A multi-center single arm study of FOLFIRI combined with Apatinib on the treatment of non resectable metastatic colorectal cancer
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ABSTRACT:
DISEASE(S): Advanced Colorectal Cancer
PROVIDER: 2676687 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Purpose: Primary retroperitoneal liposarcomas (RLPSs) are rare heterogeneous tumors for which there are few effective therapies. Certain anti-angiogenic tyrosine kinase inhibitors have demonstrated efficacy against various solid tumors. The aims of this study were to investigate the effect of Apatinib against retroperitoneal liposarcoma cells and its underlying mechanism and to explore the anti-tumor efficacy of a combination of Apatinib and Epirubicin. Methods: SW872 cells were treated with Apatinib(18μM) for 24 h. The RNAs of the control group and experimental group were stored in TRIzol reagent at -80 ℃. Then mRNA extraction and RNA sequencing were performed by Beijing Mygenostics Co. Ltd., Beijing, China. A Bioanalyzer 2100 System (Agilent Technologies, Santa Clara, CA, USA) was used to assay RNA integrity. An AMPureXP system (BeckmanCoulter, Brea, CA, USA) was used to perform PCR on the products. Quality-tested library preparations were sequenced on the Illumina Novaseq platform (Illumina, San Diego, CA, USA). There were three biological replicates per condition. Differential expression analysis of both groups was performed using DESeq2R v. 1.20.0. The Benjamini-Hochberg multiple hypothesis test correction was performed to obtain the false discovery rate (FDR). The criteria used to select the DEGs were |log2(FoldChange)| > 0.5 and FDR < 0.05. When log2(FoldChange) > 0, the gene was considered upregulated. When log2(FoldChange) < 0, the gene was considered downregulated. profiler package in R (R Core Team, Vienna, Austria) was used for GO function and KEGG pathway enrichment analyses of the DEGs. Histograms and bubble graphs were plotted with the ggplot2 package in R v. 3.4.3. Results:To elucidate the mechanisms by which Apatinib inhibited liposarcoma cells, we used RNA-seq to evaluate relative genetic changes in the SW872 cells after being treated with Apatinib for 24 hs, and found 2,038 DEGs, including 1,059 significantly downregulated genes and 979 significantly upregulated genes. The output of the KEGG pathway enrichment analysis suggests that Apatinib might inhibit SW872 cell proliferation through p53, DNA replication, and other important signaling pathways. GO enrichment analysis was performed on the genes that were significantly altered after Apatinib application.High-throughput RNA sequencing showed that Apatinib downregulated the expression of TYMS and RRM2. Conclusions: Apatinib showed strong efficacy against liposarcoma both in vitro and in vivo. Apatinib might inhibit liposarcoma cell proliferation through the RRM2/PI3K/AKT/mTOR signaling pathway and downregulate PD-L1 via the TYMS/STAT3 signaling pathway.
2021-11-03 | GSE185783 | GEO
Project description:Interventions: Apatinib treatment group:Apatinib Tablets orally
Primary outcome(s): PFS;ORR
Study Design: Case series
| 2670828 | ecrin-mdr-crc
Project description:Targeted therapy for patients with EGFR mutations by tyrosine kinase inhibitors (TKIs) has provided a significant benefit to patients. However, gradually developed resistance to the therapy becomes a major challenge in clinical practice. Herein, we report that Apatinib, an anti-angiogenic drug, strongly and specifically inhibits Gefitinib-resistant cancer cells but not their parental sensitive cells. Gefitinib-resistant lung cancer cell line (PC9GR) was established from its parental sensitive line (PC9) with a traditional EGFR mutation after long time exposure to Gefitinib. The established PC9GR cells had over 250 fold increased resistance to Gefitinib than its sensitive parental PC9 cells. Apatinib demonstrated much stronger (~5 fold) growth inhibition on PC9GR cells than on PC9 and other lung cancer cell lines. This inhibition was mostly achieved through cell cycle rest in G1 phase as demonstrated by transcriptome and protein expression data. Oral intake of Apatinib in mouse model significantly inhibited establishment and growth of PC9GR implanted tumors. VEGFR2 phosphorylation in PC9GR tumors after Apatinib treatment was significantly reduced along with less micro-vessel formation. Apatinib may provide a benefit to patients with acquired resistance to TKI treatment.
2019-05-15 | GSE129221 | GEO
Project description:Angiogenesis inhibitors are of considerable interest for treating metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of apatinib in chemotherapy-refractory mCRC. Apatinib 500 mg was administered daily to patients who had progressed after two or more lines of standard fluorouracil-based chemotherapy. Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Overall, 48 patients were enrolled. ORR and DCR were 8.3% (4/48) and 68.8% (33/48), respectively. Median PFS and OS were 4.8 (95% confidence interval [CI], 3.653-5.887) and 9.1 months (95% CI, 5.155-13.045), respectively, and did not differ between subgroups stratified by previous anti-angiogenic therapies. The most prevalent grade 3-4 adverse events were hypertension (12.5%), hand-foot syndrome (HFS, 10.4%), thrombocytopenia (10.4%), and proteinuria (8.3%). Low baseline neutrophil/lymphocyte ratio (NLR, hazard ratios [HR], 0.619; P = 0.027), early carbohydrate antigen 19-9 (CA19-9) decrease (HR, 1.654; P = 0.016), and HFS (HR, 2.087; P = 0.007) were associated with improved PFS. In conclusion, apatinib monotherapy demonstrated encouraging efficacy with manageable toxicities in chemotherapy-refractory mCRC. Previous anti-angiogenic therapies did not influence outcomes. Baseline NLR, early CA19-9 decrease, and HFS could predict the efficacy of apatinib.
| S-EPMC7142071 | biostudies-literature
Project description:Interventions: single arm:camrelizumab combined with apatinib mesylate
Primary outcome(s): PFS
Study Design: Single arm
| 2690370 | ecrin-mdr-crc
Project description:BackgroundApatinib improves progression-free survival and overall survival with an acceptable safety profile in Chinese patients with chemotherapy-refractory advanced or metastatic gastric cancer. However, the efficacy and safety of apatinib are unclear for elderly patients. This study was undertaken to prospectively investigate the efficacy and safety of apatinib for elderly patients with unresectable advanced or metastatic gastric cancer, who experienced progression to at least one lines of chemotherapy.MethodsThis open-label, single-arm, phase II study enrolled patients aged ≥60 years with advanced gastric cancer, who experienced progression to one or more lines of chemotherapy at five centers in China. Patients received apatinib in an oral dose of 500mg or 250mg daily according to the research physicians' decision. The primary end point was progression-free survival, and the secondary end points were objective response rate, disease control rate, overall survival, and safety.ResultsForty-eight patients were enrolled between June 2017 and September 2019. The median age was 65.5 years (range 60-80 years). Twenty-seven patients (56.3%) started treatment with an initial dose of 500 mg and 21 patients (43.7%) with 250 mg. The median progression-free survival and overall survival were 3.00 months (95% confidence interval, 2.17-3.84) and 8.10 months (95% confidence interval, 4.35-11.85), respectively. The objective response rate and disease control rate assessed by the investigators were 16.7% and 72.9%, respectively. The common side effects were fatigue (58.3%), hypertension (47.9%), abdominal pain (33.3%), proteinuria (29.2%), leukopenia (22.9%), and neutropenia (20.8%). Hypertension (22.9%) was the major grade 3/4 toxicity.ConclusionThese data suggest that apatinib is effective and relatively tolerable for elderly patients with unresectable advanced or metastatic gastric cancer who have received at least first-line chemotherapy.
| S-EPMC8380789 | biostudies-literature
Project description:In an ongoing, open-label, single-arm phase II study ( NCT02927301 ), 181 patients with untreated, resectable, stage IB-IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14-28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches.
| S-EPMC9556329 | biostudies-literature
Project description:LESSONS LEARNED:Patients with metastatic colorectal cancer with good performance status or no liver metastasis could benefit from apatinib.Circulating tumor DNA abundance may be a predictor in serial monitoring of tumor load. BACKGROUND:Apatinib, an oral vascular endothelial growth factor (VEGF) receptor-2 inhibitor, has been approved as third-line treatment for metastatic gastric cancer in China. The aim of this study was to evaluate the efficacy and safety of apatinib, in the treatment of patients with refractory metastatic colorectal cancer after failure of two or more lines of chemotherapy. METHODS:In this open-label, single-arm, phase II study, patients with histological documentation of adenocarcinoma of the colon or rectum were eligible if they had received at least two prior regimens of standard therapies including fluoropyrimidine, oxaliplatin, and irinotecan. These patients were treated with apatinib in a daily dose of 500 mg, p.o., in the third-line or higher setting. Capture sequencing was dynamically performed to identify somatic variants in circulating tumor DNA (ctDNA) with a panel of 1,021 cancer-related genes. The primary endpoint was progression-free survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Interim analysis was applied as predefined. RESULTS:From June 1, 2016 to December 31, 2017, 26 patients were enrolled. The median PFS of the whole group was 3.9 months (95% confidence interval [CI]: 2.1-5.9). The median overall survival (OS) was 7.9 months (95% CI: 4.6-10.1+). Patients with performance status (PS) 0-1 had longer PFS than those with PS 2 (4.17 months vs. 1.93 months, p = .0014). Patients without liver metastasis also had longer PFS than those who had live metastasis (5.87 months vs. 3.33 months, p = .0274). The common side effects of apatinib were hypertension, hand-foot syndrome, proteinuria, and diarrhea. The incidence of grade 3-4 hypertension, hand-foot syndrome, proteinuria, and diarrhea was 76.92%, 11.54%, 73.08%, and 23.08%, respectively. All of the patients received dose reduction because of adverse effect. Results of capture sequencing showed APC, TP53, and KRAS were most frequently mutant genes. ctDNA abundance increased before the radiographic assessment in ten patients. CONCLUSION:Apatinib monotherapy showed promising efficiency for patients with refractory colorectal cancer, especially in patients with PS 0-1 or no liver metastasis. ctDNA abundance may be a predictor in serial monitoring of tumor load.
| S-EPMC6656475 | biostudies-literature
Project description:Objective: To compare the outcome of patients with colorectal cancer who treated with adjuvant therapy or Apatinib with adjuvant therapy postoperatively.
Language: English.
| 2250127 | ecrin-mdr-crc
Project description:Interventions: Case series:Mesylate Apatinib
Primary outcome(s): R0 resection rate;AE
Study Design: Case series
| 2676351 | ecrin-mdr-crc