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OBJECTIVE To evaluate the cost-effectiveness of regorafenib in the treatment of hepatocellular carcinoma after failure of sorafenib from the perspective of Chinese health system. METHODS Based on a phase Ⅲ trial（RESORCE）， the partition survival model （PSM） and Markov model were constructed. The cycle was set as four weeks， the duration of the study lasted for lifetime， the annual discount rate was 5%. Drug cost data was obtained from yaozhi.com， other cost data were obtained from Anhui Provincial Medical Insurance Bureau and related literature， and utility values were obtained from literature. The incremental cost-effectiveness ratio （ICER） was used as the evaluation index， and the value of willingness to pay （WTP） was three times of China’s gross domestic product （GDP） per capita in 2022； one-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The incremental cost of regorafenib group versus placebo group in PSM and Markov model was 112 116.95 yuan and 96 617.19 yuan， respectively. The incremental effectiveness was 0.31 QALYs and 0.32 QALYs， respectively. The ICERs were 360 751.01 yuan/QALY and 301 114.45 yuan/QALY， which were both greater than the value of WTP； regorafenib was not cost-effective. Results of one-way sensitivity analysis showed that the utility of progression-free survival and progressive disease， the unit cost of regorafenib had the greatest influence on the results， but ICER was always greater than the WTP within the floating range of each parameter. Under the WTP of 3 times China’s per capita GDP in 2022， the probabilities of regorafenib with cost-effectiveness were 0.8% （PSM） and 11.4% （Markov）. CONCLUSIONS Under the WTP of 3 times the per capita GDP of China， regorafenib is not cost-effective in the treatment of hepatocellular carcinoma after failure of sorafenib treatment， compared with placebo.
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Objective: To investigate the therapeutic effect and mechanism of lenvatinib on regorafenib-resistant hepatocellular carcinoma cells. Methods: CCK-8 and clone formation assay were used to observe the inhibitory effect of lenvatinib on the growth of hepatocellular carcinoma cells. Flow cytometry was used to detect the apoptosis of regorafenib-resistant hepatocellular carcinoma cells treated with lenvatinib. The expression levels of related proteins were detected by western blot and immunohistochemical staining. The inhibitory effect of lenvatinib on the tumor formation ability of regorafenib-resistant hepatocellular carcinoma cells in vivo was observed by subcutaneous tumor formation experiment in mice. Results: CCK-8 and clone formation assay showed that lenvatinib could inhibit the proliferation of regorafenib-resistant hepatocellular carcinoma cells. The number of clones of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group (120.67±11.06, 53.00±11.14, 55.00±9.54, 78.67±14.64) were all lower than those in control group (478.00±24.52, 566.00±27.87, 333.67±7.02, 210.00±12.77, all P<0.05). Flow cytometry showed that lenvatinib could promote apoptosis of regorafenib-resistant hepatocellular carcinoma cells, the apoptosis rates of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group [(12.30±0.70)%, (9.83±0.38)%, (15.90±1.32)%, (10.60±0.00)%] were all higher than those in control group [(7.50±0.87)%, (5.00±1.21)%, (8.10±1.61)%, (7.05±0.78)%, all P<0.05]. The apoptosis-related protein levels suggested that apoptosis was increased in the treatment of lenvatinib. The animal study showed that lenvatinib can inhibit the growth of regorafenib-resistant cells in vivo. Immunohistochemistry and western blot results showed that lenvatinib could down-regulate the abnormally activated IGF1R/Mek/Erk signaling pathway in regorafenib-resistant cells. Conclusion: Lenvatinib can reverse regorafenib resistance in hepatocellular carcinoma, possibly by down-regulating IGF1R/Mek/Erk signaling pathway.
Subject(s)
Animals , Mice , Humans , Apoptosis , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Liver Neoplasms/pathology , Signal TransductionABSTRACT
Objective:To explore the efficacy and influencing factors of irinotecan-loaded CalliSpheres drug-eluting bead-transcatheter arterial chemoembolization (DEBIRI-TACE) combined with regorafenib in the third-line or above treatment of unresectable colorectal cancer liver metastases.Methods:From June 2018 to June 2020, 53 patients with unresectable colorectal cancer liver metastases admitted to Linyi Cancer Hospital of Shandong Province who had failed at least second-line systemic chemotherapy were retrospectively analyzed. The patients were divided into observation group (24 cases) and control group (29 cases) according to different treatment regimes. The control group only received regorafenib monotherapy, and the observation group received regorafenib combined with DEBIRI-TACE. According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate (ORR) and disease control rate (DCR) were evaluated, and the progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. The Cox proportional hazards model was used to analyze the OS influencing factors in the observation group. The treatment related adverse reactions were observed.Results:After 2 months of treatment, the ORR of the observation group was 75.0% (18/24) , and the DCR was 91.7% (22/24) , both were higher than those of the control group [6.9% (2/29) and 51.7% (15/29) respectively], with statistically significant differences ( χ2=25.92, P<0.001; χ2=9.94, P=0.002) . There were no statistically significant differences in the incidences of regorafenib-related adverse reactions such as hand-foot skin reaction [62.5% (15/24) vs. 65.5% (19/29) , χ2=0.05, P=0.819], fatigue [41.7% (10/24) vs. 44.8% (13/29) , χ2=0.05, P=0.817], hypertension [29.2% (7/24) vs. 34.5% (10/29) , χ2=0.17, P=0.679], diarrhea [25.0% (6/24) vs. 27.6% (8/29) , χ2=0.04, P=0.832], hoarseness [16.7% (4/24) vs. 17.2% (5/29) , χ2=0.01, P=0.956] and proteinuria [8.3% (2/24) vs. 10.3% (3/29) , χ2=0.06, P=0.803] between the two groups. The main adverse reactions related to DEBIRI-TACE in the observation group were fever, pain, nausea and vomiting, etc., which were relieved after symptomatic treatment. No serious complications such as ectopic embolism of CalliSpheres drug eluting bead occurred. By the end of the follow-up, among the 24 patients in the observation group, the median OS of patients with simultaneous liver metastases was 12 months, and that of patients with metachronous liver metastases was 22 months, with a statistically significant difference ( χ2=4.29, P=0.026) . The median OS of patients with 3-5 liver metastases was 21 months, and that of patients with more than 5 liver metastases was 14 months, with a statistically significant difference ( χ2=3.35, P=0.040) . The median OS of Child-Pugh grade A patients was 22 months, and that of Child-Pugh grade B patients was 13 months, with a statistically significant difference ( χ2=4.22, P=0.027) . The median OS was 16 months in patients with extrahepatic metastases and 23 months in patients without extrahepatic metastases, with a statistically significant difference ( χ2=7.68, P=0.013) . Cox proportional hazards model analysis showed that simultaneous liver metastases ( HR=1.59, 95% CI: 1.02-2.47, P=0.031) and extrahepatic metastases ( HR=1.61, 95% CI: 1.29-2.01, P=0.020) were independent risk factors influencing OS of patients in the observation group. The median PFS of the observation group was 9 months, and that of the control group was 5 months, with a statistically significant difference ( χ2=7.78, P=0.005) . The median OS of the observation group was 17 months, and that of the control group was 11 months, with a statistically significant difference ( χ2=16.81, P<0.001) . Conclusion:DEBIRI-TACE combined with regorafenib is effective in the third-line or above treatment of unresectable colorectal cancer liver metastases, with tolerable adverse reactions. It is a safe and feasible treatment method. The prognosis of patients with simultaneous liver metastases or extrahepatic metastases is worse.
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Objective:To analyze the dosing, efficacy and safety of Regorafenib in elderly patients with metastatic colorectal cancer.Methods:Clinical data of 40 elderly patients with advanced colorectal cancer treated with regorafenib from June 2018 to October 2019 at Beijing Hospital were collected.The dosing, effectiveness and safety of regorafenib were retrospectively analyzed.The primary endpoint was overall survival(OS).Results:A total of 40 elderly patients were enrolled in this study, including 25 males and 15 females, with a median age of 66 years.The initial dose of Regorafenib was 80 mg, and the maintenance dose was 80 mg in 14(35.0%)patients, 120 mg in 20(50.0%)patients and 160 mg in 6(15.0%)patients.Thirty-one patients were treated with Regorafenib and 9 patients were given a combination therapy including Regorafenib.The objective response rate(ORR)was 2.5%(1 case), and the disease control rate(DCR)was 45.0%(18 cases). The median progression free survival(PFS)was 2.2 months(95% CI: 2.1-4.0)and the median OS was 8.8 months(95% CI: 7.1-11.2). There was no significant difference in PFS or OS in different maintenance dose groups( P<0.05). Patients who received 120 mg Regorafenib as a maintenance dose showed longest survival with a median OS of 9.8 months(95% CI: 6.9-14.0). There was no difference in median OS between the Regorafenib group and the combination therapy group( χ2=0.1, P>0.05). Grade 3 and 4 adverse reactions occurred in 11 patients(27.5%). Common adverse reactions were hand-foot skin reaction, fatigue, hypertension, diarrhea, elevated transaminase levels and proteinuria. Conclusions:Regorafenib offers a good survival benefit for elderly patients with advanced colorectal cancer who failed to respond to standard therapy.The dosing strategy, starting with a low dose of Regorafenib and escalating gradually as tolerance builds up, is recommended for elderly patients, when both efficacy and safety are considered.The proportion of patients who can tolerate 120 mg Regorafenib as a maintenance dose is high with relatively long overall survival, indicating it is appropriate for the elderly.
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This study investigated the mechanism underlying the suppression of estrogen receptor-positive MCF-7 cell growth by regorafenib. MCF-7 cells were treated with regorafenib, and the effect of regorafenib on multiple cancer-associated pathways was evaluated. Although regorafenib effectively inhibited the proliferation of MCF-7 cells, it had no effect on the proliferation of the normal breast epithelial cell line MCF10A. Regorafenib suppressed MCF-7 cell migration, probably by regulating the homeostatic expression of matrix metalloproteinases and the tissue inhibitor of MMPs. Furthermore, it upregulated p21 expression, downregulated cyclin B1 and cyclin D1 expresssions, and caused cell cycle arrest. In addition, regorafenib induced apoptosis in MCF-7 cells by reducing Mcl-1 expression and activating caspase signaling. These results demonstrate that regorafenib has the potential to be an effective drug for treating breast cancer
Subject(s)
Cell Cycle/immunology , MCF-7 Cells/classification , Breast Neoplasms/pathology , Pharmaceutical Preparations , Receptors, Estrogen , Apoptosis , Cyclin D1/pharmacology , Epithelial Cells/classification , Cyclin B1/pharmacologyABSTRACT
As the first-line drug for the treatment of primary liver cancer, sorafenib has been widely used in clinical practice, but its drug resistance and toxic and side effects have become increasingly apparent, along with limited efficacy. In recent years, the research on regorafenib for the treatment of hepatocellular carcinoma (HCC) has gradually become a hotspot. The RESORCE trial has shown that regorafenib can significantly extend the overall survival time of patients with failed sorafenib treatment to 10.6 months, and regorafenib was approved as a second-line drug for advanced HCC by Food and Drug Administration in 2017. This article reviews the molecular mechanism, efficacy evaluation, combination therapy, and criteria for patient selection in the treatment of HCC with regorafenib, so as to provide a direction for further research in the future.
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Hepatocellular carcinoma (HCC) is the world's fifth common malignant tumor,ranks as the second and sixth leading causes of cancer death in nale and female.In a majority of the cases,HCC is diagnosed in advanced stage of disease when curative treatment options are not applicable.In 2007,sorafenib was approved for the first-line treatment of advanced HCC.Targeted therapy,which could improve the overall survival and qualities of life,brought a new hope for patients with advanced HCC.Unfortunately,in the past 10 years,various drugs tested in numerous different trials failed to denonstrate any benefit.Recent studies have demonstrated the efficacy of two molecular targeted agents,the second-line agent regorafenib and the first-line agent lenvatinib.Furthermore,preliminary results of immune checkpoint inhibitors such as anti-PD-1/PD-L1 or CTLA-4 antibodies were quite encouraging.These new drugs brought dawn of targeted therapy of HCC.
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This study was designed to investigate the inhibitory effects of regorafenib (REG) on the catalytic activities of 12 kinds of human UGT isoforms and human liver microsomes (HLM) in vitro. The broader potential of REG to perpetrate drug-drug interactions (DDI) arising from UGT enzyme inhibition is predicted by in vitro-vivo extrapolation (IV-IVE). Fifty mixed HLM and 12 kinds of recombinant UGTs were utilized as enzyme sources to evaluation the inhibitory effects of REG against UGTs. 4-Methylumbelliferone (4-MU) as a nonselective substrate of UGTs except for UGT1A4, N-(3-carboxypropyl)-4-hydroxy-1,8-napht-halimide (NCHN) and N-butyl-4-(4-hydroxyphenyl)-1,8-naphthalimide (NPHN) as the specific fluorescent substrate of UGT1A1, and trifluoperazine (TFP) as the specific substrate of UGT1A4. The half maximal inhibitory concentration (IC50) was calculated via the nonlinear regression analysis using Graphpad Prism 6.0, the inhibition kinetic types were selected and evaluated based on the intersection location of Lineweaver-Burk plot and Dixon plot, and Ki values were determined by the second plot of slopes. The potential DDI risk based on UGT1A1 inhibition was also evaluated through the in vitro parameters. The results demonstrated that REG displayed strong inhibitory effects against UGT1A1, 1A7, 1A9, and 2B7. The IC50 values were from 0.15 to 6.6 μmol·L-1 and Ki values from 0.027 to 14 μmol·L-1. The REG exerted competitive inhibition against UGT1A1-mediated 4-MU-O-glucuronidation and UGT1A1-mediated NPHN-O-glucuronidation, while the inhibition of NCHN-4-O-glucuronide by REG was suited to noncompetitive inhibition in both HLM and recombinant UGT1A1. Likewise, REG exhibited a mixed efficacy in inhibition of UGT1A7-, UGT1A9-, and UGT2B7-catalyzed 4-MU-O-glucuronidation. The AUC ratio of UGT1A1 specific substrates NPHN and NCHN can be increased by 101% to 302% and 13% to 109%, respectively. These results suggest that much caution should be exercised when REG is co-administered with UGT1A1 substrates.
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PURPOSE: The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients. MATERIALS AND METHODS: Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on/1 week off). RESULTS: None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a hand-foot skin reaction (n=31). CONCLUSION: This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.
Subject(s)
Humans , Appointments and Schedules , Disease-Free Survival , Follow-Up Studies , Gastrointestinal Stromal Tumors , Imatinib Mesylate , SkinABSTRACT
Objective: To establish an LC-MS/MS method for the determination of 4-( 4-amino-3-fluorophenoxy )-N-methylpyri-dine-2-carboxamide ( AFP-PMA) as a genotoxic impurity in regorafenib. Methods: The content of AFP-PMA was determined by an LC-MS/MS method. A Waters XBridge Shield RP18 column was adopted to separate the samples and the column temperature was 50℃. The mobile phase consisted of 5 mmol·L-1ammonium acetate aqueous (A)-acetonitrile (B) with gradient elution (0~9 min, 5%B→90%B) at a flow rate of 1. 0 ml·min-1. An electrospray ionization source (ESI) was used in a positive-ion and multiple reactions monitoring mode. The ion channel was m/z 262. 2→244. 1. Results:The standard curve was linear within the range of 2. 41-980. 90 ng·ml-1(r=0. 9998) and the limit of quantification was 8. 02 ng·ml-1. The limit of detection was 2. 41 ng·ml-1, which was e-quivalent to 0.000241% for the concentration of regorafenib. The average recovery was 100.95% and RSD was 2.37% (n=9). Conclusion:The method has good specificity, promising accuracy and high sensitivity, which can be used for determining the trace genotoxic impurity AFP-PMA in regorafenib.
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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.
Subject(s)
Humans , Asian People , China , Consensus , Diagnosis , Gastrointestinal Stromal Tumors , Gastrointestinal Tract , Imatinib Mesylate , Korea , Medical OncologyABSTRACT
Objective:To optimize the formula of regorafenib solid dispersion .Methods: On the basis of preliminary studies on the carrier and drug/carrier ratio, an orthogonal test was used to study the formula of regorafenib solid dispersion .The orthogonal table of L9 (34 ) was designed to study the drug/carrier ratio, ultrasound time and bath temperature .Results: Regorafenib solid dispersion was prepared by a solvent method with polyvinylpyrrolidone K 30 as the carrier.The drug/carrier ratio was 1 ∶7, the ultrasound time was 4min, and the bath temperature was 30℃.Regorafenib solid dispersion showed good stability confirmed by differential scanning calorimetry and X-ray diffraction .The dissolution in 30 min reached above 90 %.Conclusion: The preparation process is stable and reproducible , which can be used to prepare regorafenib solid dispersion .
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OBJECTIVE:To establish a method for the determination of related substances in regorafenib. METHODS:Gradi-ent elution HPLC was performed on the column of Waters Atlantis T3 C18 with mobile phase A of 0.1%Trifluoroacetic acid solution and B of acetonitrile(gradient elution)at a flow rate of 1.0 ml/min,the detection wavelength was 232 nm and column temperature was 35 ℃,injection volume was 10 μl. RESULTS:AFP-PMA urease(impurity A),FP- dimethyl pyridine carboxamide(impurity B),3,4-bis-CTF-aminoformamido-PMA(impurity C),regorafenib and other impurities were well separated;the linear range was 0.511-5.108 μg/ml for impurity A(r=0.999 9),0.287-2.869 μg/ml for impurity B(r=0.999 5),0.360-3.604 μg/ml for impurity C (r=0.999 9)and 1.444-14.442 μg/ml for regorafenib(r=0.999 8);the detection limit were 0.052,0.022,0.084 and 0.071 μg/ml, respectively;RSDs of precision,stability and reproducibility tests were lower than 3%;recoveries of impurity A,B and C were 102.7%-106.3%(RSD=1.09%,n=9),98.2%-102.9%(RSD=1.83%,n=9)and 98.6%-104.3%(RSD=1.57%,n=9). CON-CLUSIONS:The method is sensitive,rapid,accurate and reliable,and can be used for the determination of related substances in regorafenib.
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Regorafenib is a novel oral multitargeted tyrosine kinase inhibitor having both antitumor and anti‑angiogenic activities. Regorafenib was recently approved by US Food and Drug Administration in February 25, 2013 in the treatment for patients with advanced gastrointestinal stromal tumor and for the treatment of patients with metastatic colorectal carcinoma after disease progression or intolerance to imatinib mesylate and sunitinib therapy. Oral regorafenib demonstrates a high level of efficacy with acceptable tolerability with the 160 mg daily for 3 weeks followed by 1 week off schedule; a continuous schedule could be of interest. Hypertension, mucositis, hand foot skin reaction, diarrhea and asthenia are the most common side‑effects. Regardless of these encouraging results, studies investigating, adjuvant and neoadjuvant settings are awaited, as well as trials using regorafenib in combination with chemotherapy or other targeted therapies. Clinical trials investigating regorafenib in other tumor types are ongoing.
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PURPOSE: Regorafenib, an oral multi-targeted tyrosine kinase inhibitor, is considered the new standard of care in patients with chemotherapy-refractory colorectal cancers (CRCs). However, there are no data on this drug in Korean patients. MATERIALS AND METHODS: We evaluated patients who received oral regorafenib 160 mg once daily during the first 3 weeks of each 4-week cycle between August 2013 and September 2013. All patients had previously progressed fluorouracil, irinotecan, and oxaliplatin with or without biologic agents such as cetuximab or bevacizumab. RESULTS: Thirty-two patients were enrolled (median age, 57 years; male:female ratio, 20:12; Eastern Cooperative Oncology Group performance status [0-1:2], 31:1; colon:rectum, 21:11). The overall response rate was 3.1% and the disease control rate was 50.0% (95% confidence interval [CI]) with one partial response and 15 patients with stable disease. The median progression-free survival was 4.2 months (95% CI, 3.1 to 5.2 months) and the median overall survival has not yet been reached. The most common adverse events of grade two or higher related to regorafenib were hand-foot skin reaction (25%), mucositis (19%), abdominal pain (9%), and liver function test (LFT) abnormalities (9%). Grade 3 or 4 toxicities included LFT abnormalities (9%), abdominal pain (9%), rash (6%), anemia (3%), leukopenia (3%), neutropenic fever (3%), and fatigue (3%). There was no treatment-related death. CONCLUSION: Regorafenib appears to have promising activity and tolerable toxicity profiles in Korean patients with refractory CRC, consistent with the CORRECT trial findings.
Subject(s)
Humans , Abdominal Pain , Anemia , Biological Factors , Colorectal Neoplasms , Disease-Free Survival , Exanthema , Fatigue , Fever , Fluorouracil , Korea , Leukopenia , Liver Function Tests , Mucositis , Protein-Tyrosine Kinases , Skin , Standard of CareABSTRACT
Angiogenesis plays a vital role in carcinogenesis and development of colorectal cancer. Treatment targeting VEGF signaling pathway acquires important survival prolong for advanced colorectal cancer patients. For advanced colorectal cancer patients,bevacizumab could furtherly prolongs survival time in the setting of first line,second line and continuing therapy after first-progression therapy combined with chemothe-rapy. Aflibercept used in combination with irinotecan-containing regimen improves the survival of advanced colorectal cancer patients in second-line setting. Regorafenib also improves the survival of advanced colorectal cancer patients who have progressed after all line treatment. Considering these suivival benefit and their favora-ble safety,anti-angiogenic agents should be taken into all lines of therapy in the management of advanced colo-rectal cancer.
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Gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, have represented an important advance in oncology field with the success of molecular targeted therapy. Since the approval of the tyrosine kinase inhibitor (imatinib) in 2002, the survival of patients with advanced GISTs has significantly increased. Accurate histopathologic diagnosis of GISTs and multidisciplinary approach has become more important for successful management of GISTs. Recently, imatinib has become a standard treatment even in adjuvant setting, and regorafenib has been approved for advanced GIST after failure of imatinib and sunitinib. This review presents here the updated results of relevant clinical studies for the further revision to the guideline of Korean GIST study group. We hope this review will help enhance the quality of diagnosis, treatment, and care of patients with GIST in Korea.
Subject(s)
Humans , Benzamides , Gastrointestinal Stromal Tumors , Gastrointestinal Tract , Indoles , Korea , Molecular Targeted Therapy , Phenylurea Compounds , Piperazines , Protein-Tyrosine Kinases , Pyridines , Pyrimidines , Pyrroles , Imatinib MesylateABSTRACT
Gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, have represented an important advance in oncology field with the success of molecular targeted therapy. Since the approval of the tyrosine kinase inhibitor (imatinib) in 2002, the survival of patients with advanced GISTs has significantly increased. Accurate histopathologic diagnosis of GISTs and multidisciplinary approach has become more important for successful management of GISTs. Recently, imatinib has become a standard treatment even in adjuvant setting, and regorafenib has been approved for advanced GIST after failure of imatinib and sunitinib. This review presents here the updated results of relevant clinical studies for the further revision to the guideline of Korean GIST study group. We hope this review will help enhance the quality of diagnosis, treatment, and care of patients with GIST in Korea.