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Anticancer Research Apr 2022This study compared the results of nivolumab treatment in patients with pulmonary adenocarcinomas based upon previous chemotherapeutic regimens.
AIM
This study compared the results of nivolumab treatment in patients with pulmonary adenocarcinomas based upon previous chemotherapeutic regimens.
PATIENTS AND METHODS
The data source for this retrospective study was the Czech VILP registry of patients with nivolumab-treated adenocarcinomas in second and higher lines of treatment. In relation to objective response rate, progression-free interval, and overall survival, three comparisons of patient were made: A: Those treated in first line with cisplatin and pemetrexed versus carboplatin with paclitaxel or vinorelbine; B: treatment with cisplatin and pemetrexed versus carboplatin with paclitaxel/vinorelbine and bevacizumab; and C: treatment in previous lines with pemetrexed (first-line cisplatin and pemetrexed plus those treated in second line with pemetrexed) versus treatment with taxane (first-line carboplatin and paclitaxel only plus those treated with second-line docetaxel).
RESULTS
We observed no differences in objective response rate or progression-free survival between patients treated with the stated chemotherapeutic regimens. We observed a trend towards better overall survival for patients treated with carboplatin plus taxanes or vinorelbine with/without bevacizumab.
CONCLUSION
From our overall survival data, a chemotherapeutic regimen of carboplatin plus taxanes or vinorelbine with/without bevacizumab might be a better partner for immunotherapy than a cisplatin and pemetrexed-based one.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Nivolumab; Retrospective Studies
PubMed: 35347019
DOI: 10.21873/anticanres.15677 -
Journal of Clinical Oncology : Official... Dec 2022JCO The randomized, open-label, phase II EVAN study investigated the efficacy (disease-free survival [DFS] and 5-year overall survival [OS]) and safety of erlotinib... (Randomized Controlled Trial)
Randomized Controlled Trial
Updated Overall Survival and Exploratory Analysis From Randomized, Phase II EVAN Study of Erlotinib Versus Vinorelbine Plus Cisplatin Adjuvant Therapy in Stage IIIA Epidermal Growth Factor Receptor+ Non-Small-Cell Lung Cancer.
JCO The randomized, open-label, phase II EVAN study investigated the efficacy (disease-free survival [DFS] and 5-year overall survival [OS]) and safety of erlotinib versus vinorelbine/cisplatin as adjuvant chemotherapy after complete resection (R0) for stage III epidermal growth factor receptor () mutation+ non-small-cell lung cancer. We describe the updated results at the 43-month follow-up. In EVAN, patients were randomly assigned (1:1) to erlotinib (n = 51) or vinorelbine/cisplatin (n = 51). The median follow-up was 54.8 and 63.9 months in the erlotinib and chemotherapy arms, respectively. With erlotinib, the respective 5-year DFS by Kaplan-Meier analysis was 48.2% (95% CI, 29.4 to 64.7) and 46.2% (95% CI, 27.6 to 62.9) in the intention-to-treat and per-protocol populations. The median OS was 84.2 months with erlotinib versus 61.1 months with chemotherapy (hazard ratio, 0.318; 95% CI, 0.151 to 0.670). The 5-year survival rates were 84.8% and 51.1% with erlotinib and chemotherapy, respectively. In whole-exome sequencing analysis, frequent genes with variants co-occurring at baseline were , , , , and . With erlotinib, a single-nucleotide polymorphism mutation in was associated with significantly worse DFS ( = .01). To our knowledge, this study is the first to demonstrate clinically meaningful OS improvement with adjuvant erlotinib compared with chemotherapy in R0 stage III EGFR+ non-small-cell lung cancer.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Vinorelbine; Cisplatin; Lung Neoplasms; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Staging; ErbB Receptors; Disease-Free Survival; Mutation; Axonemal Dyneins
PubMed: 36027483
DOI: 10.1200/JCO.22.00428 -
Oncology Letters Mar 2020gene encodes the hepatoma upregulated protein (HURP), a microtubule associated protein regulating mitotic spindle dynamics, which promotes chromosomal congression and...
gene encodes the hepatoma upregulated protein (HURP), a microtubule associated protein regulating mitotic spindle dynamics, which promotes chromosomal congression and alignment during mitosis, with a potential role in tumorigenesis. In the present study, mRNA expression was investigated by reverse transcription-quantitative PCR in oropharyngeal squamous cell carcinoma (OPSCC). Primary OPSCC tumors from 107 patients and 48 adjacent normal tissues, as well as 12 respiratory tract cancer cell lines (9 head and neck squamous cell carcinoma, 2 lung cancer and 1 normal bronchial) were utilised in the present study. mRNA expression levels of were higher in malignant OPSCC tissues compared with in normal mucosa (P<1×10) and significantly associated with sex and smoking status (P<0.0001). Vinorelbine toxicity at half-maximal inhibitory concentration (IC) was measured in the 11 cancer cell lines using an MTT assay. Sensitivity to vinorelbine was significantly correlated with HURP expression (r=0.636; P=0.035). The data indicated that overexpression is frequent in OPSCC tissues and associated with smoking. The correlation between mRNA expression and vinorelbine response suggests that HURP is a potential modulator of vinorelbine response; therefore, it should be explored for its possible predictive value for the efficiency of vinorelbine treatment in this type of cancer.
PubMed: 32194751
DOI: 10.3892/ol.2020.11339 -
Archiv Der Pharmazie Sep 2020The bisindole moiety, as a versatile pharmacophore, is one of the widespread heterocycles in naturally occurring and synthetic bioactive compounds. The bisindole... (Review)
Review
The bisindole moiety, as a versatile pharmacophore, is one of the widespread heterocycles in naturally occurring and synthetic bioactive compounds. The bisindole alkaloids derived from natural sources possess structural and mechanistic diversity, and they were found to be generally more active than monoindole alkaloids against various cancer cell lines. Moreover, some bisindole alkaloids such as the tubulin inhibitors, vinorelbine and vinblastine, have already been approved for cancer therapy, suggesting that bisindole alkaloids are a significant source of anticancer agents and lead hits. Bisindole hybrids have the potential to overcome drug resistance, enhance efficiency, and reduce severe side effects. The bisindole-lactam hybrid midostaurin has already been approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia who are FLT3 mutation-positive, highlighting the importance of bisindole hybrids in the development of novel anticancer agents. In this review, we present a brief account of the bisindole alkaloids derived from nature and of synthetic hybrids with potential anticancer activity developed in the recent 10 years.
Topics: Adult; Animals; Antineoplastic Agents, Phytogenic; Drug Development; Drug Resistance, Neoplasm; Humans; Indole Alkaloids; Neoplasms; Structure-Activity Relationship
PubMed: 32468606
DOI: 10.1002/ardp.202000092 -
Current Cancer Drug Targets 2024This study aimed to observe the efficacy and safety of inetetamab and pyrotinib in combination with vinorelbine in second-line therapy and beyond in HER2-positive...
The Efficacy and Safety of Inetetamab and Pyrotinib in Combination with Vinorelbine for Second-line Therapy and Beyond in HER2-positive Metastatic Breast Cancer: A Single-institution Clinical Experience.
BACKGROUND AND OBJECTIVES
This study aimed to observe the efficacy and safety of inetetamab and pyrotinib in combination with vinorelbine in second-line therapy and beyond in HER2-positive metastatic breast cancer (MBC).
METHODS
Patients with HER2-positive MBC admitted to our hospital from January 2016 to December 2021 were selected. For patients who could not receive antibody‒drug conjugates (ADCs) during second-line (2-line) or third-line and beyond (≥ 3-line) anti-HER2 therapy, inetetamab + pyrotinib + vinorelbine was used for treatment until unacceptable adverse events occurred or the disease progressed, as evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 every 2 cycles. The progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and adverse reactions were recorded. Multivariate Cox regression analysis was performed to explore the prognostic factors influencing the curative effect.
RESULTS
Overall, 52 patients were included; 13 patients received 2-line treatment, and 39 patients received ≥ 3-line treatment. The median PFS (mPFS) for all patients treated with inetetamab + pyrotinib + vinorelbine was 7 months. The mPFS of the 2-line subgroup was significantly better than that of the ≥ 3-line subgroup (17 vs. 5 months, P = 0.001). The mPFS of the subgroups that received trastuzumab (H) or trastuzumab and pertuzumab (HP) only was significantly better than that of the H or HP and tyrosine kinase inhibitor (TKI) subgroups (8 vs. 5 months, P = 0.030). The mPFS of the HER2 resistance subgroup was better than that of the HER2 refractoriness subgroup (14 vs. 7 months, P = 0.025). Cox regression analysis showed that the treatment line (2-line more so than ≥ 3-line) was an independent prognostic factor for PFS. In addition, the ORR and CBR of 2-line patients were significantly higher than those of ≥ 3-line patients (69.2% vs. 30.8% and 92.3% vs. 64.1%, respectively). The most common hematological toxicities were leukopenia and neutropenia, and the most common nonhematological toxicity was diarrhea.
CONCLUSION
Inetetamab and pyrotinib in combination with vinorelbine have good efficacy in ≥ 2-line treatment of HER2-positive MBC with controllable toxicity, and the combination is a new treatment option, especially for patients who cannot use ADCs in 2-line treatment.
Topics: Humans; Vinorelbine; Female; Breast Neoplasms; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Receptor, ErbB-2; Aged; Adult; Acrylamides; Progression-Free Survival; Retrospective Studies; Aminoquinolines
PubMed: 37916639
DOI: 10.2174/0115680096248592231016065117 -
Leukemia Research Sep 2019Salvage regimens in relapsed/refractory Hodgkin's lymphoma (HL) differ in their efficacy and toxicity profiles. Gemcitabine (G), vinorelbine (V) and liposomal...
BACKGROUND
Salvage regimens in relapsed/refractory Hodgkin's lymphoma (HL) differ in their efficacy and toxicity profiles. Gemcitabine (G), vinorelbine (V) and liposomal doxorubicin (GVDoxil) is one regimen with high response rates but has high toxicity and cost. We devised a regimen of GVDex by substituting the more expensive liposomal doxorubicin with the cheaper high-dose dexamethasone (Dex).
PATIENTS AND METHODS
We analyzed the data of 48 adult and paediatric patients of relapsed/refractory HL who received GVDex as salvage therapy. GVDex was delivered as outpatient once in 3 weeks (Q3 weekly) (G 1000 mg/m IV over 30 min on D1, 8; V 25 mgm IV fast infusion on D1, 8; Dex40 mg PO D1-4) for 2-3 cycles. We present the overall response rate, toxicity, progression-free (PFS) and overall survival (OS) from the time of start of GVDex.
RESULTS
Forty-eight patients [median age: 24 years (5-63)] received GVDex [(median cycles:3(1-6)] in this period. Median time from diagnosis to the first relapse was 18.9 (2-119) months. Overall response rate [ORR = complete (CR)+partial (PR)] was 63%. Eleven (23%) patients developed febrile neutropenia. After a median follow-up of 20 months, the Kaplan-Meier estimates of patients alive and progression-free at 24 months were 60% and 49%, respectively.
CONCLUSIONS
The response rates with GVDex were comparable to those reported with GVDoxil when used as a first-line salvage regimen in relapsed/refractory HL. It was an effective regimen even in patients who failed 2 lines of therapy for HL.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Deoxycytidine; Dexamethasone; Female; Hodgkin Disease; Humans; Male; Middle Aged; Recurrence; Retreatment; Salvage Therapy; Treatment Outcome; Vinorelbine; Young Adult; Gemcitabine
PubMed: 31325732
DOI: 10.1016/j.leukres.2019.106188 -
Medicine May 2023The extensive and intricate relationships between circadian rhythm and cancer have been reported in numerous studies. However, in breast cancer (BC), the potential role...
The extensive and intricate relationships between circadian rhythm and cancer have been reported in numerous studies. However, in breast cancer (BC), the potential role of circadian clock-related genes (CCRGs) in prognosis prediction has not been fully clarified. The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. A CCRGs-based risk signature was established by differential expression analysis, univariate, Lasso and multivariate Cox regression analyses. we conducted a gene set enrichment analysis (GSEA) between groups. A nomogram integrating independent clinical factors and risk score was generated and evaluated by calibration curves and decision curve analysis (DCA). Differentially expression analysis revealed 80 differentially expressed CCRGs, and 27 of them were significantly associated with the overall survival (OS) of BC. BC can be classified into 4 molecular subtypes with significant differences in prognosis based on the 27 CCRGs. Three prognostic CCRGs, including desmocollin 1 (DSC1), LEF1, and protocadherin 9 (PCDH9), were identified to be independent risk factors of BC prognosis and were used to construct a risk score model. BC patients were divided into high- and low-risk groups, and there were significant differences in prognosis between the 2 groups both in the training and validation cohorts. It was found that patients in different groups of race, status, or T stage had significant levels of risk score. Furthermore, patients of different risk levels exhibit varying degrees of sensitivity to vinorelbine, lapatinib, metformin, and vinblastine. GSEA showed that in the high-risk group, immune response-related activities were dramatically repressed whereas cilium-related processes were significantly stimulated. Cox regression analysis demonstrated that age, N stage, radiotherapy and the risk score were independent prognostic risk factors of BC, and a nomogram was established based on these variables. The nomogram exerted a favorable concordance index (0.798) as well as calibration performance, which strongly supports the clinical application of the nomogram. Our study indicated the disruption of the expression of CCRGs in BC and built a favorable prognostic risk model based on 3 independent prognostic CCRGs. These genes may be applied as candidate molecular targets for the diagnosis and therapy of BC.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Nomograms; Vinblastine; Vinorelbine
PubMed: 37144994
DOI: 10.1097/MD.0000000000033718 -
Cancer Cell International Jun 2022Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and... (Review)
Review
Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and drug therapy, along with others, which not only put a tremendous economic effect on patients but also develop drug resistance in patients with time. A significant number of cancer cases can be prevented/treated by implementing evidence-based preventive strategies. Plant-based drugs have evolved as promising preventive chemo options both in developing and developed nations. The secondary plant metabolites such as alkaloids have proven efficacy and acceptability for cancer treatment. Apropos, this review deals with a spectrum of promising alkaloids such as colchicine, vinblastine, vincristine, vindesine, vinorelbine, and vincamine within different domains of comprehensive information on these molecules such as their medical applications (contemporary/traditional), mechanism of antitumor action, and potential scale-up biotechnological studies on an in-vitro scale. The comprehensive information provided in the review will be a valuable resource to develop an effective, affordable, and cost effective cancer management program using these alkaloids.
PubMed: 35655306
DOI: 10.1186/s12935-022-02624-9 -
Frontiers in Cell and Developmental... 2021Esophageal cancer is the eighth most common malignancy and the sixth leading cause of cancer-related deaths worldwide. Chemotherapy based on platinum drugs,... (Review)
Review
Esophageal cancer is the eighth most common malignancy and the sixth leading cause of cancer-related deaths worldwide. Chemotherapy based on platinum drugs, 5-fluorouracil, adriamycin, paclitaxel, gemcitabine, and vinorelbine, as well as targeted treatment and immunotherapy with immune checkpoint inhibitors improved the prognosis in a portion of patients with advanced esophageal cancer. Unfortunately, a number of esophageal cancer patients develop drug resistance, resulting in poor outcomes. Multiple mechanisms contributing to drug resistance of esophageal cancer have been reported. Notably, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), have been identified to play crucial roles in modulating esophageal cancer drug resistance. In the present review, we highlight the underlying mechanisms how miRNAs, lncRNAs, and circRNAs impact the drug resistance of esophageal cancer. Several miRNAs, lncRNAs, and circRNAs may have potential clinical implications as novel biomarkers and therapeutic targets for esophageal cancer.
PubMed: 34881242
DOI: 10.3389/fcell.2021.764313 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Jul 2021To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin...
OBJECTIVE
To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG and to evaluate the therapeutic efficacy of the codelivery nano-micelles in breast cancer treatment.
METHODS
T+V-CS micelles were prepared by ultrasonic-dialysis method, and the physicochemical characterization were evaluated using multiple technological means. The anti-tumor efficacy of T+V-CS micelles was evaluated by MTT assay and cell cycle arrest analysis. Evaluation of the therapeutic effect of T+V-CS micelles was carried out on xenograft 4T1 murine breast cancer bearing BALB/c mice model.
RESULTS
T+V-CS micelles displayed a nearly spherical shape when observed through transmission electron microscope. The particle size and polydispersity indexes (PDI) of T+V-CS micelles was (155.5±4.5) nm and 0.170±0.003 respectively, while the Zeta potential was (-23.0±0.9) mV. Meanwhile, T+V-CS micelles demonstrated high encapsulation efficiency of (81.87±2.56)% for THP and (87.54±2.82)% for VRL and a high overall drug loading efficiency of (10.20±1.20)%. and studies of the therapeutic efficacy of breast cancer showed that T+V-CS micelles had synergistic anti-tumor effect and induced increased G /M cell cycle arrest in 4T1 cells, which could significantly inhibit tumor growth and prolong survival compared with the therapeutic efficacy of micelles loaded with a single kind of drug or free drug solutions.
CONCLUSION
The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer.
Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Carriers; Female; Humans; Mice; Mice, Inbred BALB C; Micelles; Polyethylene Glycols; Vinorelbine
PubMed: 34323039
DOI: 10.12182/20210760105