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Brain Sciences Oct 2023To investigate the clinical impact of multiple courses of irradiation on pediatric patients with progressive diffuse intrinsic pontine glioma (DIPG), we conducted a...
To investigate the clinical impact of multiple courses of irradiation on pediatric patients with progressive diffuse intrinsic pontine glioma (DIPG), we conducted a retrospective case series on three children treated at our institution from 2018 to 2022. All children were candidates to receive systemic therapy with vinorelbine and nimotuzumab. Radiotherapy was administered to a total dose of 54 Gy. At any disease progression, our local tumor board evaluated the possibility of offering a new course of radiotherapy. To determine feasibility and assess toxicity rates, all children underwent clinical and hematological evaluation both during and after the treatment. To assess efficacy, all children performed contrast-enhanced MRI almost quarterly after the end of the treatment. In all children, following any treatment course, neurological improvement (>80%) was associated with a radiological response (41.7-46%). The longest overall survival (24 months) was observed in the child who underwent three courses of radiotherapy, without experiencing significant side effects. Even though it goes beyond the understanding of conventional radiobiology, first and second reirradiation in pediatric patients with progressive DIPG may represent a feasible and safe approach, capable of increasing overall survival and disease-free survival in selected patients and improving their quality of life.
PubMed: 37891817
DOI: 10.3390/brainsci13101449 -
Journal of Clinical Oncology : Official... Nov 2022Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from the concurrent BERNIE study.
PATIENTS AND METHODS
In MTS 2008, patients with metastatic RMS received four cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, five cycles of IVA, and 12 cycles of maintenance chemotherapy (low-dose cyclophosphamide and vinorelbine). The BERNIE study randomly assigned patients to the addition or not of bevacizumab to the same chemotherapy. Local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible.
RESULTS
MTS 2008 included 270 patients (median age, 9.6 years; range, 0.07-20.8 years). With a median follow-up of 50.3 months, 3-year event-free survival (EFS) and overall survival (OS) were 34.9% (95% CI, 29.1 to 40.8) and 47.9% (95% CI, 41.6 to 53.9), respectively. In pooled analyses on 372 patients with a median follow-up of 55.2 months, 3-year EFS and OS were 35.5% (95% CI, 30.4 to 40.6) and 49.3% (95% CI, 43.9 to 54.5), respectively. Patients with ≤ 2 Oberlin risk factors (ORFs) had better outcome than those with ≥ 3 ORFs: 3-year EFS was 46.1% versus 12.5% ( < .0001) and 3-year OS 60.0% versus 26.0% ( < .0001). Induction chemotherapy and maintenance appeared tolerable; however, about two third of patients needed dose adjustments during maintenance.
CONCLUSION
Outcome remains poor for patients with metastatic RMS and multiple ORFs. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies, with novel treatment approaches are urgently needed, to improve outcome for the group of patients with adverse prognostic factors.
Topics: Child; Humans; Disease-Free Survival; Antineoplastic Combined Chemotherapy Protocols; Rhabdomyosarcoma; Sarcoma; Ifosfamide; Vincristine; Cyclophosphamide; Dactinomycin; Doxorubicin; Neoplasms, Second Primary
PubMed: 35709412
DOI: 10.1200/JCO.21.02981 -
Cancer Medicine May 2023Patients with alveolar rhabdomyosarcoma (ARMS) have inferior outcomes compared to patients with embryonal rhabdomyosarcoma (ERMS) and more effective chemotherapy options... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with alveolar rhabdomyosarcoma (ARMS) have inferior outcomes compared to patients with embryonal rhabdomyosarcoma (ERMS) and more effective chemotherapy options are needed for these patients. Vinorelbine is a semisynthetic vinca alkaloid that has clinical activity in relapsed rhabdomyosarcoma (RMS) when used alone or in combination with cyclophosphamide.
AIMS
The goal of our study was to evaluate whether RMS histology subtype influences response rate to vinorelbine alone or in combination.
MATERIALS & METHODS
Five Phase 2 trials that enrolled RMS patients were included in the meta-analysis. Two studies evaluated vinorelbine alone, two studies evaluated vinorelbine in combination with low dose oral cyclophosphamide, and one study evaluated vinorelbine and intravenous cyclophosphamide in combination with temsirolimus or bevacizumab. All RMS patients had relapsed or refractory disease and had received at least one prior therapy. Response was reported according to RECIST1.1 and was defined as a complete or partial response. Response data was obtained from published results or from trial principal investigator. RMS NOS patients were grouped with ERMS patients for this analysis. Summary estimates comparing differences between ARMS and ERMS response rates were generated using a random-effects model to account for heterogeneity among the studies.
RESULTS
One hundred fifty-six enrolled patients evaluable for response were included in the meta-analysis, 85 ARMS, 64 ERMS and 7 RMS-NOS. The combined effect generated from the random-effects model demonstrated a 41% increase (p = 0.001, 95% CI; 0.21-0.60) in response to vinorelbine as a single agent or in combination in patients with ARMS compared to patients with ERMS. There was no significant difference in the rate of progressive disease between patients with ARMS compared to ERMS (p = 0.1, 95%CI; -0.26-0.02).
DISCUSSION
Vinorelbine is an active agent for the treatment of relapsed or refractory RMS and a meta-analysis of Phase 2 studies shows that radiographic responses in patients with ARMS were significantly higher than ERMS or RMS-NOS.
CONCLUSION
These data support further investigation of vinorelbine in newly diagnosed patients with RMS particularly those with alveolar histology.
Topics: Humans; Rhabdomyosarcoma, Embryonal; Rhabdomyosarcoma, Alveolar; Vinorelbine; Neoplasm Recurrence, Local; Rhabdomyosarcoma; Cyclophosphamide; Chronic Disease
PubMed: 37016270
DOI: 10.1002/cam4.5749 -
Frontiers in Oncology 2020The global COVID-19 pandemic has disrupted healthcare delivery, particularly for patients with advanced lung cancer. While certain aspects of care can be safely omitted... (Review)
Review
The global COVID-19 pandemic has disrupted healthcare delivery, particularly for patients with advanced lung cancer. While certain aspects of care can be safely omitted or delayed, systemic therapy plays an important role in survival and quality of life for patients with advanced lung cancer; limiting access to systemic therapy will compromise cancer-related outcomes. This can be at odds with strategies to mitigate risk of COVID-19 exposure, which include reducing hospital and clinic visits. One important strategy is implementation of oral cancer therapies. Many standard regimens require intravenous infusions but there are specific circumstances where an oral agent could be an acceptable alternative. Integrating oral therapeutics can permit patients to receive effective systemic treatment without the exposure risks associated with frequent infusions. Here, we review currently available oral cytotoxic agents with a potential role in the treatment of lung cancer.
PubMed: 32426292
DOI: 10.3389/fonc.2020.00793 -
Thoracic Cancer Aug 2023This single-arm prospective phase II trial was performed to assess the efficacy and safety of the dual oral metronomic vinorelbine and capecitabine (mNC) regimen in...
A phase II study of a doublet metronomic chemotherapy regimen consisting of oral vinorelbine and capecitabine in Chinese women with HER2-negative metastatic breast cancer.
BACKGROUND
This single-arm prospective phase II trial was performed to assess the efficacy and safety of the dual oral metronomic vinorelbine and capecitabine (mNC) regimen in women with HER2-negative metastatic breast cancer (MBC) in China.
METHODS
The mNC regimen was administered to the enrolled cases, including oral vinorelbine (VNR) 40 mg three times weekly (on days 1, 3 and 5 every week) and capecitabine (CAP) 500 mg three times a day, until disease progression or intolerable toxicity. The primary endpoint was the 1-year progression-free survival (PFS) rate. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and treatment-related adverse events (TRAEs). Stratified factors included treatment lines and hormone receptor (HR) status.
RESULTS
Between June 2018 and March 2023, 29 patients were enrolled into the study. The median follow-up time was 25.4 months (range, 2.0-53.8). In the entire group, the 1-year PFS rate was 54.1%. ORR, DCR and CBR were 31.0%, 96.6% and 62.1%, respectively. The mPFS was 12.5 months (range, 1.1-28.1). Subgroup analysis revealed that ORRs were 29.4% and 33.3% in first- and ≥second-line chemotherapy, respectively. ORRs were 29.2% (7/24) and 40.0% (2/5) for HR-positive MBC and metastatic triple-negative breast cancer (mTNBC), respectively. Grade 3/4 TRAEs were neutropenia (10.3%) and nausea/vomiting (6.9%).
CONCLUSIONS
The dual oral mNC regimen showed very good safety features and improved compliance without loss of efficacy in both first- and second-line treatments. The regimen also reached an excellent ORR in the mTNBC subgroup.
Topics: Humans; Female; Breast Neoplasms; Capecitabine; Vinorelbine; East Asian People; Prospective Studies; Vinblastine; Antineoplastic Combined Chemotherapy Protocols; Receptor, ErbB-2; Triple Negative Breast Neoplasms; Neoplasm Metastasis; Treatment Outcome
PubMed: 37402471
DOI: 10.1111/1759-7714.15011 -
Pharmacological Research Aug 2020Anaplastic thyroid cancer (ATC) is a rare neoplasia with a poor prognosis. Proliferation and apoptosis assays were performed on ATC cell lines (8305C, 8505C) exposed to...
Anaplastic thyroid cancer (ATC) is a rare neoplasia with a poor prognosis. Proliferation and apoptosis assays were performed on ATC cell lines (8305C, 8505C) exposed to vinorelbine, lenvatinib, as well as to concomitant combinations. ABCB1, ABCG2 and CSF-1 mRNA expression was evaluated by real time PCR. The relative levels of pospho Akt were investigated as part of a human phospho-kinase array analysis, and CSF-1 and VEGFR-2 protein levels were measured by ELISA. The intracellular concentration of lenvatinib in ATC cells was measured by combined reversed-phase liquid chromatography-tandem mass spectrometry. An ATC subcutaneous xenograft tumor model in nude mice was treated with vinorelbine, lenvatinib, or vinorelbine plus lenvatinib. After treatment with vinorelbine, lenvatinib, a significant antiproliferative effect in ATC cell lines was observed. The concomitant treatment of vinorelbine and lenvatinib revealed synergism for all the fractions of affected cells. A decrease in ABCB1 expression was reported in both ATC cell lines treated with the lenvatinib plus vinorelbine combination, as was an increase in the intracellular concentration of lenvatinib. The combination caused a decrease in Akt, GSK3α/β, PRAS40 and Src phosphorylation, and in both CSF-1 mRNA and protein levels. In the subcutaneous tumor model, the combination reduced the tumor volume during the treatment period. Our results establish the synergistic ATC antitumor activity of a vinorelbine and lenvatinib combination.
Topics: Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Male; Mice; Mice, Nude; Mice, Transgenic; Phenylurea Compounds; Quinolines; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Vinorelbine
PubMed: 32461187
DOI: 10.1016/j.phrs.2020.104920 -
NPJ Breast Cancer Sep 2022While therapies such as chemotherapy combined with immunotherapy, sacituzumab govitecan, and PARP inhibitors are available for metastatic TNBC, on disease progression...
While therapies such as chemotherapy combined with immunotherapy, sacituzumab govitecan, and PARP inhibitors are available for metastatic TNBC, on disease progression after these therapies, the mainstay of therapy is chemotherapy. Apatinib is a small-molecule tyrosine kinase inhibitor that has promising anti-angiogenesis and antitumor activity for TNBC. We aimed to evaluate the safety and efficacy of adding apatinib to chemotherapy in patients with advanced TNBC with failed first/second-line treatment. A total of 66 patients were randomly assigned, in a 1:1 ratio, to receive vinorelbine or vinorelbine with apatinib in 28-day cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. 33 received apatinib plus vinorelbine and 32 received vinorelbine (1 was withdrawal). Median PFS was significantly longer in the apatinib plus vinorelbine group than in the vinorelbine group (3.9 months vs. 2.0 months; hazard ratio, 1.82; 95% confidence interval [CI], 1.06 to 3.11; P = 0.026). Median OS was 11.5 months with apatinib plus vinorelbine and 9.9 months with vinorelbine (HR,1.01; 95% CI, 0.51 to 1.97; P = 0.985). The ORR was 9.1% in the apatinib plus vinorelbine group and 6.3% in the vinorelbine group (P = 0.667). The most common treatment-related hematologic grade 3-4 adverse events in apatinib plus vinorelbine group, were leukopenia, granulocytopenia, anemia, and thrombocytopenia. no treatment-related nonhematologic grade 4 adverse events or treatment-related deaths were observed. Collectively, adding apatinib to vinorelbine shows a promising benefit in PFS compared to vinorelbine monotherapy, with an excellent toxicity profile, warranting further exploration.
PubMed: 36127351
DOI: 10.1038/s41523-022-00462-6 -
BMC Medical Genomics Aug 2023To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2...
OBJECTIVE
To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2 and depths of various immune cell infiltration depths. The relationship between different immune checkpoints were also analyzed.
METHODS
First, the expression of EZH2 in pan-cancer (18 malignancies) was analyzed with the TCGA database. Hepatocellular carcinoma (HCC) tissues of 374 cases and normal tissues of 50 cases were analyzed in terms of the differential expression, overall survival (OS) and progression-free-survival (PFS). Then, we conducted GO and KEGG enrichment analysis on target gene. We also analyzed mRNA-miRNA and MicroRNA (miRNA)- long non-coding RNA (lncRNA) correlation with starbase databse, so as to determine the potential ceRNA mechanism associated with EZH2. Finally, immunoassay and drug-sensitivity analysis of EZH2 was performed.
RESULTS
Seven potential EZH2-related ceRNA pathways were screened out, namely lncRNA: Small Nucleolar RNA Host Gene 1 (SNHG1), SNHG 3, and SNHG 6-miR-101-3p-EZH2; and lncRNA: Long Intergenic Non-Protein Coding RNA 1978 (LINC01978), SNHG12, Ring Finger Protein 216 Pseudogene 1 (RNF216P1), and Coiled-coil Domain Containing 18 Antisense RNA 1 (CCDC18-AS1)-let-7c-5p-EZH2. Finally, 4 potential EZH2-related ceRNA pathways were identified through qPCR.According to immune correlation analysis, EZH2 may be positively correlated with T cells follicular helper, T cells Cluster of differentiation (CD)4 memory activated, Macrophages M0, and B cells memory (P < 0.05, cof > 0.2); while be negatively correlated with T cells CD4 + memory resting (P < 0.05, cof < -0.2). And EZH2 is positively correlated with Programmed Cell Death 1 (PDCD1) (R = 0.22), CD274 (R = 0.3) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (R = 0.23). According to drug sensitivity analysis, patients in the high expression group were more susceptible to the effects of various drugs including Sorafenib, 5-Fluorouracil, Doxorubicin, Etoposide, Paclitaxel, and Vinorelbine than those with low expression.
CONCLUSION
This study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p-EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Enhancer of Zeste Homolog 2 Protein; RNA, Long Noncoding; Liver Neoplasms; MicroRNAs; Immunoassay
PubMed: 37626362
DOI: 10.1186/s12920-023-01594-9 -
Blood Advances Apr 2022Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are...
Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are limited in this heavily pretreated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline-based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, <25 years of age, with relapsed/refractory AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate, defined as complete remission or complete remission with partial recovery of platelet count, was 71.4% (95% confidence interval [CI], 41.9-91.6) for those patients in first relapse (n = 14) and 47.4% (95% CI, 24.4-71.1) for patients in second or greater relapse or with refractory disease. Responses were seen across multiple high-risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year overall survival for patients in first relapse was 46.2% (95% CI, 19.1-73.3) and 50.0% (95% CI, 26.9-73.1) for patients who responded to TVTC. For pediatric and young adult patients with relapsed/refractory AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Child; Clofarabine; Humans; Leukemia, Myeloid, Acute; Recurrence; Thiotepa; Topotecan; Vinorelbine; Young Adult
PubMed: 35008101
DOI: 10.1182/bloodadvances.2021005753 -
Hereditas Jul 2023Copper-induced cell death (cuproptosis) is a new regulatory cell death mechanism. Long noncoding RNAs (lncRNAs) are related to tumor immunity and metastasis. However,...
BACKGROUND
Copper-induced cell death (cuproptosis) is a new regulatory cell death mechanism. Long noncoding RNAs (lncRNAs) are related to tumor immunity and metastasis. However, the correlation of cuproptosis-related lncRNAs with the immunotherapy response and prognosis of lung adenocarcinoma (LUAD) patients is not clear.
METHODS
We obtained the clinical characteristics and transcriptome data from TCGA-LUAD dataset (containing 539 LUAD and 59 paracancerous tissues). By utilizing LASSO-penalized Cox regression analysis, we identified a prognostic signature composed of cuproptosis-related lncRNAs. This signature was then utilized to segregate patients into two different risk categories based on their respective risk scores. The identification of differentially expressed genes (DEGs) between high- and low-risk groups was carried out using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We evaluated the immunotherapy response by analyzing tumor mutational burden (TMB), immunocyte infiltration and Tumor Immune Dysfunction and Exclusion (TIDE) web application. The "pRRophetic" R package was utilized to conduct further screening of potential therapeutic drugs for their sensitivity.
RESULTS
We ultimately identified a prognostic risk signature that includes six cuproptosis-related lncRNAs (AP003778.1, AC011611.2, CRNDE, AL162632.3, LY86-AS1, and AC090948.1). Compared with clinical characteristics, the signature was significantly correlated with prognosis following the control of confounding variables (HR = 2.287, 95% CI = 1.648-3.174, p ˂ 0.001), and correctly predicted 1-, 2-, and 3-year overall survival (OS) rates (AUC value = 0.725, 0.715, and 0.662, respectively) in LUAD patients. In terms of prognosis, patients categorized as low risk exhibited more positive results in comparison to those in the high-risk group. The enrichment analysis showed that the two groups had different immune signaling pathways. Immunotherapy may offer a more appropriate treatment option for high-risk patients due to their higher TMB and lower TIDE scores. The higher risk score may demonstrate increased sensitivity to bexarotene, cisplatin, epothilone B, and vinorelbine.
CONCLUSIONS
Based on cuproptosis-related lncRNAs, we constructed and validated a novel risk signature that may be used to predict immunotherapy efficacy and prognosis in LUAD patients.
Topics: Humans; Adenocarcinoma; Immunotherapy; Lung; Prognosis; RNA, Long Noncoding; Copper; Apoptosis
PubMed: 37482612
DOI: 10.1186/s41065-023-00293-w