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Objective To investigate the safety and efficacy of camrelizumab added to second-line therapy after drug- eluting bead transarterial chemoembolization (DTACE) combined with apatinib for unresectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 89 HCC patients with camrelizumab added to second-line therapy who attended The First Affiliated Hospital of Zhengzhou University from December 2019 to December 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) after the application of camrelizumab, and the secondary endpoints were objective remission rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). The Kaplan-Meier method was used to plot survival curves, the Log-rank test was used for stratified analysis of subgroups based on baseline characteristics, and the influencing factors for prognosis were analyzed. Results A total of 89 patients were screened and followed up in this study. The patients were followed up to December 2021, with a median follow-up time of 16 months, a median OS time of 17.0 (95% confidence interval [ CI ]: 15.3-18.7) months, and a median PFS time of 7.0 (95% CI : 6.2-7.8) months. There were significant differences in OS and PFS between the patients with different ECOG-PS scores, liver function Child-Pugh classes, portal vein invasion, patterns of progression, times of DTACE treatment, durations of oral administration of apatinib, and durations of application of camrelizumab (all P 4 months had significant improvements in median OS [21.0 (95% CI : 19.1-22.9) months vs 14.0 (95% CI : 10.4-17.6) months, χ 2 =19.399, P 5 months had significant improvements in median OS [22.0 (95% CI : 20.2-23.8) months vs 13.0 (95% CI : 9.3-16.7) months, χ 2 =22.336, P < 0.001] and PFS [9.0 (95% CI : 7.0-11.0) months vs 5.0 (95% CI : 4.1-5.9) months, χ 2 =26.141, P < 0.001]. Post-embolization syndrome was the adverse event after DTACE and resolved after symptomatic treatment. Adverse reactions related to targeted drugs and immunotherapy all resolved after symptomatic supportive treatment, with no grade ≥4 adverse reactions, and no patients withdrew from target-free therapy due to TRAEs. Conclusion As for DTACE combined with apatinib in the treatment of unresectable HCC, camrelizumab added after progression has a marked therapeutic efficacy with safe and controllable TRAEs.
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Objective:To investigate the effect of apatinib and fluzoparib on the proliferation ability of cisplatin-resistant human ovarian cancer cells.Methods:Human ovarian cancer cells SKOV3 and cisplatin-resistant SKOV3/DDP cells of human ovarian cancer were treated with different concentrations of 1, 2, 4, 8, 16, 32, 64,128 μg/ml cisplatin at different times; CCK-8 method was used to detect the proliferation rate and half-inhibitory concentration ( IC50) of SKOV3 and SKOV3/DDP cells, and the drug-resistance fold of SKOV3/DDP cell was also calculated. SKOV3/DDP cells were treated with different concentrations of apatinib (4, 8, 16, 32, 64 μmol/L) and fluzoparib (148.15, 222.22, 333.33, 500.00, 750.00 μmol/L) for 24 h, 48 h and 72 h, respectively; the cell proliferation rate was determined by using CCK-8 method and IC50 was calculated. SKOV3/DDP cells were divided into the blank control group (cells untreated with drugs), cisplatin group, cisplatin + apatinib group, cisplatin + fluzoparib group, cisplatin + fluzoparib + apatinib group, and drug intervention was given in each group; the inhibition rate of cells in each group was detected by using CCK8 method. Results:The proliferation rate of SKOV3 cells treated with the same concentration of cisplatin for the same time was lower than that of SKOV3/DDP cells, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 4, 8, 16, 32, 64 μmol/L apatinib was 742.1μmol/L at 24 h, 156.8 μmol/L at 48 h, and 77.5 μmol/L at 72 h. Compared with the control group, the proliferation rate of SKOV3/DDP cells treated with apatinib at an effective concentration greater than 32 μmol/L was significantly decreased, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 148.15, 222.22, 333.33, 500.00, 750.00 μmol/L fluzoparib was 878.5 μmol/L at 24 h, 406.7 μmol/L at 48 h, and 283.3μmol/L at 72 h. When the effective concentration of fluzoparib was more than 333.33 μmol/L for 24 h, the proliferation rate of SKOV3/DDP cells was lower than that of the control group, and the differences were statistically significant (all P < 0.05). Compared with the control group, the proliferation rate of SKOV3/DDP cells was decreased when the effective concentration was more than 148.15 μmol/L at 48 h and 72 h, and the differences were statistically significant (all P < 0.05). The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib group was lower than that of 5 μg/ml cisplatin group [(40.4±1.4)% vs. (62.7±1.4)%, t = 20.22, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(5.2±0.4)% vs. (62.7±1.4)%, t = 52.04, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(0.3±0.8)% vs. (62.7±1.4)%, t = 53.98, P < 0.001]. The 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group had the lowest proliferation rate of SKOV3/DDP cells, which was lower than that of 5μg/ml cisplatin + 64 μmol/L apatinib group and 5 μg/ml cisplatin + 290 μmol/L fluzoparib group (all P < 0.001). Conclusions:Apatinib and fluzoparib can enhance the sensitivity of human ovarian cancer cisplatin-resistant cells SKOV3/DDP to cisplatin, and the combination of drugs can produce the stronger inhibitory effects and reverse cisplatin resistance of ovarian cancer.
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Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.
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Objective:To verify the transforming therapeutic efficacy of apatinib combined with oxaliplatin + tegiol (SOX regimen) in advanced gastric cancer with peritoneal metastasis.Methods:Using the method of descriptive case series study, the data of gastric cancer patients with peritoneal metastasis treated in Zhejiang Provincial People′s Hospital and Shulan (Hangzhou) Hospital from March 2016 to August 2021 were collected and treated with apatinib combined with SOX regimen. Oxaliplatin 130 mg/m 2, intravenous drip, day 1; Apatinib mesylate tablets 500 mg/d, oral, once a day, 1-21 days; Teggio: calculate the dosage according to the body surface area (<1.25 m 2, 40 mg; 1.25-1.50 m 2, 50 mg; >1.50 m 2, 60 mg). Take it orally for 1-14 days, twice a day. From the first day of chemotherapy, a cycle of 3 weeks. The short-term efficacy was evaluated every 2 cycles. After that, the multidisciplinary treatment team will decide whether the conversion operation can be accepted. When the requirements of surgical resection were met, the operation will be carried out after 1 cycle of drug withdrawal. Results:The median survival time (MST) of 23 patients was 14.1 months (95% CI: 12.3-16.4); The median overall survival (OS) after transformation therapy was 19.1 months (95% CI: 15.5-22.8). After transformation therapy, 14 cases of partial remission (PR), 3 cases of stable disease (SD) and 6 cases of progression disease (PD) in 23 patients, and the objective remission rate (ORR) was 73.9%(17/23). 12(52.2%) patients underwent surgery after transformation therapy. The 1-year OS of 12 patients was (17.0±1.5)months; Among them, 5 cases underwent R0 resection, and the R0 resection rate was 5/12. Conclusions:Transformation treatment with apatinib combined with oxaliplatin + tegio (SOX regimen) in advanced gastric cancer can achieve a high R0 resection rate with better conversion effect.
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Objective:To explore the clinical efficacy and safety of the camrelizumab combined with apatinib and chemotherapy as second-line or later therapy in human epidermal growth factor receptor-2 (HER-2) negative advanced gastric cancer.Methods:A total of 66 patients with HER-2 negative advanced gastric cancer and first-line treatment failure in Shandong Cancer Hospital Affiliated to Shandong First Medical University from March 2018 to September 2021 were selected. They were divided into study group ( n=22) and control group ( n=44) according to the different treatment regimens. The patients in the study group were treated with camrelizumab combined with apatinib and chemotherapy, and the patients in the control group were treated with chemotherapy alone. The short-term efficacy, progression-free survival (PFS) , overall survival (OS) and the occurrence of adverse reactions were compared, and Cox regression analysis was used to analyze the influencing factors of prognosis. Results:After at least 2-4 cycles of treatment, the ORR in the study group and the control group were 9.1% (2/22) and 0 (0/44) respectively, with no statistically significant difference ( P=0.108) . DCR in the two groups were 77.3% (17/22) and 45.5% (20/44) respectively, with a statistically significant difference ( χ2=6.03, P=0.014) . The study group didn’t reach median OS and the median OS in the control group was 11.7 months, with no statistically significant difference ( χ2=1.59, P=0.207) . The study group didn’t reach median PFS and the median PFS in the control group was 3.2 months, with a statistically significant difference ( χ2=10.13, P=0.001) . Multivariate Cox regression analysis showed that treatment method was an independent influencing factor for PFS in patients with HER-2 negative advanced gastric cancer ( HR=0.33, 95% CI: 0.15-0.75, P=0.008) . In terms of adverse reactions, there was a statistically significant difference in the incidence of elevated alanine aminotransferase between the study group and the control group [31.8% (7/22) vs. 6.8% (3/44) , χ2=5.32, P=0.021]. There were no adverse-related deaths in both groups. Conclusion:Compared with chemotherapy alone, camrelizumab combined with apatinib and chemotherapy as a second-line or later therapy in HER-2 negative advanced gastric cancer can prolong PFS and improve DCR, but the incidence of elevated alanine aminotransferase increases significantly.
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Objective:To explore the clinical efficacy of different doses of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and the adverse reactions.Methods:A total of 69 patients with NSCLC diagnosed in the No. 901 Hospital of the Chinese People′s Liberation Army Joint Logistics Support Force were selected from January 2018 to June 2020, and were divided into chemotherapy alone group (docetaxel+ cisplatin was used), apatinib group A [apatinib (0.25 g)+ docetaxel+ cisplatin was used] and apatinib group B [apatinib (0.50 g)+ docetaxel+ cisplatin was used] according to random number table method, with 23 cases in each group. The objective response rate (ORR), disease control rate (DCR), median overall survival (OS), median progression-free survival (PFS), and incidences of adverse reactions were compared between the three groups of patients.Results:One patients in the apatinib group B withdrew from the study due to acute myocardial infarction. After 4 cycless of treatment, the ORR of the patients in the chemotherapy alone group, apatinib group A and apatinib group B were 17.39% (4/23), 47.83% (11/23) and 54.55% (12/22) respectively, with a statistically significant difference ( χ2=7.41, P=0.024). The ORR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference ( χ2=6.77, P=0.009). There were no statistically significant differences in ORR between the apatinib group A and chemotherapy alone group, the apatinib group A and apatinib group B ( χ2=4.85, P=0.028; χ2=0.20, P=0.652). The DCR of the patients in the three groups were 47.83% (11/23), 78.26% (18/23) and 86.36% (19/22) respectively, with a statistically significant difference ( χ2=9.03, P=0.011). The DCR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference ( χ2=7.52, P=0.006). There were no statistically significant differences in DCR between the apatinib group A and the chemotherapy alone group, the apatinib group A and apatinib group B ( χ2=4.57, P=0.033; χ2=0.51, P=0.477). The median OS of the patients in the three groups were 6.8, 9.2 and 9.9 months respectively, with a statistically significant different ( χ2=8.91, P=0.022). Compared with the chemotherapy alone group, the median OS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences ( χ2=7.25, P=0.036; χ2=8.60, P=0.029). Compared with the apatinib group A, the median OS of the apatinib group B was prolonged, but there was no statistically significant different ( χ2=1.54, P=0.201). The median PFS of the patients in the three groups were 5.2, 7.7 and 8.2 months respectively, with a statistically significant different ( χ2=8.79, P=0.026). Compared with the chemotherapy alone group, the median PFS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences ( χ2=7.01, P=0.039; χ2=8.36, P=0.031). Compared with the apatinib A group, the median PFS of the apatinib group B was prolonged, but there was no statistically significant different ( χ2=1.68, P=0.186). There were statistically significant differences in the incidences of fatigue [34.78% (8/23) vs. 65.22% (15/23) vs. 72.73% (16/22), χ2=7.50, P=0.024], hypertension [4.35% (1/23) vs. 34.78% (8/23) vs. 68.18% (15/22), χ2=20.07, P<0.001], hand-foot syndrome [4.35% (1/23) vs. 43.48% (10/23) vs. 72.73% (16/22), χ2=22.28, P<0.001] and oral mucositis [8.70% (2/23) vs. 39.13% (9/23) vs. 72.73% (16/22), χ2=19.26, P<0.001] among the three groups. Compared with the chemotherapy alone group, the incidences of hypertension and hand-foot syndrome in the apatinib group A and the incidences of fatigue, hypertension, hand-foot syndrome and oral mucositis in the apatinib group B were increased, with statistically significant differences ( χ2=6.77, P=0.009; χ2=9.68, P=0.002; χ2=6.51, P=0.011; χ2=20.00, P<0.001; χ2=22.37, P<0.001; χ2=19.21, P<0.001). Conclusion:Apatinib (0.50 g) combined with chemotherapy has better short-term efficacy than chemotherapy alone in advanced NSCLC. Apatinib (0.25 g) and apatinib (0.50 g) can prolong the survival of patients, but increasing the treatment dose can not achieve longer survival benefit.
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Objective:To investigate the efficacy and safety of sindilizumab combined with apatinib in the treatment of elderly patients with advanced recurrent and metastatic esophageal squamous cell carcinoma.Methods:A total of 74 elderly patients with recurrent and metastatic esophageal squamous cell carcinoma who were admitted to Xuancheng City Central Hospital from March 2019 to August 2020 were selected, and they were divided into study group and control group by random number table method, with 37 cases in each group. The control group was treated with apatinib mesylate, and the study group was treated with sindilizumab combined with apatinib mesylate. All patients were treated for 2 cycles and followed up for 1 year. The efficacy, peripheral blood tumor marker levels, adverse reactions and survival were compared between the two groups.Results:The objective response rate and clinical control rate in the study group were higher than those in the control group [35.1% (13/37) vs. 13.5% (5/37), 67.6% (25/37) vs. 43.2% (16/37)], and the differences were statistically significant ( χ2 = 4.70, P = 0.030; χ2 = 4.43, P = 0.035). After treatment, the levels of carcinoembryonic antigen (CEA), squamous cell carcinoma-associated antigen (SCC-Ag) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in the two groups were all lower than those before treatment (all P < 0.05); the levels of CEA, SCC-Ag and CYFRA21-1 in the study group were lower than those in the control group (all P < 0.05). There were no differences in the incidence rates of fatigue, proteinuria, bone marrow suppression, and hand-foot syndrome between the two groups (all P > 0.05). After 1 year of follow-up, 20 patients in the study group survived, and the 1-year overall survival (OS) rate was 54.1%; 10 patients in the control group survived, and the 1-year OS rate was 28.6%; the difference in OS between the two groups was statistically significant ( χ2 = 4.06, P = 0.044). Conclusions:Sintilimab combined with apatinib has a good efficacy in the treatment of elderly patients with advanced recurrent and metastatic esophageal squamous cell carcinoma. This regimen can reduce the levels of tumor markers, improve the short-term survival rate of patients, and has good safety.
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Objective:To compare the clinical efficacy and safety of continuous dosing or alternate-day dosing of apatinib combined with SOX regimen as first-line treatment for patients with advanced gastric cancer.Methods:A total of 52 patients with human epidermal growth factor receptor 2 (HER2) negative and inoperable locally advanced or advanced gastric cancer who were pathologically diagnosed from January 2018 to January 2021 in the Second Affiliated Hospital of Shandong First Medical University were collected. The patients were divided into continuous dosing group and alternate-day dosing group by random number table method. The continuous dosing group received apatinib (250 mg, once a day) combined with SOX regimen (S-1+oxaliplatin); the alternate-day dosing group received apatinib (250 mg, once every other day) combined with SOX regimen. Twenty-one days were a cycle, and the efficacy was evaluated after 2 cycles. After 4-6 cycles, patients with stable disease received apatinib and S-1 for maintenance therapy. The therapeutic effects and adverse reactions of the two groups were compared.Results:The curative effect could be evaluated in 51 patients, including 26 in the continuous dosing group and 25 in the alternate-day dosing group. The disease control rates in the continuous dosing group and the alternate-day dosing group were 84.6% (22/26) and 76.0% (19/25) ( χ2 = 0.60, P = 0.499), and the median progression-free survival time was 7.50 months (95% CI 6.17-8.83 months) and 8.30 months (95% CI 6.99-9.61 months) ( χ2 = 0.71, P = 0.401), and the median overall survival time was 15.50 months (95% CI 11.30-19.69 months) and 15.60 months (95% CI 13.63-17.57 months) ( χ2 = 1.82, P = 0.177). The main adverse reactions in the two groups were leukopenia, thrombocytopenia, hypertension, nausea, vomiting, fatigue, hand-foot syndrome, proteinuria, liver and kidney damage. The incidence rates of ≥grade 3 adverse reactions in the continuous dosing group and the alternate-day dosing group were 42.3% (11/26) and 12.0% (3/25), and the difference was statistically significant ( χ2 = 4.46, P = 0.035). Conclusions:The efficacy of continuous dosing or alternate-day dosing of apatinib combined with SOX regimen as first-line treatment for advanced gastric cancer is similar, but the incidence of ≥grade 3 adverse reactions in alternate-day dosing group is lower, which improves the compliance and tolerance of patients.
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Lung cancer is the most common malignant tumor. As the first-generation oral small-molecule tyrosine kinase inhibitor independently developed in China, apatinib can block many kinds of signaling pathways with high selectivity, and play an anti-tumor effect by inhibiting tumor angiogenesis, and the adverse reactions are controllable. More and more studies have shown that apatinib can be used for the second-line and beyond treatment of patients with advanced non-small cell lung cancer. This article reviews the mechanisms and clinical studies of apatinib in treatment of lung cancer.
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Ovarian cancer (OC) has the highest mortality rate among gynecological malignancies. Its treatment has always been a difficult problem and the focus of exploration in the medical field. In recent years, anti-angiogenic drugs have shown good anticancer effects in the treatment of ovarian cancer. As a new generation of antiangiogenic drugs, apatinib has been proved to have a good therapeutic effect in the treatment of ovarian cancer with less adverse reactions. Therefore, we review the research progress of apatinib in ovarian cancer.
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Objective:To observe the efficacy of apatinib combined with first-line chemotherapy and maintenance therapy of only apatinib in patients with extensive small-cell lung cancer.Methods:The clinical data of 56 newly diagnosed patients with extensive small-cell lung cancer in the Fifth People′s Hospital of Dalian City from January 2018 to June 2019 were retrospectively analyzed. Among them, 27 patients (experimental group) were treated with first-line chemotherapy combined with apatinib, and 29 patients (control group) were treated with first-line chemotherapy alone. In experimental group, the expression levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)-2 1 day before chemotherapy and 1 day after chemotherapy were detected by enzyme linked immunosorbent assay method. Response evaluation criteria in solid tumor (RECIST) was used to evaluate the efficacy. The occurrence of adverse reaction was recorded. The patients were followed up for 12 to 24 months, and progression-free survival and 1-year survival were recorded.Results:The objective response rate, median progression-free survival time and 1-year survival rate in experimental group were significantly higher than those in control group: 81.5% (22/27) vs. 55.2% (16/29), 10.5 months vs. 8.5 months and 81.5% (22/27) vs. 55.2% (16/29), and there were statistical differences ( P<0.05); there was no statistical difference in disease control rate between 2 groups ( P>0.05). In experimental group, the patients with complete response and partial response after chemotherapy were classified as effective subgroup (22 cases), and the patients with stationary disease and progressive disease were classified as ineffective subgroup (5 cases). There were no statistical difference in VEGF and VEGFR-2 before chemotherapy between 2 subgroups ( P>0.05). The VEGF and VEGFR-2 in effective subgroup were significantly lower than those in ineffective subgroup: (275.34 ± 16.15) ng/L vs. (330.24 ± 23.21) ng/L and (89.35 ± 4.34) ng/L vs. (112.34 ± 5.45) ng/L, and there were statistical differences ( P<0.01). There were no uncontrollable adverse reactions in 2 groups, and there was no statistical difference in the incidence of adverse reactions between 2 groups ( P>0.05). Conclusions:Application of apatinib in first-line therapy and maintenance therapy for patients with extensive small-cell lung cancer can improve clinical efficacy and survival benefit with controllable adverse reactions.
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Objective:To evaluate the efficacy and safety of the combination of apatinib and S-1 for treatment of patients with advanced gastric cancer, in order to provide clinical therapy reference for advanced gastric cancer.Methods:Clinical trials were retrieved from China National Knowledge Infrastructure (CNKI) , Chinese Science and Technology Journal Database (CSTJ) , Wanfang Medical Network, VIP Journal Database (VIP) , China Biomedical Literature Database (CBMdisc) , Cochrane Library, PubMed, etc., searched from Jan. 2010 to Oct. 2019. The experimental group were given apatinib combined with S-1, and the control group received S-1 monotherapy. Two sets of RCT in patients with advanced gastric cancer were collected. Researchers first screened literature, data extraction and to assess the risk of bias, then made Meta analysis with RevMan5.3 software, the test level was α=0.05.Results:A total of 12 Meta analysis of randomized RCT were selected from the group, including 561 cases of patients. The results showed that objective response rate (ORR) and disease control rate (DCR) of the experimental group was higher than those of the control group [ (RD=0.16, 95% CI: 0.08-0.23, P<0.0001; RD=0.21,95% CI: 0.14-0.29, P<0.00001) ]; There was no significant difference in nausea and vomiting, hand-foot syndrome, fatigue, diarrhea, thrombocytopenia, neutropenia, leukopenia, neuro-toxicity and mucositis between the two groups. The rate of hypertension, proteinuria, hemoglobin of the experimental group decrease was higher than that of the control group [ (OR=6.21, 95% CI: 1.92-20.13, P=0.002; OR = 10.57,95% CI: 5.06-22.04, P<0.00001; OR=2.84, 95% CI:1.25-6.48, P=0.01) ]; and there was a significant heterogeneity in hypertension among them ( P=0.008, I 2=63) . Conclusion:Compared with S-1 alone, the treatment effect of S-1 combined with targeted drug apatinib can significantly improve ORR and DCR of patients with advanced gastric cancer.
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Objective To investigate the efficacy and safety of apatinib monotherapy as subsequent-line therapy on patients with advanced ESCC. Methods We included 56 patients with advanced ESCC who were administered with apatinib monotherapy. The initial dosage of apatinib was 500mg or 250mg daily. Clinicopathological characteristics, adverse reaction and prognosis of the patients were analyzed. The primary endpoint of this study was PFS, the secondary endpoints were ORR, DCR, OS and safety of apatinib administration. Results All the 56 patients with ESCC corresponded with the eligibility criteria and were available for the evaluation of efficacy and adverse reaction. The ORR of the 56 patients who received apatinib monotherapy was 8.9% (95%CI: 3.0%-19.6%) and DCR was 64.3% (95%CI: 50.4%-76.6%). The median PFS was 3.7 months (95%CI: 3.19-4.21) and the median OS was 6.3 months (95%CI: 3.53-9.08). The common adverse reactions were hypertension (50.0%), fatigue (41.1%), loss of appetite (35.7%), hand-foot syndrome (30.4%) and diarrhea (26.8%). Conclusion Apatinib monotherapy demonstrates potential efficacy and tolerable safety as the further-line treatment for the patients with advanced ESCC. And the conclusion should be validated in prospective clinical studies subsequently.
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Objective:To observe the efficacy of sintilimab combined with apatinib in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:Eighty-two patients with advanced NSCLC who were admitted to Nantong Cancer Hospital from October 2019 to September 2020 were selected for a prospective controlled study. They were divided into control group (treated with apatinib) and combination group (treated with sintilimab + apatinib) using the random number table method, with 41 cases in each group. The short-term clinical efficacy, tumor markers [neuron specific enolase (NSE), cytokeratin 19 fragment antigen (CYFRA21-1)], adverse reactions during treatment and survival were compared between the two groups.Results:The objective remission rate and clinical control rate in the combination group were higher than those in the control group [41.46% (17/41) vs. 19.51% (8/41), 85.37% (35/41) vs. 58.54% (24/41)], and the differences were statistically significant ( χ2 values were 4.66 and 7.31, both P < 0.05). The levels of NSE and CYFRA21-1 in the combination group were lower than those in the control group after treatment [(19.04±2.54) ng/ml vs. (21.35±3.11) ng/ml, (4.58±1.02) μg/L vs. (6.07±1.84) μg/L], and the differences were statistically significant ( t values were 3.68 and 4.54, both P < 0.001). There were no statistical differences in the incidence rates of gastrointestinal reaction, bone marrow depression, fatigue, and liver and kidney function damage between the combination group and the control group during treatment (all P > 0.05). The survival rate of the combination group was higher than that of the control group (71.79% vs. 47.50%), and the difference was statistically significant ( χ2 = 4.84, P = 0.028). Conclusions:Sintilimab combined with apatinib may improve clinical efficacy, reduce tumor marker levels, and improve short-term survival rate of advanced NSCLC patients.
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Objective:To observe the short- and long-term efficacy of apatinib combined with chemoradiotherapy in the treatment of advanced gastric cancer and its effect on tumor markers.Methods:From January 2013 to January 2017, 84 patients with advanced gastric cancer admitted to the Department of Oncology of Chang′an Hospital of Xi′an City were selected as the subjects. The patients were divided into synchronous chemoradiotherapy group and targeted chemoradiotherapy group by prospective nested control method, with 42 cases in each group. The synchronous chemoradiotherapy group was treated with synchronous chemoradiotherapy, and the targeted chemoradiotherapy group was treated with apatinib combined with chemoradiotherapy, 2 weeks was a cycle, a total of 12 cycles. The short- and long-term efficacy, median overall survival, changes of gastric cancer-related markers and adverse reactions of the two groups were compared.Results:After 3 months of treatment, there was no significant difference in the efficacy distribution between the synchronous chemoradiotherapy group and the targeted chemoradiotherapy group ( Z=0.240, P=0.887). The disease control rates of the two groups were 69.05% (29/42) and 73.81% (31/42) respectively, with no statistically significant difference ( χ2=0.233, P=0.629). After 6 months of treatment, the difference of the efficacy distribution between the synchronous chemoradiotherapy group and the targeted chemoradiotherapy group was statistically significant ( Z=6.288, P=0.043), and the disease control rates of the two groups were 42.86% (18/42) and 69.05% (29/42) respectively, with a statistically significant difference ( χ2=5.845, P=0.016). The median overall survival in the targeted chemoradiotherapy group and synchronous chemoradiotherapy groups were 18.7 months (95% CI: 8.4-24.8) and 13.8 months (95% CI: 7.2-18.7), with a statistically significant difference ( χ2=7.542, P<0.001). After 3 months of treatment, the levels of carbohydrate antigen (CA) 19-9, CA125, carcino-embryonic antigen (CEA) were (16.27±2.13) U/ml, (13.25±2.26) U/ml, (2.97±0.85) ng/ml in the targeted chemoradiotherapy group and (29.34±3.69) U/ml, (21.63±2.69) U/ml, (6.19±1.23) ng/ml in the synchronous chemoradiotherapy group respectively, all of them were lower than those before treatment, and the CA19-9, CA125, CEA in the targeted chemoradiotherapy group were lower than those in the synchronous chemoradiotherapy group, and there were statistically significant differences ( t=19.880, P<0.001; t=15.458, P<0.001; t=13.957, P<0.001). The total incidence of grade 3-4 adverse reactions in the targeted chemoradiotherapy group was 23.81% (10/42) and 28.64% (12/42) in the synchronous chemoradiotherapy group, and there was no statistically significant difference ( χ2=0.186, P=0.667). Conclusion:The long-term efficacy of apatinib combined with chemoradiotherapy in the treatment of advanced gastric cancer is better than that of synchronous chemoradiotherapy, and it is safe and reliable. At the same time, it can prolong the overall survival and reduce the levels of serum tumor markers.
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Objective: To investigate the efficacy and safety of paclitaxel combined with apatinib in comparison with paclitaxel alone as the second-line treatment for gastric cancer. Methods: Patients with advanced gastric cancer who had been treated at Chifeng Municipal Hospital, Chifeng Clinical Medical School of inner Mongolia Medical University, from March 2017 to March 2018 were enrolled. Inclusion criteria were human epidermal growth factor receptor-2(HER-2)-negative cancer and progression after the first-line treatment with fluorouracil combined with platinum. Patients were divided into groups administered with a single drug and combination of drugs. The single-drug group was administered with paclitaxel chemotherapy, while the combined-drug group with the paclitaxel combined with apatinib treatment. In both groups, the primary endpoint of observation was progression-free survival (PFS), while the secondary endpoint was the disease control rate (DCR), overall response rate (ORR), and safety. Results: A total of 60 patients were enrolled, including 30 patients in each of single- and combined-drug groups. PFS was significantly better in the combined-drug group than in the single-drug group (P0.05). The incidence of hypertension was significantly higher in the combined-drug group than in the single-drug group (P0.05). Conclusions: Paclitaxel combined with apatinib mesylate is superior to paclitaxel alone in the second-line treatment of gastric cancer. PFS, DCR, and ORR are superior with paclitaxel combined with apatinib mesylate than with paclitaxel alone. Although DCR and ORR in the combined-drug group were not significantly different from those in the single-drug group, the PFS was significantly longer in the combined-drug group, and the toxic and side effects of paclitaxel combined with apatinib mesylate were tolerable and safe.
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Objective To explore the effect of apatinib in first-line treatment of advanced liver cancer. Methods Retrospective analysis was performed on 35 patients with advanced liver cancer treated in our department from July 2017 to January 2020. All patients were given apatinib mesylate tablet 250-500 mg orally with QD. The patients with effective disease control (including CR, PR and SD) were given administration until PD or intolerance or death occurred. The primary endpoints were PFS and OS, and the secondary endpoints were DCR and ORR. The side effect was observed. Results There was one case of CR, 17 cases of PR and 11 cases of SD. The ORR and DCR were 51.43% and 82.86%. The median PFS and OS were 9.7 and 11.1 months. The main adverse reactions included hand-foot syndrome, hypertension, proteinuria, etc. Most grade 3-5 adverse reactions were reversible with good safety. Conclusion Apatinib can significantly improve the clinical benefits of liver cancer patients. It is an alternative first-line treatment for advanced liver cancer.
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In recent years, antiangiogenic drugs based on VEGF and VEGFRs signaling pathway have been widely used in the treatment of malignant tumors. Apatinib is an orally bioavailable small-molecule antiangiogenic agent and can specifically inhibit the tyrosine kinase activity of VEGFR, thereby inhibiting tumor angiogenesis. Apatinib is the first-level recommendation of third-line treatment of gastric cancer in CSCO Guidelines for the Diagnosis and Treatment of Gastric Cancer published in 2018. Apatinib has been proved to be effective and safe in gastric, lung and breast cancers. In addition, the drug shows great potential in the treatment of a variety of solid tumors. This article reviews the recent progress on the mechanism, clinical efficacy, related efficacy predictors of apatinib and its combination with other antitumor drugs.
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Objective: To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis. Methods: A prospective study "one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer" (clinical registration ChiCTR-ONC-17010430) from medical record database was retrospectively analyzed. Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration, and had not receive radiotherapy, chemotherapy, targeted therapy or immunotherapy before were enrolled. Before operation, the patients received 6 cycles of S-1 (80-120 mg/d, d1-d14) and oxaliplatin (130 mg/m(2), d1), and 5 cycles of apatinib (500 mg/d, d1-d21) conversion regimen. Three weeks after chemotherapy, whether the operation was performed or not depending on re-evaluation and patient preference. The main outcome were adverse reactions, and the secondary outcome were objective remission rate (ORR), disease control rate (DCR), and overall survival (OS) rate. The follow-up period was up to May 2020. Results: A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study. There were 13 males and 14 females, with a median age of 58 (30-68) years old. There were 9 cases of P1a, 5 cases of P1b, and 13 cases of P1c. There were 14 cases with 1-5 scores of PCI (peritoneal cancer index), and 13 cases with 6 scores or above. The incidence of adverse reactions was 100%. The most common adverse reactions were hematological events including leucopenia (70.4%, 19/27) and granulocytopenia (74.1%, 20/27). Non-hematological adverse events included fatigue (51.9%, 14/27) and oral mucositis (37.0%, 10/27). One patient was withdrawn due to grade 4 thrombocytopenia. Among 26 patients with feasible efficacy evaluation, 18 (69.2%) achieved partial remission, 3 (11.5%) achieved stable disease, and 5 (19.2%) disease progression. The objective remission rate was 69.2% (18/26) and the disease control rate was 80.8% (21/26). Fourteen patients underwent surgery, including 6 patients undergoing R0 resection with the R0 resection rate of 42.9% (6/14). The postoperative pathological response rate was 64.3% (9/14). The follow-up time was 12-40 months, and the follow-up rate was 100%. The 1-year OS rate was 65.2% and the survival time was (14.0±1.7) months. The 1-year OS rates of P1a/P1b group and P1c group were 81.8% and 42.0% respectively, whose difference was statistically significant (P=0.041). The 1-year OS rates of PCI 1-5 group and PCI ≥6 group were 67.3% and 38.5% respectively, whose difference was statistically significant (P=0.022). Conclusion: In the conversion treatment of gastric cancer peritoneal metastasis, the safety of apatinib combined with oxaliplatin and S-1 is acceptable, and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Oxaliplatin , Percutaneous Coronary Intervention , Peritoneal Neoplasms/drug therapy , Prospective Studies , Pyridines , Retrospective Studies , Stomach Neoplasms/drug therapyABSTRACT
Objective:To investigate the effect of apatinib on radiosensitivity of glioma cells U87MG and its potential mechanism.Methods:U87MG cells were divided into control group, apatinib group, radiation group and combination group treated with apatinib and radiation. The effect of different concentrations of apatinib (5, 10, 20, 40, 80 μmol/L) on cell proliferation was detected by CCK8 assay. The effect of apatinib on cell migration and invasion was detected by wound-healing assay and transwell assay, respectively. The effect of apatinib on cell radiosensitivity was detected by plate cloning assay, the cell apoptosis rate was detected by flow cytometry, and the protein expressions of Bax and Bcl-2 were detected by Western blot.Results:Apatinib significantly inhibited the proliferation of U87MG cells in a manner depended on the drug treatment time and radiation. Compared with the radiation group, the cell proliferation, migration and invasion in the combination group were inhibited much significantly ( t=9.857, 18.704, 4.197, P<0.05), so that the value of D0, Dq and SF2 of the combination group was lower, resulting in a radiosensitivity enhancement ratio (SER D0 ) of 1.3. Moreover, compared with the radiation group, the apoptosis rate of the combination group was increased, the expression of Bcl-2 protein was decreased, and the expression of Bax protein was increased ( t=16.187, 8.890, 5.222, P< 0.05). Conclusions:Apatinib inhibits cell proliferation, invasion and migration, induces apoptosis and increases radiosensitivity of glioma cells.