ABSTRACT
Objective:To investigate the effects of different chemotherapy dose intensity on the short-term efficacy and adverse reactions of patients with advanced colon cancer.Methods:A real-world database of patients with advanced colon cancer in Wangjing Hospital of China Academy of Chinese Medical Sciences and China-Japan Friendship Hospital from January 2017 to December 2020 was established, including 105 patients treated with the same chemotherapy regimen for two consecutive cycles. The patients were grouped according to the average relative dose intensity (ARDI) of chemotherapy, and the population differences, treatment regimens, short-term efficacy and adverse reactions of different chemotherapy dose intensities were evaluated. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of ARDI for short-term efficacy.Results:There were 31 patients in the high dose intensity group (ARDI≥80%) , 34 patients in the medium dose intensity group (80%<ARDI<60%) , and 40 patients in the low dose intensity group (ARDI≤60%) . There were statistically significant differences in age ( χ2=13.20, P=0.010) and Karnofsky functional status (KPS) score ( χ2=7.99, P=0.008) among the high dose intensity group, medium dose intensity group and low dose intensity group. Compared with the low dose intensity group, the proportion of young and middle-aged patients in the high dose intensity group was higher, and the proportion of elderly patients was lower ( χ2=12.63, P=0.002) . Compared with the medium dose intensity group, the proportion of patients with KPS score ≥60 was lower and the proportion of patients with KPS score <60 was higher in the low dose intensity group ( P=0.013) . There was a statistically significant difference in the application of chemotherapy regimen among the three groups ( χ2=22.88, P=0.027) , and there was a statistically significant difference in the application of chemotherapy regimen between the high dose intensity group and low dose intensity group ( χ2=16.25, P=0.009) . The proportions of the high, medium and low dose intensity groups receiving combined chemotherapy were 96.77% (30/31) , 82.35% (28/34) and 80.00% (32/40) respectively. The incidences of chemotherapy drug reduction in the high, medium and low dose intensity groups were 93.55% (29/31) , 100% (34/34) and 100% (40/40) respectively, and the incidences of chemotherapy delay were 41.94% (13/31) , 79.41% (27/34) and 87.50% (35/40) respectively. The objective response rates of the high, medium and low dose intensity groups were 22.58% (7/31) , 14.71% (5/34) and 2.50% (1/40) respectively, with a statistically significant difference ( χ2=7.11, P=0.027) . The disease control rates of the high, medium and low dose intensity groups were 93.55% (29/31) , 91.18% (31/34) and 87.50% (35/40) respectively, with no statistically significant difference ( χ2=0.75, P=0.714) . The differences of carcinoembryonic antigen before and after treatment in the high, medium and low dose intensity groups were 2.09, 0.47 and -0.72 ng/ml respectively, with a statistically significant difference ( χ2=10.09, P=0.006) . Compared with the low dose intensity group, the difference of carcinoembryonic antigen before and after treatment in the high dose intensity group was greater ( χ2=23.12, P=0.005) . The differences of carbohydrate antigen 199 before and after treatment in the high, medium and low dose intensity groups were 2.30, 0.00 and -0.21 U/ml respectively, with a statistically significant different ( χ2=8.85, P=0.012) . Compared with the low dose intensity group, the difference of carbohydrate antigen 199 before and after treatment in the high dose intensity group was greater ( χ2=21.40, P=0.010) . No adverse reactions above grade 3 occurred in the three groups, and the safety was good. The most common adverse reactions were anemia (61.90%, 65/105) , leucopenia (39.05%, 41/105) , neutropenia (29.52%, 31/105) and nausea (36.19%, 38/105) . There were no statistically significant differences in the incidences of adverse reactions among the high, medium and low dose intensity groups (all P>0.05) . ROC curve analysis found that the area under the curve predicting objective response was 0.70, the sensitivity was 92.30%, and the specificity was 52.10% when the chemotherapy ARDI threshold was 64%. Conclusion:In the real world, colon cancer patients receiving high dose intensive chemotherapy have better objective response rate, and tumor markers decreased significantly. The baseline status of colon cancer patients receiving low dose intensive chemotherapy is poor, but there is no statistically significant difference in disease control rate between patients receiving low dose intensive chemotherapy and patients receiving high dose intensive chemotherapy, and the adverse reactions are controllable.
ABSTRACT
Objective:Based on network pharmacology to study the mechanism of Shaoyao-Gancao Decoction in treating tension-type headache. Methods:Searched for the active ingredients and potential targets of Shaoyao-Gancao Decoction from TCMSP database, and adopted the targets of tension-type headache from GeneCards, DisGeNET, Drugbank and OMIM databases. Then obtained all the intersections of Shaoyao-Gancao Decoction and tension-type headache, and uploaded them to the STRING databases to construct a PPI network and conduct topological properties analysis. Finally, established a Chinese medicine regulatory network of Chinese medicine-components-target genes-disease by Cytoscape 3.6.1 software. To perform the GO function enrichment analysis and KEGG analysis on the core targets. Results:There were 51 intersections of Shaoyao-Gancao Decoction and tension-type headache. The topological properties analysis suggested that CASP3, JUN, HSP90AA1, MAPK1, STAT3, CCND1, ESR1, RELA, PTGS2, MAPK14 may be the potential targets for the treatment of tension-type headache in Shaoyao-Gancao Decoction. Gene ontology enrichment analysis showed 876 biological processes, 101 molecular functions and 62 cellular components. KEGG pathway enrichment analysis showed 25 related signaling pathways, including TNF signaling pathway, serotonergic synapse, NOD-like receptor signaling pathway, Dopaminergic synapse and Sphingolipid signaling pathway. Conclusion:The treatment of tension-type headache by Shaoyao-Gancao Decoction verified the characteristics of multi-component, multi-target and multi-pathway, which provided reference for the clinical medication.