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Breast Cancer (Dove Medical Press) 2021Eribulin mesylate, a synthetic derivative of the anti-mitotic agent halichondrin B, has a unique tubulin-based mechanism of action that is distinct from other... (Review)
Review
Eribulin mesylate, a synthetic derivative of the anti-mitotic agent halichondrin B, has a unique tubulin-based mechanism of action that is distinct from other anti-microtubule agents including taxanes and vinca alkaloids. Consistent with this unique activity, eribulin has shown clinical efficacy in patients with metastatic breast cancer (MBC) that progressed following prior taxane and anthracycline therapy. The evidence presented in this review indicates that eribulin represents a treatment option for patients with HER2-negative metastatic breast cancer. Improved survival outcomes and better tolerability compared with vinorelbine supported the first approval of eribulin in China in 2019; eribulin was approved for women with locally advanced/metastatic HER2-negative breast cancer after treatment failure with at least two chemotherapy regimens, including an anthracycline and a taxane. Eribulin has also shown promising efficacy in patients with HER2-positive advanced breast cancer when used in combination with trastuzumab or pertuzumab, and subgroup analyses from the Phase III clinical trials support the continued evaluation of eribulin in patients with triple-negative disease. The unique non-mitotic effects of eribulin, including vascular remodeling, coupled with its clinical efficacy and safety profile, may permit the broader use of this agent in patients with MBC.
PubMed: 33658845
DOI: 10.2147/BCTT.S231298 -
Surgery Open Science Dec 2023The purpose of this study was to compare the efficacy and safety of utidelone plus capecitabine for advanced first-line versus second-line or above therapy in metastatic...
BACKGROUND
The purpose of this study was to compare the efficacy and safety of utidelone plus capecitabine for advanced first-line versus second-line or above therapy in metastatic breast cancer patients who had previously received anthracycline and taxane. At the same time, we compared the efficacy of utidelone plus capecitabine and vinorelbine plus cisplatin in advanced first-line treatment of metastatic breast cancer.
PATIENTS AND METHODS
A retrospective cohort of 11 patients with metastatic breast cancer previously treated with anthracycline and taxane (including neoadjuvant and adjuvant therapies) for advanced first-line with utidelone plus capecitabine, 32 patients treated with second-line or above, and 60 patients with vinorelbine plus cisplatin between October 2011 and August 2022 was collected. The first and second groups were treated with utidelone plus capecitabine, and the third group was treated with vinorelbine plus cisplatin. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), objective response rate (ORR), and treatment safety.
RESULTS
By 03/31/2023, median PFS reached 11.70 months (95 % CI 0.093-0.141) in utidelone plus capecitabine group in the advanced first-line therapy, compared to 5.60 months (95 % CI 0.025-0.079) in the second-line or above therapy [HR 0.42, (95 % CI 0.226-0.787), P = 0.0077]. In utidelone plus capecitabine, the median OS was not reached in the advanced first-line therapy, with a mean overall survival of 23.16 months (95 % CI 0.198-0.265); whereas the median OS in the second-line or above therapy was 19.50 months (95 % CI 0.083-0.307), with a mean overall survival of 16.89 months (95 % CI 0.136-0.202) [HR 0.26, (95 % CI 0.098-0.678), P = 0.0495]. The ORR for advanced first-line therapy was 27.27 % (95%CI 0.060, 0.610) compared with 15.63 % (95%CI 0.053, 0.328) for second-line or above. In advanced first-line therapy, utidelone plus capecitabine was superior to vinorelbine plus cisplatin with a median PFS of 6.12 months (95 % CI 0.051-0.072) [HR 0.49, (95 % CI 0.286-0.839), P = 0.0291]. Compared with utidelone plus capecitabine, the median OS in vinorelbine plus cisplatin advanced first-line therapy group was 35.37 months (95 % CI 0.258-0.449), and the mean overall survival was 40.79 months (95 % CI 0.315-0.501) [HR 0.54, (95 % CI 0.188-1.568), P = 0.2587]. The ORR for vinorelbine plus cisplatin was 18.33 % (95 % CI 0.095, 0.304). The most common adverse events in our study were neurological toxicity, hand-foot syndrome, hematological toxicity, gastrointestinal toxicity, and hepatic and renal function abnormalities. There were no deaths due to adverse effects during the utidelone plus capecitabine treatment period.
CONCLUSIONS
In MBC, advanced first-line therapy with utidelone plus capecitabine resulted in more favorable PFS, OS, and ORR than second-line or above therapy. In advanced first-line therapy, utidelone plus capecitabine had superior PFS, and ORR compared with vinorelbine plus cisplatin. This study concludes that utidelone plus capecitabine is a more valuable chemotherapy option in advanced first-line MBC.
PubMed: 38026829
DOI: 10.1016/j.sopen.2023.10.008 -
Molecular Oncology Feb 2024The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor...
NOTCH1 and CREBBP co-mutations negatively affect the benefit of adjuvant therapy in completely resected EGFR-mutated NSCLC: translational research of phase III IMPACT study.
The phase III IMPACT study (UMIN000044738) compared adjuvant gefitinib with cisplatin plus vinorelbine (cis/vin) in completely resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Although the primary endpoint of disease-free survival (DFS) was not met, we searched for molecular predictors of adjuvant gefitinib efficacy. Of 234 patients enrolled in the IMPACT study, 202 patients were analyzed for 409 cancer-related gene mutations and tumor mutation burden using resected lung cancer specimens. Frequent somatic mutations included tumor protein p53 (TP53; 58.4%), CUB and Sushi multiple domains 3 (CSMD3; 11.8%), and NOTCH1 (9.9%). Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival (OS) in the gefitinib group and cAMP response element binding protein (CREBBP) co-mutation for DFS and OS in the cis/vin group. In patients with NOTCH1 co-mutations, gefitinib group had a shorter OS than cis/vin group (Hazard ratio 5.49, 95% CI 1.07-28.00), with a significant interaction (P for interaction = 0.039). In patients with CREBBP co-mutations, the gefitinib group had a longer DFS than the cis/vin group, with a significant interaction (P for interaction = 0.058). In completely resected EGFR-mutated NSCLC, NOTCH1 and CREBBP mutations might predict poor outcome in patients treated with gefitinib and cis/vin, respectively.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Gefitinib; Lung Neoplasms; Cyclic AMP Response Element-Binding Protein; Translational Research, Biomedical; ErbB Receptors; Cisplatin; Vinorelbine; Mutation; Protein Kinase Inhibitors; Receptor, Notch1; CREB-Binding Protein
PubMed: 37864465
DOI: 10.1002/1878-0261.13542 -
Cell Death & Disease Jul 2020The use of aspirin has been associated with reduced breast cancer risk, but it is litter known if aspirin overcomes chemoresistance in triple-negative breast cancer...
The use of aspirin has been associated with reduced breast cancer risk, but it is litter known if aspirin overcomes chemoresistance in triple-negative breast cancer (TNBC). Herein, we demonstrated that changes in the expression of Yes-associated protein (YAP) and β-catenin might be a promising predictive biomarker for neoadjuvant chemotherapy sensitivity in TNBC patients. Inhibition of YAP or β-catenin enhanced the cytotoxicity of the anti-microtubule agents docetaxel and vinorelbine against drug-resistant TNBC cells as well as the sensitivity of these cells to the agents in vitro and in vivo. Interestingly, aspirin not only significantly inhibited the growth of TNBC cells, but also attenuated YAP and β-catenin expression by upregulating the E3 ubiquitin ligase β-TrCP to abolished docetaxel and vinorelbine resistance. The combination of aspirin and docetaxel or vinorelbine remarkably inhibited the growth of drug-resistant TNBC cells in vitro and in vivo. Moreover, TNBC patients with high YAP and/or β-catenin expression had a higher risk of relapse or mortality than patients with low YAP and/or β-catenin expression. Collectively, our study discovered a novel role of aspirin based on its anticancer effect, and put forward some possible mechanisms of chemoresistance in TNBC. The combined use of aspirin and anti-microtubule drugs presented several promising therapeutic approaches for TNBC treatment.
Topics: Animals; Aspirin; Cell Cycle Proteins; Disease Models, Animal; Drug Resistance, Neoplasm; Female; Humans; Mice; Mice, Nude; Transcription Factors; Triple Negative Breast Neoplasms; beta Catenin
PubMed: 32661222
DOI: 10.1038/s41419-020-2719-2 -
Strahlentherapie Und Onkologie : Organ... Jan 2022Treatment of muscle-invasive bladder cancer (MIBC) remains challenging, especially for elderly and/or comorbid patients. Patients who are unfit for or refuse surgery...
PURPOSE
Treatment of muscle-invasive bladder cancer (MIBC) remains challenging, especially for elderly and/or comorbid patients. Patients who are unfit for or refuse surgery should receive bladder-preserving multimodality treatment (BPMT), consisting of transurethral resection of the bladder tumor (TURB) followed by combined chemoradiotherapy (CRT). We aimed to investigate the effectiveness of vinorelbine, a chemotherapeutic agent not routinely used for MIBC, in patients referred to CRT who are unfit for standard chemotherapy and would thus rely solely on radiotherapy (RT).
METHODS
We retrospectively analyzed 52 consecutive patients with MIBC who received standard CRT with cisplatin (n = 14), CRT with vinorelbine (n = 26), or RT alone (n = 12). Primary endpoints were median overall survival (OS) and median cancer-specific survival (CSS). Secondary endpoints were median local control (LC), median distant control (DC), and OS, CSS, LC, and DC after 1, 2, and 3 years, respectively.
RESULTS
Median OS and CSS were significantly higher for patients who received vinorelbine as compared to RT alone (OS 8 vs. 22 months, p = 0.003; CSS 11 months vs. not reached, p = 0.001). Median LC and DC did not differ significantly between groups. Vinorelbine was well tolerated with no reported side effects >grade II.
CONCLUSION
Our results suggest that CRT with vinorelbine is well tolerated and superior to RT alone in terms of OS and CSS. Therefore, this treatment regime might constitute a new treatment option for patients with MIBC who are unfit for or refuse surgery or standard chemotherapy. This study encourages a randomized controlled trial to compare this new regime to current standard therapies.
Topics: Aged; Cisplatin; Humans; Muscles; Neoplasm Invasiveness; Retrospective Studies; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms; Vinorelbine
PubMed: 34414475
DOI: 10.1007/s00066-021-01837-7 -
BioRxiv : the Preprint Server For... Jun 2023Type I interferons (IFNs) increase the excitability of dorsal root ganglion (DRG) neurons via activation of MNK-eIF4E translation signaling to promote pain sensitization...
Type I interferons (IFNs) increase the excitability of dorsal root ganglion (DRG) neurons via activation of MNK-eIF4E translation signaling to promote pain sensitization in mice. Activation of STING signaling is a key component of type I IFN induction. Manipulation of STING signaling is an active area of investigation in cancer and other therapeutic areas. Vinorelbine is a chemotherapeutic that activates STING and has been shown to cause pain and neuropathy in oncology clinical trials in patients. There are conflicting reports on whether STING signaling promotes or inhibits pain in mice. We hypothesized that vinorelbine would cause a neuropathic pain-like state in mice via STING and signaling pathways in DRG neurons associated with type I IFN induction. Vinorelbine (10 mg/kg, i.v.) induced tactile allodynia and grimacing in WT male and female mice and increased p-IRF3 and type I IFN protein in peripheral nerves. In support of our hypothesis, vinorelbine-mediated pain was absent in male and female Sting mice. Vinorelbine also failed to induce IRF3 and type I IFN signaling in these mice. Since type I IFNs engage translational control via MNK1-eIF4E in DRG nociceptors, we assessed vinorelbine-mediated p-eIF4E changes. Vinorelbine increased p-eIF4E in DRG in WT animals but not in Sting or (MNK1 KO) mice. Consistent with these biochemical findings, vinorelbine had an attenuated pro-nociceptive effect in male and female MNK1 KO mice. Our findings support the conclusion that activation of STING signaling in the peripheral nervous system causes a neuropathic pain-like state that is mediated by type I IFN signaling to DRG nociceptors.
PubMed: 37333411
DOI: 10.1101/2023.06.03.543579 -
British Journal of Cancer Dec 2019The continuum of anti-HER2 agents is a standard treatment of HER2 + metastatic breast cancer (MBC). This study evaluated the efficacy of lapatinib plus vinorelbine... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised Phase 2 study of lapatinib and vinorelbine vs vinorelbine in patients with HER2 + metastatic breast cancer after lapatinib and trastuzumab treatment (KCSG BR11-16).
BACKGROUND
The continuum of anti-HER2 agents is a standard treatment of HER2 + metastatic breast cancer (MBC). This study evaluated the efficacy of lapatinib plus vinorelbine in patients progressed on both trastuzumab and lapatinib treatments.
METHODS
A total of 149 patients were randomly assigned to lapatinib with vinorelbine (LV) (n = 75; lapatinib, 1000 mg daily; vinorelbine 20 mg/m D1, D8 q3w) or vinorelbine (V) (n = 74; 30 mg/m D1, D8 q3w). The primary endpoint was progression-free survival (PFS) rate at 18 weeks.
RESULTS
The median number of previous anti-HER2 therapies was 2 (range 2-5). There was no significant difference in PFS rate at 18 weeks between LV and V arms (45.9% vs 38.9%, p = 0.40). ORR was 19.7% in LV arm, and 16.9% in V arm (p = 0.88). PFS and OS did not differ between two arms (LV vs V; median PFS, 16 vs 12 weeks, HR = 0.86, 95% CI 0.61-1.22; median OS, 15.0 vs 18.9 months, HR = 1.07, 95% CI 0.72-1.58). Toxicity profiles were similar in both arms and all were manageable.
CONCLUSIONS
Lapatinib plus vinorelbine treatment was tolerable; however, it failed to demonstrate the clinical benefits over vinorelbine alone in patients with HER2 + MBC after progression on both trastuzumab and lapatinib.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov number NCT01730677.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Disease-Free Survival; Female; Humans; Lapatinib; Middle Aged; Neoplasm Metastasis; Receptor, ErbB-2; Trastuzumab; Vinorelbine
PubMed: 31690831
DOI: 10.1038/s41416-019-0618-z -
JAMA Network Open Mar 2020There is currently no standard treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) without driver gene variation after failure of 2 or more...
Efficacy and Safety of Apatinib Plus Vinorelbine in Patients With Wild-Type Advanced Non-Small Cell Lung Cancer After Second-Line Treatment Failure: A Nonrandomized Clinical Trial.
IMPORTANCE
There is currently no standard treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) without driver gene variation after failure of 2 or more lines of chemotherapy.
OBJECTIVE
To assess the efficacy and safety of apatinib combined with oral vinorelbine.
DESIGN, SETTING, AND PARTICIPANTS
This phase 2 prospective nonrandomized clinical trial evaluating the efficacy and safety of apatinib plus vinorelbine recruited patients from Hunan Cancer Center, Hunan, China, from January 1, 2017, to November 30, 2018. Eligible patients were those with wild-type advanced NSCLC whose disease did not respond to at least 2 lines of chemotherapy. Patients were evaluated until December 31, 2019. Data were analyzed from July 2019 to December 2019.
INTERVENTION
Apatinib at an initial dose of 500 mg once daily and oral vinorelbine 60 mg/m2 once weekly were administered until disease progression, patient withdrawal, or occurrence of unacceptable toxic effects.
MAIN OUTCOMES AND MEASURES
The primary end point was overall response rate. Secondary end points were overall survival, progression-free survival, and safety.
RESULTS
The potential efficacy of apatinib plus vinorelbine was identified using drug susceptibility assay based on 3-dimensional coculture of tumor cells derived from 3 patients with lung adenocarcinoma. Among 30 patients enrolled, the median (range) age was 63 (34-78) years and 18 (60%) were men. Most patients (27 patients [90%]) had stage IV disease, and the median (range) number of prior unsuccessful treatments was 2 (2-5) lines of chemotherapy. Twenty-five patients (83%) completed the treatment, while 5 patients (17%) discontinued treatment owing to intolerable adverse events. The overall response rate was 36.7% (11 patients) and the disease control rate was 76.7% (23 patients). The median progression-free survival was 4.5 (95% CI, 2.4-6.6) months, and the median overall survival was 10.0 (95% CI, 4.8-17.1) months. Hand-foot syndrome was the most common adverse event observed, including grade 3 hand-foot syndrome observed in 5 patients (17%) and grade 4 hand-foot observed in 1 patient (3%). Grade 3 weakness was observed in 1 patient (3%).
CONCLUSIONS AND RELEVANCE
These findings suggest that apatinib combined with oral vinorelbine is a potentially effective regimen with an acceptable safety profile. This regimen may have potential as a treatment option for patients with wild-type advanced NSCLC whose disease failed at least 2 prior lines of chemotherapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03652857.
Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Progression-Free Survival; Prospective Studies; Pyridines; Treatment Outcome; Vinorelbine
PubMed: 32191330
DOI: 10.1001/jamanetworkopen.2020.1226 -
The Eurasian Journal of Medicine Feb 2020This study investigated pre- and post-treatment tumor and lymph node dimension response rates and differences between side-effect profiles in patients with locally...
OBJECTIVE
This study investigated pre- and post-treatment tumor and lymph node dimension response rates and differences between side-effect profiles in patients with locally advanced inoperable nonsmall-cell lung cancer (NSCLC) receiving radiotherapy (RT) and concurrent chemotherapy (CT).
MATERIALS AND METHODS
A total of 30 inoperable patients who had not previously received RT and having a mean age of 58.73±8.65 years with sufficient hematological reserves and normal hepatic and renal functions were included in the study. Those with pleural effusion, supraventricular lymph node metastasis, and N3 lymph node involvement were excluded. Group I (n=15) received a 21-day 75 mg/m cisplatin (D1) and 15 mg/m vinorelbine (D1, D8), whereas Group II (n=15) received 45 mg/m2 paclitaxel and AUC2 carboplatin weekly. RT was administered using a linear accelerator device with the 3D conformal RT technique at 6-18 MV energy with a 1.8-2 Gy fraction for 6-7 weeks.
RESULTS
Patients were randomized into Group I receiving RT and concurrent cisplatin-vinorelbine and Group II receiving weekly paclitaxel-carboplatin CT. Pre- and post-treatment tumor and lymph node dimensions significantly differed in both groups (p<0.001 and p<0.01, respectively). No significant change was observed in post-RT tumor and lymph node dimensions in terms of applied CT regimens (p>0.05).
CONCLUSION
The significant response achieved with concurrent RT and CT in groups I and II in the local advanced stage of NSCLC is important for local tumor control. Responses to treatment in the group of two arms did not differ.
PubMed: 32158319
DOI: 10.5152/eurasianjmed.2019.19136 -
Heliyon Nov 2023The high incidence and severe clinical manifestations of phlebitis pose a complex and urgent clinical challenge. The rapid and simple establishment of animal phlebitis...
BACKGROUND
The high incidence and severe clinical manifestations of phlebitis pose a complex and urgent clinical challenge. The rapid and simple establishment of animal phlebitis models and the development of preventive strategies are crucial to resolving this problem.
METHODS
In this study, we established such models by mixing vinorelbine ditartrate (VNR) and carbomer to form a sustained-release gel carrier, and then injected it around the veins rather than inside the vessels. Furthermore, we analyzed the efficacy of the carbomer/VNR gel in inducing phlebitis by monitoring the morphology of the veins using HE staining, immunohistochemical and immunofluorescence staining, and western blotting. Reactive oxygen species (ROS) and lipid peroxidation levels were determined using flow cytometry. Finally, we evaluated the inhibitory effect of N-acetylcysteine (NAC) on VNR-induced phlebitis in rabbits and rats.
RESULTS
Our findings suggested that the carbomer/VNR gel rapidly and easily induced phlebitis due to by retention of the gel in situ, wrapping the veins, and the prolonged release of VNR. NAC alleviated the VNR-induced oxidative stress response and expression of inflammatory cytokines by attenuating mitochondrial damage in venous endothelial cells, thereby preventing the occurrence of phlebitis in rabbits and rats.
CONCLUSION
The in situ carbomer/VNR gel provides a rapid and simple method for establishing an animal model to study the pathogenesis of phlebitis. Furthermore, the observed therapeutic effect of NAC highlights its novel and efficacious role in preventing and treating phlebitis.
PubMed: 37942159
DOI: 10.1016/j.heliyon.2023.e21235