 10.1097/MD.0000000000038027 -
Translational Breast Cancer Research :... 2024The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific...
BACKGROUND
The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific treatment target, the age of onset is relatively small, and the recurrence rate is relatively fast. The prognosis of breast cancer in different subtypes is the most unsatisfactory, with a 5-year survival rate of less than 15%. We report a typical case of metastatic advanced triple-negative breast cancer who responded well to apatinib mesylate after chemotherapy failure and achieved significant progression-free survival, which is relatively rare in triple-negative breast cancer with limited treatment means.
CASE DESCRIPTION
A 55-year-old female was surgically diagnosed as triple-negative breast cancer on April 17, 2015. After surgery, she had lung metastasis after standard adjuvant chemotherapy and radiotherapy. After receiving the NX regimen (vinorelbine, capecitabine) for 8 cycles, she progressed. Because the patient refused later, she was adjusted to apatinib mesylate, and serious adverse reactions occurred during the treatment process. By adjusting the drug dose, and low-dose apatinib treatment, the lung lesions were close to complete response (CR), reaching a progression-free survival period of 45 months.
CONCLUSIONS
Low-dose apatinib may be a promising anti-tumor drug for triple-negative breast cancer patients, which needs more samples to verify. This case may provide a reference for the treatment selection of triple-negative metastatic breast cancer in the future.
PubMed: 38751676
DOI: 10.21037/tbcr-23-24 -
Translational Breast Cancer Research :... 2023We report a case of metastatic human epidermal growth factor receptor-2 (HER2) positive breast cancer who achieved encouraging clinical benefits across multiple...
BACKGROUND
We report a case of metastatic human epidermal growth factor receptor-2 (HER2) positive breast cancer who achieved encouraging clinical benefits across multiple pyrotinib-based anti-HER2 therapies.
CASE DESCRIPTION
A 33-year-old woman was diagnosed with hormone receptor (HR) positive, HER2-positive breast cancer in June 2018, and did not receive adjuvant radiotherapy, chemotherapy, or anti-HER2 targeted therapy post-breast conserving surgery. By May 2020, she developed recurrence of the left breast mass with metastases in liver, bone and lymph nodes. She then received pyrotinib plus trastuzumab and nab-paclitaxel as first-line therapy. Both the left breast mass and liver metastases showed noticeable improvement, with the disease evaluated as partial response (PR). Despite this promising result, the patient developed brain metastases after first-line treatment. A combination regimen of pyrotinib retention plus inetetamab and vinorelbine were administered as second-line anti-HER2 therapy, and the brain metastases visibly shrunk, leading to PR, with the extracranial lesions remaining stable. Ultimately, due to brain lesions progression, the treatment was transitioned to trastuzumab deruxtecan. We applied next generation sequencing (NGS) to illustrate the efficacy of anti-HER2 therapy and minimal residual disease (MRD) to detect the disease status.
CONCLUSIONS
Pyrotinib is a promising antineoplastic agent for HER2-positive advanced breast cancer patients. Under the guidance of precision medicine, it is encouraged to utilize novel diagnostic and therapeutic methods to manage advanced breast cancer patients.
PubMed: 38751473
DOI: 10.21037/tbcr-23-26 -
Revista de Investigacion Clinica;... 2024Background: Since to the prognosis of lung squamous cell carcinoma is generally poor, there is an urgent need to innovate new prognostic biomarkers and therapeutic...
Background: Since to the prognosis of lung squamous cell carcinoma is generally poor, there is an urgent need to innovate new prognostic biomarkers and therapeutic targets to improve patient outcomes. Objectives: Our goal was to develop a novel multi-gene prognostic model linked to neutrophils for predicting lung squamous cell carcinoma prognosis. Methods: We utilized messenger RNA expression profiles and relevant clinical data of lung squamous cell carcinoma patients from the Cancer Genome Atlas database. Through K-means clustering, least absolute shrinkage and selection operator regression, and univariate/multivariate Cox regression analyses, we identified 12 neutrophil-related genes strongly related to patient survival and constructed a prognostic model. We verified the stability of the model in the Cancer Genome Atlas database and gene expression omnibus validation set, demonstrating the robust predictive performance of the model. Results: Immunoinfiltration analysis revealed remarkably elevated levels of infiltration for natural killer cells resting and monocytes in the high-risk group compared to the low-risk group, while macrophages had considerably lower infiltration in the high risk group. Most immune checkpoint genes, including programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4, exhibited high expression levels in the high risk group. Tumor immune dysfunction and exclusion scores and immunophenoscore results suggested a potential inclination toward immunotherapy in the "RIC" version V2 revised high risk group. Moreover, prediction results from the CellMiner database revealed great correlations between drug sensitivity (e.g., Vinorelbine and PKI-587) and prognostic genes. Conclusion: Overall, our study established a reliable prognostic risk model that possessed significant value in predicting the overall survival of lung squamous cell carcinoma patients and may guide personalized treatment strategies. (Rev Invest Clin. 2024;76(2):116-31).
Topics: Humans; Lung Neoplasms; Neutrophils; Prognosis; Carcinoma, Squamous Cell; Male; Female; Biomarkers, Tumor; Middle Aged; Aged; Gene Expression Regulation, Neoplastic; RNA, Messenger
PubMed: 38740381
DOI: 10.24875/RIC.23000262 -
Cancer Medicine Apr 2024Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic...
BACKGROUND
Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC.
METHODS
This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS.
RESULTS
The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%).
CONCLUSION
Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.
Topics: Humans; Female; Pyridines; Vinorelbine; Middle Aged; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Adult; Retrospective Studies; Aged; Breast Neoplasms; Administration, Oral; Progression-Free Survival
PubMed: 38659376
DOI: 10.1002/cam4.7181 -
BMC Cancer Apr 2024This study aimed to systematically analyze the effect of a serine/threonine kinase (STK11) mutation (STK11) on therapeutic efficacy and prognosis in patients with... (Meta-Analysis)
Meta-Analysis
Effect of the STK11 mutation on therapeutic efficacy and prognosis in patients with non-small cell lung cancer: a comprehensive study based on meta-analyses and bioinformatics analyses.
BACKGROUND
This study aimed to systematically analyze the effect of a serine/threonine kinase (STK11) mutation (STK11) on therapeutic efficacy and prognosis in patients with non-small cell lung cancer (NSCLC).
METHODS
Candidate articles were identified through a search of relevant literature published on or before April 1, 2023, in PubMed, Embase, Cochrane Library, CNKI and Wanfang databases. The extracted and analyzed data included the hazard ratios (HRs) of PFS and OS, the objective response rate (ORR) of immune checkpoint inhibitors (ICIs), and the positive rates of PD-L1 expression. The HR of PFS and OS and the merged ratios were calculated using a meta-analysis. The correlation between STK11 and clinical characteristics was further analyzed in NSCLC datasets from public databases.
RESULTS
Fourteen retrospective studies including 4317 patients with NSCLC of whom 605 had STK11 were included. The meta-analysis revealed that the ORR of ICIs in patients with STK11 was 10.1% (95%CI 0.9-25.2), and the positive rate of PD-L1 expression was 41.1% (95%CI 25.3-57.0). STK11 was associated with poor PFS (HR = 1.49, 95%CI 1.28-1.74) and poor OS (HR = 1.44, 95%CI 1.24-1.67). In the bioinformatics analysis, PFS and OS in patients with STK11 alterations were worse than those in patients without alterations (p < 0.001, p = 0.002). Nutlin-3a, 5-fluorouracil, and vinorelbine may have better sensitivity in patients with STK11 than in those with STK11.
CONCLUSIONS
Patients with STK11-mutant NSCLC had low PD-L1 expression and ORR to ICIs, and their PFS and OS were worse than patients with STK11 after comprehensive treatment. In the future, more reasonable systematic treatments should be explored for this subgroup of patients with STK11-mutant NSCLC.
Topics: Humans; AMP-Activated Protein Kinase Kinases; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutation; Prognosis; Protein Serine-Threonine Kinases; Retrospective Studies
PubMed: 38632512
DOI: 10.1186/s12885-024-12130-y -
Discover Oncology Apr 2024Long non-coding RNAs (LncRNAs) regulating the immune microenvironment of cancer is a hot spot. But little is known about the influence of the immune-related lncRNA...
BACKGROUND
Long non-coding RNAs (LncRNAs) regulating the immune microenvironment of cancer is a hot spot. But little is known about the influence of the immune-related lncRNA (IRlncRs) on the chemotherapeutic responses and prognosis of cervical cancer (CC) patients. The purpose of the study was to identify an immune-related lncRNAs (IRlncRs)-based model for the prospective prediction of clinical outcomes in CC patients.
METHODS
CC patients' relevant data was acquired from The Cancer Genome Atlas (TCGA). Correlation analysis and Cox regression analyses were applied. A risk score formula was formulated. Prognostic factors were combined into a nomogram, while sensitivity for chemotherapy drugs was analyzed using the OncoPredict algorithm.
RESULTS
Eight optimal IRlncRs(ATP2A1-AS1, LINC01943, AL158166.1, LINC00963, AC009065.8, LIPE-AS1, AC105277.1, AC098613.1.) were incorporated in the IRlncRs model. The overall survival (OS) of the high-risk group of the model was inferior to those in the low-risk group. Further analysis demonstrated this eight-IRlncRs model as a useful prognostic marker. The Nomogram had a concordance index of survival prediction of 0.763(95% CI 0.746-0.780) and more robust predictive accuracy. Furthermore, patients in the low-risk group were found to be more sensitive to chemotherapy, including Paclitaxel, Rapamycin, Epirubicin, Vincristine, Docetaxel and Vinorelbine.
CONCLUSIONS
An eight-IRlncRs-based prediction model was identified that has the potential to be an important tool to predict chemotherapeutic responses and prognosis for CC patients.
PubMed: 38615287
DOI: 10.1007/s12672-024-00979-1 -
Animal Models and Experimental Medicine Apr 2024Breast cancer is the most common cancer in women, and in advanced stages, it often metastasizes to the brain. However, research on the biological mechanisms of breast...
BACKGROUND
Breast cancer is the most common cancer in women, and in advanced stages, it often metastasizes to the brain. However, research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited.
METHODS
Differential gene expression analysis (DEGs) for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox. Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal. Thus, expression levels, variations, associations with HER2, biological processes, and pathways involving SULF1 could be analyzed using UALCAN, cBioPortal, GEPIA2, and LinkedOmics databases. Moreover, the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP.
RESULTS
High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2. In the metastatic breast cancer population, SULF1 ranked top among the 16 DEGs with the highest mutation rate, reaching 11%, primarily due to amplification. KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the 'ECM-receptor interaction' gene set and negatively enriched in the 'Ribosome' gene set. Currently, docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high.
CONCLUSIONS
This study, through bioinformatics analysis, unveiled SULF1 as a potential target for treating breast cancer brain metastasis (BM).
PubMed: 38590118
DOI: 10.1002/ame2.12406