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Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50％of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.
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OBJECTIVE To analyze the clinical characteristics of nephrotic syndrome induced by sunitinib， and to provide reference for clinical rational drug use. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， Web of Science and Medline， case report about sunitinib-induced nephrotic syndrome were collected from the inception to Oct. 30th， 2022. Those case reports were analyzed statistically in terms of gender， age， primary disease， drug use， clinical manifestations， treatment and outcome. RESULTS A total of 15 pieces of literature were collected and 17 patients were involved， including 10 males and 7 females. The average age of patients was （59.35±15.72） years. Among 17 patients， there were 10 patients with renal cell carcinoma and 7 patients with gastrointestinal stromal tumor， all of whom received evidence-based medication； the dosage of sunitinib in 15 cases was recorded， and all of them were within the recommended range of the instructions； 9 patients received combined therapy； the time from sunitinib application to the occurrence of nephrotic syndrome was 21 days-52 months， of which 11 cases were ≤2 years. The clinical manifestations in 13 patients were described， including edema， oliguria， foamy urine， weight gain， fatigue， dyspnea on exertion， etc. Eight patients had other adverse reactions induced by sunitinib before suffering from nephrotic syndrome， including new hypertension or worsening of original hypertension， and hand-foot syndrome. Renal biopsy mainly manifested as thrombotic microangiopathy， focal segmental glomerular sclerosis and immune complex glomerulonephritis. Sunitinib withdrawal or dosage reduction was adopted in all patients， and they were given symptomatic treatment such as glucocorticoids and antihypertensive agents. Symptoms of 16 patients were improved， and renal function of one patient deteriorated and hemodialysis was started. Sunitinib was re-challenged in 6 patients， elevated creatinine and substantial proteinuria recurred in 5 patients. CONCLUSIONS In clinical use of sunitinib， it is advisable to periodically monitor renal function. In case of deterioration of renal function， albuminuria， edema， etc.， relevant examinations should be implemented in time， and symptomatic intervention should be taken as soon as possible. Besides， we should be alert to the recurrence of nephrotic syndrome after sunitinib rechallenge.
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OBJECTIVE To study the role of phosphatidylinositol-3-kinase （PI3K） on sunitinib-induced myocardial systolic dysfunction. METHODS Using human-induced pluripotent stem cell-derived cardiomyocytes （hiPSC-CMS） as objects， the contractile force of cardiomyocytes was measured by CardioExcyte 96 system， and IC50 of sunitinib was calculated after hiPSC- CMS were treated with sunitinib at different concentrations [0 （control）， 0.5， 1， 3， 5， 10 μmol/L] for 24 hours. The effects of sunitinib （3.14 μmol/L） on the contractile frequency of cardiomyocytes， calcium transient amplitude and calcium transient recovery time course， mRNA expression of myocardial injury markers atrial natriuretic peptide （ANP）， brain natriuretic peptide （BNP） and β-myosin heavy chain （β-MHC） were detected. PI3K activator 3，4，5-triphosphate phos-phatidylinositol （PIP3， 1 μmol/L） and sunitinib were used to intervene in hiPSC-CMs jointly， so as to investigate the role of PI3K in the myocardial systolic dysfunction induced by sunitinib. RESULTS Sunitinib inhibited the contractile force of hiPSC-CMs in a concentration-dependent manner. IC50 of sunitinib was 3.14 μmol/L. After intervention with 3.14 μmol/L sunitinib， the contractile frequency of hiPSC-CMs and calcium transient amplitude were decreased significantly （P＜0.05 or P＜0.01）； the duration of calcium transient recovery was prolonged significantly （P＜0.05）， and mRNA expressions of ANP， BNP and β-MHC were significantly increased （P＜0.01）. After PI3K was activated with PIP3， the contractile force of hiPSC-CMs was increased significantly （P＜0.01）. CONCLUSIONS Activating PI3K activity is a potential molecular mechanism to improve myocardial toxicity induced by sunitinib.
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【Objective】 To systematically evaluate the efficacy and safety of targeted drugs in the treatment of metastatic non-clear cell renal cell carcinoma (nccRCC) and to provide guidance for clinical treatment. 【Methods】 All observational studies and randomized controlled trials (RCTs) of nccRCC treated with targeted drugs were retrieved from the PubMed, Embase, the Cochrane Library and Web of Science. Three independent investigators screened the literature, extracted data and evaluated the quality of literature. The RCTs were evaluated using the Cochrane Handbook. One research with insufficient outcome data (follow-up bias) was assessed as high risk, and the other studies showed low or uncertain risk. The non-RCTs were evaluated with the JBI Quality Assessment Tool, and all studies displayed a low risk of bias. The data were analyzed with Stata 17.0 software. 【Results】 A total of 16 studies involving 989 patients were included. Meta-analysis showed that the objective response rate (ORR) was 12.6% (95%CI:8.1%-17.9%), the total disease control rate (DCR) was 65.3% (95%CI:58.3%-72.1%), the total median progression-free survival (PFS) was 5.80 (95%CI:4.69-6.91) months, and the median overall survival (OS) was 15.93 (95%CI:12.17-19.68) months. In subgroup analysis, the total ORR of patients with metastatic nccRCC treated with sunitinib and cabozantinib were 11.7% (95%CI:6.5%-18.0%) and 17.2% (95%CI:8.4%-28.2%), respectively. The total ORR of patients with papillary renal cell carcinoma was 9.1% (95%CI:2.4%-18.9%). 【Conclusion】 Targeted drugs have a significant effect on patients with metastatic nccRCC, but adverse reactions may occur. Targeted drugs have poor effects on metastatic papillary renal cell carcinoma, and cabozantinib may have greater survival benefits.
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【Objective】 To explore the therapeutic effects of lactate dehydrogenase A (LDHA) inhibitor and targeted drugs on fumarate-hydratase-deficient renal cell carcinoma (FH-d RCC). 【Methods】 RNA-sequencing was used to detect the mRNA expression in FH-d RCC tissues, which was further validated with real-time fluorescence quantitative PCR and immunohistochemistry. Human-derived FH-d RCC cell line UOK262 and murine-derived FH-d RCC cell line FH1-/-CL19 (CL19) were treated with LDHA inhibitor [(R)-GNE-140] and listed kidney cancer targeted drugs (Axitinib, Cabozantinib, Sunitinib, Sorafenib, Pazopanib, Everolimus) respectively, and then treated with LHDA inhibitor in combination with the targeted drugs to observe the alteration of cell proliferation. The combination index (CI) of different dose groups of the combination drugs were analyzed with CompuSyn software to determine the optimal combination regimen. 【Results】 LDHA inhibitor and targeted drugs, including Cabozantinib, Sorafenib and Sunitinib, had a significant inhibitory effect on the proliferation of FH-d RCC cells, and the combination of Cabozantinib and Sorafenib or Pazopanib had a significant anti-tumor effect. 【Conclusion】 LDHA inhibitor combined with targeted drugs can significantly inhibit the growth of FH-d RCC cells, indicating that LDHA may be a potential therapeutic target of FH-d RCC.
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【Objective】 To analyze the correlation between the expressions of CD10,CA9 and CD133 and the prognosis of patients with metastatic renal clear cell carcinoma (mccRCC) treated with sorafenib or sunitinib. 【Methods】 A total of 80 mccRCC patients who received sorafenib or sunitinib as first-line therapy were retrospectively enrolled. Immunohistochemical staining (IHC) was performed for CD10,CA9 and CD133 in tumor tissue samples to analyze the correlation between the expression of each marker and clinicopathologic variables. Univariate and multivariate Cox proportional risk models were used to analyze prognostic factors of progression free survival (PFS) and overall survival (OS),and Kaplan-Meier survival analysis was performed for CA9 expression and PFS,OS in the treatment subgroups. 【Results】 Altogether 37 patients (46.25%) had PFS,and the median PFS (mPFS) was 24.9 months (95%CI:16.5-33.2 months),while 55 patients (68.75%) died and the median OS (mOS) was 44.2 months (95%CI:14.6-73.7). Low expression of CD10 was correlated with high Fuhrman grade (χ2=6.241,P=0.012),lymph node metastasis (χ2=5.952,P=0.015),and the number of metastatic organs ≥2 (χ2=8.205,P=0.004). Univariate analysis showed that Fuhrman grade,number of metastatic organs and lymph node metastasis were the prognostic factors of PFS (P<0.05),while the number of metastatic organs,lymph node metastasis and CA9 expression were the prognostic factors of OS (P<0.05). Multivariate analysis showed that Fuhrman grade was an independent factor of PFS (HR=2.457,95%CI:1.126-5.365,P=0.024),and the number of metastatic organs was an independent prognostic factor of OS (HR=1.857,95%CI:1.048-3.290,P=0.034). Survival analysis in subgroups showed that high CA9 expression in the sorafenib group was associated with longer OS (HR=0.401,95%CI:0.204-0.787,P=0.008). 【Conclusion】 Low expression of CA9 is an non-independent risk factor for OS,while CD10 and CD133 cannot be used as prognostic factors for mccRCC patients. Since mccRCC patients with low CA9 expression have less survival benefit from sorafenib and sunitinib,they can choose target therapy combined with immunotherapy or dual immunotherapy according to the guidelines to improve prognosis.
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@#Abstract: Objective To evaluate the effects of sunitinib on Japanese encephalitis virus (JEV) infection in vitro and vivo. Methods The 4-week-old BALB/c mice infected with JEV by intraperitoneal injection. The infected mice were treated with sunitinib for 5 days and 10 days respectively. After that, the change of weight and survival rate were evaluated continuously. The viral load variation in mice brain were detected by qRT-PCR. Indirect immunohistochemical staining assay (IFA) was used to detect the number and distribution of CD4+/CD8+T cells in mouse brain. IFA was also used to observe the expression of virus E protein in the brain of mice. Vero cells were infected with JEV in vitro and given a certain concentration of sunitinib to observe the cell survival status. The expression of virus E protein in cells was detected by IFA. Results Continuous administration of sunitinib significantly improved the survival rate of infected mice. Survival rate and body weight changes showed that the 5-day's administration strategy was significantly better than the 10-day's administration strategy. The treatment of sunitinib decreased the infiltration of CD4+/CD8+T cells in the brain and reduced the changes of vascular sleeve. However, the variation of viral load and E protein expression in brain were not obvious. The cytopathic effect (CPE) of infected Vero cells were slightly relieved after giving sunitinib, and the expression of E protein was also slightly changed. Conclusion Sunitinib can significantly reduce the mortality of infected mice, and the 5-day's administration strategy is significantly better than the 10-day's administration strategy. Sunitinib decrease T lymphocyte infiltration in brain of mice, relieve the encephalitis symptoms ,and prolonged the life of mice.
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Abstract Drug resistance is a crucial obstacle to achieve satisfactory chemotherapeutic effects. Numerous studies have shown that the PI3K/Akt signaling pathway plays a significant role in various processes of cellular events and tumor progression, while few studies have focused on the PI3K/Akt signaling pathway in drug resistance of endothelial cells. The present study aims to explore the relationship of PI3K/Akt signaling and cellular resistance to anticancer drugs in human microvessel endothelial cells (HMEC-1). We established stable sunitinib-resiatant human microvessel endothelial cells (HMEC-su) after long-term exposure to sunitinib (a small-molecule tyrosine kinase receptor inhibitor) for 12 months. HMEC-su showed significant alternations of cell morphology and exhibited a 2.32-fold higher IC50 of sunitinib than parental HMEC-1 cells. Expression of P-glycoprotein (P-gp) and breast cancer-resistance protein (ABCG2) which mediates drug efflux, increased significantly in HMEC-su lines compared with HMEC-1 cells by western blots assay. Our study further demonstrates that LY294002 (blocking the PI3K/Akt pathway) enhances the sensibility of HMEC-su to suntinib and inhibits the gene transcription and protein expression of P-gp, ABCG2 in HMEC-su cells. In conclusion, these results indicate that LY294002 could reverse P-gp and ABCG2 mediated-drug resistance to sunitinib in HMEC-su cells by inhibiting PI3K/Akt signaling.
Subject(s)
Drug Resistance , Endothelial Cells/classification , Pharmaceutical Preparations/administration & dosage , Blotting, Western/instrumentation , ATP Binding Cassette Transporter, Subfamily B, Member 1/adverse effects , Inhibitory Concentration 50 , Endothelial Cells/pathology , Sunitinib/agonistsABSTRACT
La osteonecrosis de los maxilares está definida como la exposición de hueso necrótico en la región maxilofacial al menos por ocho semanas en pacientes que están recibiendo medicamentos antirresortivos para el tratamiento del cáncer primario o metastásico hacia el hueso, osteoporosis o enfermedad de Paget, sin historia previa de radiación. Desde el año 2003, la terminología utilizada estaba en relación con los bifosfonatos, en la actualidad ha sido introducido el término osteonecrosis de los maxilares relacionada por medicamentos (OMAM). La cirugía oral (implantología o cirugía periapical) incrementa el riesgo de OMAM, así como los desbalances concomitantes de la salud oral (inflamación dental y formación de abscesos). Las estrategias conservadoras en el tratamiento varían desde el cuidado local conservador hasta la resección quirúrgica radical del hueso necrótico. En el presente artículo se expone un análisis sistemático retrospectivo de la literatura en páginas como PubMed, ScienceDirect y Springer, Cochrane Library. Con el objetivo de resaltar el aumento de la incidencia de OMAM a nivel mundial con el uso de antirresortivos y otros medicamentos asociados en su patogenia en el Hospital Regional «General Ignacio Zaragoza¼ del ISSSTE, UNAM, en la Ciudad de México (AU)
Osteonecrosis of the jaws is defined as the exposure of necrotic bone in the maxillofacial region for at least 8 weeks in patients receiving antiresorptive medications for the treatment of primary or metastatic cancer towards the bone, osteoporosis, or Paget's disease, without previous history of radiation. Since 2003, the terminology used was related to bisphosphonates, the term medication-related osteonecrosis of the jaws has now been introduced. Oral surgery (implantology or periapical surgery) increases the risk of avascular necrosis, as well as concomitant imbalances in oral health (dental inflammation and abscess formation). Conservative strategies in treatment vary from conservative local care to radical surgical resection of the necrotic bone. In this article, a systematic retrospective analysis of the literature is presented on pages such as PubMed, Science Direct and Springer, Cochrane Library. And in which the objective is to highlight the increase in the incidence of medication related osteonecrosis of the jaws worldwide with the use of antiresorptive, and other associated medications in its pathogenesis at the Hospital Regional «General Ignacio Zaragoza¼ ISSSTE, UNAM in Mexico City (AU)
Subject(s)
Humans , Diphosphonates/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw , Osteoporosis , Bone Neoplasms , Angiogenesis Inhibitors , Dental Service, Hospital , TOR Serine-Threonine Kinases , Bevacizumab , Sunitinib , MexicoABSTRACT
Objective: Tyrosine kinase inhibitors (TKIs) which efficiently inhibit BCR-ABL are highly effective for clinical treatment of chronic myeloid leukemia (CML), but development of resistance to TKIs is a big challenge to treatment. Sunitinib is a multitargeted TKI targeting vascular endothelial growth factor receptor and is defined a safe and effective candidate target, but its effect on other signaling pathways is unknown. To investigate the cytotoxic and apoptotic effect of sunitinib in CML cell model K-562 on JAK-STAT signaling pathway components, suppressor genes and oncogenes, hematopoiesis-related genes, cell cycle and VEGF pathway components, and mRNA level expression changes was aimed. Materials and Methods: Sunitinib's effective dose cytotoxic IC50 was determined by trypan blue and WST-1 cell proliferation assay tests. Expression levels of target genes were determined by quantitative reverse transcriptase polymerase chain reaction simultaneously after sunitinib application. Protein expression analysis was determined by “WesternBreeze Chromogenic Kit-Anti-Rabbit” based on the principles of the application kit by Western blot analysis. Results: Assessing the cytotoxicity of K-562 cells following sunitinib treatment revealed that sunitinib decreased cell proliferation in a time- and dose-dependent manner. According to the sunitinib inhibition curve, IC50 dose was calculated as 3.5 μM at 48th h for K-562 cells and apoptosis assays pointed that sunitinib induces apoptotic cell death of leukemic cells at moderate levels. Conclusion: Our study supports that sunitinib might be used as a novel therapeutic target to trigger apoptosis in CML cells which in turn might accelerate therapeutic response in regard to inhibiting oncogenes and enhancing tumor suppressors in cooperation with cell cycle regulatory genes
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AIM: To establish a HPLC-UV method to determine sunitinib in rat plasma and mouse tissues, and to study its pharmacokinetics in rats and tissue distribution characteristics in mice. METHODS: The biotic samples were prepared by protein precipitation followed by a stereoselective analysis of sunitinib was achieved on Waters XBridgeTM C18 (4.6 mm×250 mm, 5 μm) with a mobile phase composing of methanol-0.02 mol/L sodium dihydrogen phosphate (70:30) at a flow rate of 1.0 mL/min. The detection wavelength was 310 nm, and the column temperature was 25 ℃. RESULTS: The calibration curve for rat plasma sunitinib was linear in the range of 0.019 2-15.34 μg/mL. The linear ranges in mice brain and kidney were 0.038 3-11.50 and 0.038 3-69.00 μg/mL, respectively. After intragastric administration of sunitinib at a dose of 20 mg/kg to rats, the pharmacokinetic characteristics were Tmax=9.0 h, Cmax=0.194 mg/L, t1/2=18.4 h, AUC(0-∞)=6.8 mg•L-1•h. And the absolute bioavailablity was 47.1%. It was indicated that sunitinib could permeate the blood brain barrier, but the concentration was lower in brain and higher in kidney. CONCLUSION: A HPLC-UV method for the determination of sunitinib in rat plasma and mouse tissues was established. The method is simple, rapid, reliable, and provides a reference for the clinical application of sunitinib.
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OBJECTIVE：To evaluate the economics of first-line therapy drug for metastatic renal cell carcinoma （mRCC）as sunitinib，sorafenib and pazopanib ，and to provide reference for the adjustment of medical insurance list and clinical medication decision. METHODS ：Using“metastatic renal cell carcinoma ”“mRCC”“sunitinib”“sorafenib”“pazopanib”“cost-effectiveness” “cost-utility”“cost-benefit”“economic analysis ”as the Chinese and English retrieval words ，relevant literatures published during Jan. 1st，2006 to Jul. 15th，2019 were retrieved from PubMed ，Web of Science ，the Cochrane Library ，CNKI，Wanfang database ， VIP. The literatures were screened according to inclusion and exclusion criteria . The quality of the included literatures was evaluated with CHEERS scale. The effectiveness and economy of sunitinib ，sorafenib and pezoparib in the treatment of mRCC were compared qualitatively after the relevant data were extracted. RESULTS ：A total of 10 literatures were included ，and the total coincidence rates of 7 literatures over 75.00％. Among the 4 literature studies of sulatinib vs. sorafenib ，3 literature studies pointed out that sulatinib was the absolute advantage scheme ，and 1 literature study pointed out that sorafenib was more economical ； among the 6 literature studies of sunitinib vs. pezoparib ，4 literature studies indicated that pezoparib was the absolute advantage scheme，and 2 literature studies indicated that sunitinib was more economical. CONCLUSIONS ：In most cases ，the efficacy and economy of pezoparib in the treatment of mRCC is better than sunitinib and sorafenib ，but real world data shows that sunitinib is more economical.
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A 64-year-old man was treated with sunitinib as a first-line therapy for metastatic renal cell carcinoma. He was given oral sunitinib in cycles of 50 mg once daily for 2 weeks followed by a week off. During the 5th week of treatment right upper quadrant pain developed, but this resolved spontaneously during the 6th week (off treatment). However, on the 8th week of treatment, he was admitted to hospital because the acute right upper quadrant pain recurred with nausea, vomiting, and fever. Acute acalculous cholecystitis was then diagnosed by ultrasonography and CT. In addition, his laboratory findings indicated disseminated intravascular coagulation. Accordingly, sunitinib therapy was discontinued and broad-spectrum antibiotics initiated. He subsequently recovered after emergent percutaneous cholecystostomy. His Naranjo Adverse Drug Reaction Probability Scale score was 7, indicaing a probable association of the event with sunitinib. Suspicion of sunitinib-related acute cholecystitis is required, because, although uncommon, it can be life-threatening.
Subject(s)
Humans , Middle Aged , Acalculous Cholecystitis , Anti-Bacterial Agents , Carcinoma, Renal Cell , Cholecystitis, Acute , Cholecystostomy , Disseminated Intravascular Coagulation , Drug-Related Side Effects and Adverse Reactions , Fever , Nausea , Ultrasonography , VomitingABSTRACT
Introducción El cáncer renal representa 2,4% de los casos diagnosticados de cáncer en la población general, es más común en hombres que en mujeres, y se presenta con más frecuencia entre la 6ta y la 8ta décadas de vida. Se estima que el 16% de los pacientes se diagnostican como enfermedad metastásica. Objetivo Se presenta el caso de un paciente cuyo diagnóstico de carcinoma renal se confundió inicialmente con un tumor benigno. Métodos A un hombre de 56 años de edad se le realizó hace 3 años ese diagnóstico en un estadio avanzado de la enfermedad, a pesar del hallazgo incidental de una masa, que se consideró benigna durante 5 años. Resultados Al momento del diagnóstico de carcinoma de células claras, el tumor era Estadio IV, con metástasis a pulmón. Recibió primera línea de tratamiento con sunitinib, pero fue suspendido por toxicidad; segunda línea con pazopanib durante 1 año, después presentó progresión de la enfermedad, por lo cual se cambió a tratamiento con axitinib con respuesta parcial, sin embargo, se suspendió por toxicidad cardiaca, entre otras. Al momento el paciente ha recibido 5 ciclos de bevacizumab con adecuada tolerancia. Conclusiones Es necesario resaltar la indicación de diagnóstico adecuado y manejo quirúrgico en masas renales sospechosas.
Introduction Kidney cancer represents 2.4% of diagnosed cases of cancer in the general population; it is more common in men than in women, and occurs more frequently between the 6th and 8th decades of life. It is estimated that 16% of patients are diagnosed as metastatic disease. Objective To report the case of a male patient whose diagnosis of renal carcinoma was initially misdiagnosed as a benign tumor. Methods We present a 56-year-old male diagnosed three years back with malignancy at an advanced stage of the disease, despite the incidental finding of a tumor that for 5 years was considered benign. Results At the time of diagnosis of clear cell carcinoma, the tumor was Stage IV, with lung metastasis. He received first line treatment with sunitinib, which was discontinued due to toxicity. Subsequently, a second line with pazotinib for 1 year, then presented progression of the disease, so treatment was changed to axitinib with partial response., It was discontinued, however, due to cardiac toxicity, among others. At the time of writing, the patient has received 5 cycles of bevacizumab with adequate tolerance. Conclusions It is necessary to highlight the need for adequate diagnosis and surgical management in suspicious renal masses.
Subject(s)
Humans , Male , Middle Aged , Carcinoma, Renal Cell , Bevacizumab , Axitinib , Neoplasm Metastasis , Grief , Incidental Findings , Sunitinib , Kidney , NeoplasmsABSTRACT
ObjectiveTo investigate the clinical effect of the targeted drug sunitinib in the treatment of advanced hepatocellular carcinoma (HCC). MethodsA total of 48 patients with advanced HCC who were admitted to Chang′an Hospital form September 2015 to September 2016 were enrolled and divided into control group and observation group, with 24 patients in each group. The patients in the control group were given oral sorafenib, and those in the observation group were given oral sunitinib. The patients were followed up for 1 year, and the clinical outcome, improvement in clinical symptoms, and adverse events were recorded. The t-test was used for comparison of continuous data between groups, and the Mann-Whitney U test was used for comparison of categorical data between groups. ResultsThe disease control rate (DCR) in the observation group was 68.42% (13/19), and among these 13 patients, 4 achieved effective remission and 9 had stable disease; the DCR in the control group was 76.19%, and there was no significant difference in DCR between the two groups (P＞0.05). There was a significant difference in the incidence rate of hand-foot skin reaction between the observation group and the control group (0% vs 12.5%, U=31.07, P＜0.05). The observation group had a significantly higher incidence rate of neutropenia than the control group (25% vs 16.67%, U=29.87, P＜0.05). Both groups experienced digestive tract reactions (nausea and vomiting) and abnormal liver function; since the digestive tract reactions were tolerable, no special treatment was given, and the patients with abnormal liver function were given liver-protecting drugs, so all adverse events were effectively alleviated. ConclusionSunitinib has a good clinical effect in the treatment of advanced HCC, and further studies with a larger sample size are needed to investigate the long-term clinical effect of sunitinib and combined treatment.
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BACKGROUND: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. METHODS: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. RESULTS: The median follow-up was 16.4 months (interquartile range, 8.3–31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. CONCLUSION: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.
Subject(s)
Humans , Body Mass Index , Carcinoma, Renal Cell , Follow-Up Studies , Incidence , Liver , Neoplasm Metastasis , Proportional Hazards Models , Retrospective Studies , Survival RateABSTRACT
Objective : To evaluate the clinical usefulness of gargling with hangeshashinto (HST) for treatment of oral mucositis (OM) caused by sunitinib in patients with metastatic renal cancer. Patients and methods : The study included 22 patients with sunitinib-induced OM. Among them, 12 patients were instructed to gargle with 2.5 g of HST for 30 seconds after each meal, 3 times a day, and to refrain from eating and drinking afterward (gargling group). The remaining 10 patients were treated without gargling (non-gargling group). The changes in the following outcome measures after treatment were analyzed and compared between the two groups : the Karnofsky Performance Status (KPS), OM grade, body weight, albumin (Alb) levels, hemoglobin (Hb) levels, and eating status. Results : In the non-gargling group, the OM grade and eating status were not well improved, and KPS, body weight, Alb and Hb levels decreased. In the gargling group, despite a decrease in KPS, both OM grade and eating status improved from the day after the start of gargling, while no significant decreases were observed in body weight, Alb levels, or Hb levels after treatment. The gargling group showed better responses in all measures than the non-gargling group. Discussion : OM associated with cancer chemotherapy interferes with treatment completion. HST is a typical Kampo medicine belonging to the shashinto group, gargling with HST is also effective for treating OM. It appears that gargling with HST improves earlier stage of OM and eating status, thereby suppressing a decrease in KPS, body weight, Alb, and Hb levels.
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Objective@#To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival.@*Methods@#The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients′ overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models.@*Results@#The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS.@*Conclusions@#The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.
ABSTRACT
Objective To investigate the therapeutic effects of presurgical TMT on the heights and levels of inferior vena cava(IVC)thrombi,and to assess its impact on surgical strategy.Methods We retrospectively reviewed data of 18 patients with renal cell carcinoma(RCC)involving IVC tumor thrombi who were treated at our hospital with presurgical TMT followed by an IVC thrombectomy.Data from 18 patients(16 men and 2 women)were included in the analysis.The median age was 53.5 years(range:33-75 years),and the mean BMI was 24.7kg/m2(rrange:18.1 -30.4 kg/m2).4 cases of tumors located in the left kidney,14 cases were right.The changes in heights and levels of the IVC thrombi were compared using computed tomography or magnetic resonance imaging.The IVC tumor thrombus level was evaluated according to the Mayo classification.Results The tumor thrombus levels before TMT were stage Ⅰ in 1 patient,Ⅱ in 1 2 patients,Ⅲ in 4 patients,and Ⅳ in 1 patient.The presurgical TMT was sorafenib in 6 patients(33.3%),sunitinib in 9(50.0%),and axitinib in 3(16.7%).After a median of 2 treatment cycles(range:1-6 cycles),three patients experienced grade 3 adverse events.One patient stopped treatment after 6 weeks owing to intolerable skin reactions and difficulty walking.The tumor thrombus height decreased measurably in 11 patients(61.1%).The thrombus height remained stable in 5 patients(27.8%)and was enlarged in 2(11.1%).The median reduction of tumor thrombus height was -0.53 cm (range:-4.23 to 1.21 cm).The median change in the maximum diameter of the thrombus was -0.30 cm (range:-1.23 to 0.29 cm).Down-staging of the thrombus level occurred in 4 patients(22.2%);the surgical strategy was modified in 3 patients(level≥Ⅲ)to avoid cardiopulmonary bypass and complicated liver mobilization under robot-assisted laparoscopy.Conclusions Our data suggest a limited influence of presurgical TMT,with a positive benefit in RCC patients with level Ⅲ and Ⅳ thrombus.Thrombus-level regression may potentially alter the surgical strategy,especially robotic surgery.Additionally,preoperative targeted therapy did not significantly increase perioperative mortality and risk of serious complications.
ABSTRACT
OBJECTIVE:To evaluate the affordability of 3 anti-tumor targeted drugs gefitinib,trastuzumab and sunitinib in ur-ban and rural residents of Hubei province,and to provide reference for medical insurance price admission of anti-malignant tumor targeted drugs in China. METHODS:Referring to the incidence of malignant tumor stated in statistical yearbook of Hubei province and income data of urban and rural residents in Hubei province,based on the policy of reducing the price of imported drugs by 50% mentioned in the national drug price negotiations,and assume the drugs are included in the medical insurance reimbursement list,WHO/HAI standard survey method,catastrophic expenditure evaluation method and poverty effect evaluation method were ad-opted to calculate the affordability of 3 drugs. RESULTS:According to WHO/HAI standard survey method,increment of payment for 3 drugs were 64.00%-74.00% before and after 50% discount and reimbursement. According to catastrophic expenditure evalua-tion method,50% discount of gefitinib and reimbursement gefitinib,trastuzumab and sunitinib in urban area would result in cata-strophic expenditures of 20.00%、59.28% and 35.48% patients;in rural area,would result in catastrophic expenditures of 50.63%、74.72% and 75.93% patients. According to poverty effect evaluation method,50% discount of 3 drugs and reimbursement caused less than 31.95% urban and rural patients falling to poverty. CONCLUSIONS:Fifty percentage discount of 3 anti-tumor targeted drugs mentioned in the national drug price negotiations cause the economic burden more serious for rural residents than urban resi-dents. In the formulation of policies,the corresponding reimbursement ratio should be adjusted according to urban and rural areas, drug price and disease types for a balance of patients with different economic burden.