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Being the most common solid malignant tumor in the digestive system and the third leading cause of cancer-related death worldwide， hepatocellular carcinoma （HCC） is characterized by insidious onset， early recurrence/metastasis and poor prognosis. With the advantages of targeted precision， high specificity， minimal drug resistance， remarkable therapeutic efficacy and fewer side effects， molecular targeted drugs have become the hotspot and focus of tumor therapy research in recent years. As more is learned about the mechanism and clinical efficacy， some molecular targeted drugs have been recommended by HCC treatment guidelines. This paper reviewed the mechanism of HCC targeted therapy， molecular targeted drugs， relevant therapeutic protocols and outcomes so as to provide reference and evidence for subsequent research.
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Genodermatoses are a relatively independent type of skin diseases, with early onset, complex clinical manifestations and multiple system involvement. Current treatments of genodermatoses are still limited with poor therapeutic effect, and the quality of life of patients is greatly affected. This review summarizes prospective treatment methods of some hereditary skin diseases and related research progress, including innovative application of traditional medicines, biologics and small-molecule targeted drugs, stem cell therapy and gene editing, aiming to provide more reference for clinicians.
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In recent years, with the emergence of new research evidence, the domestic and foreign guidelines in the field of gastrointestinal stromal tumors (GISTs) have been updated. The adjusted contents cover almost every link of GISTs management, from GISTs diagnosis, biological behavior, surgical treatment to targeted drug treatment. Since 2020, the NCCN of the United States has separated the contents related to GISTs from the clinical practice guide for soft tissue sarcoma for the first time to form 2021 V.1 versions. The CSCO has also adjusted and upgraded the previous consensus of Chinese experts on the diagnosis and treatment of GISTs to 2020 and 2021 versions of the guidelines for the diagnosis and treatment of GISTs. This opens a new model of accurate diagnosis and treatment of GISTs under the guidance of evidence-based medicine. The listing of new targeted drugs afatinib and ripretinib is expected to get rid of the drug-resistant treatment dilemma of metastatic GISTs, enrich the back-line treatment camp, provide more opportunities for surgical intervention, and then bring survival benefits to patients with advanced GISTs.
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Since sorafenib has been first-line molecular-targeted drug for advanced hepatocellular carcinoma (HCC), clinical studies in the last 10 years failed to confirm that a new molecular-targeted drug or immune checkpoint inhibitor was superior or non-inferior to sorafenib, or approved second-line treatment for patients with the failure of sorafenib. However, many clinical studies published in 2017 have changed people′s previous understanding. REFLECT trial showed that as the first-line treatment of advanced HCC, lenvatinib was non-inferior than sorafenib. In addition, RESORCE trial and CheckMate-040 trial confirmed respectively that regorafenib and PD-1 inhibitor nivolumab were options of second-line treatment for patients with advanced HCC after sorafenib treatment. The development of these drugs will bring a new prospect for advanced HCC patients.
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Larotrectinib (also called LOxO-101, ARRY-470, and VITRAKVI?) is a kind of new high selective and broad-spectrum small molecule that is administered orally. Larotrectinib is tropomyosin receptor kinase (TRK) inhibitor and is used in the treatment of neuro-trophin tyrosine kinase receptor (NTRK) gene fusion in children and in adults. Based on use of larotrectinib against solid tumor in a vari-ety of NTRK gene fusion, larotrectinib has a good curative effect and security. On November 27, 2018, the drug was approved by the Food and Drug Administration (FDA) for the first time in the world. It is used in the treatment of no unknown drug resistant mutations, a broader shift, or partial surgical treatment, and after the treatment of disease progress of NTRK gene fusion in children and adult pa-tients with solid tumor. This article reviews the latest research progress in the research background, structure, and mechanism of ac-tion, clinical trials, adverse reactions and treatment, and drug resistance mechanism of larotrectinib.
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Microvascular invasion (MVI) is one of the invasive characteristics of hepatocellular carcinoma (HCC) and also an independent risk factor for intrahepatic and distant metastasis of hepatocellular carcinoma.The occurrence of MVI in patients with hepatocellular carcinoma is universal and can occur in different stages of hepatocellular carcinoma,which is the result of the joint action of multiple factors,including tumor diameter,tumor morphology,tumor pathological grading,and hepatitis B virus activity and replication.For patients with preoperative assessment of MVI risk factors,reasonable surgical plans should be made according to the basic conditions of patients.Non-anatomic hepatectomy is performed to expand the resection scope as far as possible (at least ＞ 1 cm),and anatomic hepatectomy is performed with complete Laennec cystectomy along the Glisson system.Pathological examination is the gold standard of MVI diagnosis,and standardized diagnosis can improve the detection rate of MVI.MVI is mainly related to early postoperative recurrence of hepatocellular carcinoma (within 1 year).For patients with positive MVI after HCC resection,selective combination with transcatheter arterial chemoembolization,radiotherapy and molecular targeted drugs can reduce tumor recurrence and prolong the survival time of patients with liver cancer without recurrence.Therefore,MVI has important clinical significance for the comprehensive diagnosis and treatment of hepatocellular carcinoma.
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Objective To evaluate the efficacy and safety of sunitinib versus sorafenib in the first-line treatment of advanced renal cell carcinoma.Methods Forty-two patients with advanced renal cell carcinoma were divided into two groups according to the therapeutic method.Twenty patients were treated with sunitinib (50 mg, oral administration, once a day, for 4 weeks, drug withdrawal of 2 weeks, 6 weeks was a cycle) and 22 patients were treated with sorafenib (400 mg, oral administration, twice a day, until the disease progression, 6 weeks was a cycle).The efficacy and toxicity were evaluated every 2-cycle treatment.Results All 42 patients could be evaluated.The disease remission rate (RR), disease control rate (DCR) of sunitinib group and sorafenib group were 30.0％ (6/20), 22.7％ (5/22), 90.0％ (18/20), 77.3％ (17/22) respectively,the median progression free survival (PFS) were 10.8, 6.2 months, the median overall survival (OS) were 25.6, 18.6 months respectively.There were no statistical differences in the RR (x2 =0.287, P =0.592) and DCR (x2 =1.222, P =0.269) between the two groups.There were statistical difference in the PFS (x2 =6.041, P =0.014) and OS (x2 =11.245, P =0.001) between the two groups.The most common toxicities of the sunitinib group were diarrhea, fatigue, oral mucositis, nausea, vomiting, all these toxicities were mainly Ⅰ-Ⅱ degree, and could be well tolerated.The hand-foot syndrome rate of the sorafenib group obviously exceeded the sunitinib group (59.1％ vs.25.0％ , x2 =4.972, P =0.026).Conclusion Sunitinib has good efficacy in the first-line treatment of advanced renal cell carcinoma with less toxicity than sorafenib, so it is worthy of popularization.
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Objective:To invetigate the use of targeted anticancer drugs in our hospital during 2011-2013 to provide reference for the clinical rational drug use. Methods:The utilization of anti-tumor molecular targeted drugs in our hospital during 2011-2013 was retrospectively analyzed in respect of consumption sum, DDDs and DDC. Results:The proportion of consmption sum of anti-tumor mo-lecular targeted drugs in the total consumption sum was increased year by year, and that in 2012 and 2013 was over 60%. Protease ki-nase inhibitors accounted for 41. 29%-73. 41% in the consumption sum of anti-tumor molecular targeted drugs; monoclonal antibody accounted for 19. 40%-30. 88%; the other drugs accounted for 7. 19%-27. 83%. The consumption sum and the number of receiving medication patients of rituxan and cetuximab were not synchronized well, and the patients were born the higher cost. Conclusion:The use of anti-tumor molecular targeted drugs in our hospital is increased year by year, and the oral administration of anti-tumor molecular targeted drugs is with especially wide application.
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Surgical resection and liver transplantation are still the preferred treatments for patients with hepatocellular carcinoma (HCC).For the patients with advanced HCC which are not suitable for surgical resection,traditional chemotherapy can not improve the prognosis.Molecular targeted therapy is a new method and tendency in the treatment of HCC.Multiple targets inhibitors,vascular endothelial growth factor inhibitors and monoclonal antibodies for HCC are widely researched and applied.
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The effective and toxic ranges of anticancer drugs are very narrow and, in some cases, inverted. Thus determination of the most appropriate dosage and schedule of administration is crucial for optimal chemotherapy. In common arm trials conducted in Japan and by Southwest Oncology Group (SWOG) that used the same doses and schedules for the administration of carboplatin plus paclitaxel, the frequency of hematological toxicity was significantly higher in the Japanese trials than in the SWOG trial, despite demonstrating similar response rates. The frequency of epidermal growth factor receptor (EGFR) mutations in tumors was significantly higher among East Asian populations, and these populations are also reported to demonstrate a higher response rates to epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs). The prevalence of interstitial lung disease induced by treatment with EGFR-TKIs has been shown to be quite high in the Japanese population. Clinical trials of cetuximab against non-small cell lung cancer and of bevacizumab against stomach cancer have shown that these agents are only active in Caucasians. In a trial examining the use of sorafenib after transarterial chemoembolization in Korean and Japanese patients with advanced hepatocellular carcinoma, the compliance and dose intensity of the drug were quite low compared with other trials. Although not only identified pharmacogenomics differences but also differences in social environment, and regional medical care, including pharmacoeconomics strongly influence ethnic differences in treatment response, further identification and understanding of the pharmacogenomics underlying ethnic differences will be essential to timely and reliable global development of new anticancer drugs.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Asian People , Carcinoma, Non-Small-Cell Lung/drug therapy , Chemoembolization, Therapeutic , Clinical Trials as Topic , Drug Design , Ethnicity , Japan , Lung Diseases, Interstitial/chemically induced , Lung Neoplasms/drug therapy , Mutation , Pharmacogenetics/methods , ErbB Receptors/genetics , Republic of KoreaABSTRACT
As the efficacies of chemotherapy in the treatment of advanced non-small cell lung cancer(NSCLC) have reached a plateau, the molecularly targeted therapy becomes a new method to improve curative effects.The molecular targeted drugs include epidermal growth factor receptor inhibitors, anti-angiogenesis drugs, etc.As one of the representative drugs of EGFR inhibitors, Gefitinib, has a low clinical benefit index.Erlotinib, the first EGFRTK inhibitor, can enhance the survival of patients, and may serve as a potential choice for the first-line treatment of advanced NSCLC.Bevacizumab combined with chemotherapy has shown a favorable clinical effect in the first-line treatment, and it is also the first anti-angiogenesis drug approved by the FDA that can be used in cancer treatment.These drugs, together with clinical and experimental progress in many other targeted drugs, have shown a favorable prospect for targeted drugs in the treatment of advanced non-small cell lung cancer.