Safety in treatment of hepatocellular carcinoma with immune checkpoint inhibitors as compared to melanoma and non-small cell lung cancer.
Safety in treatment of hepatocellular carcinoma with immune checkpoint inhibitors as compared to melanoma and non-small cell lung cancer.
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DOI：
10.1186/s40425-017-0298-2
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发表时间：
2017-11-21
影响因子：
10.9
通讯作者：
Greten TF
中科院分区：
文献类型：
--
作者：
Brown ZJ;Heinrich B;Steinberg SM;Yu SJ;Greten TF
肝细胞癌（HCC）是一个全球性的主要健康问题，发病率不断上升。由于HCC传统上发生在慢性炎症的肝脏中，这种炎症有助于推动肿瘤发生，并且通常使这些病变具有免疫原性，因此是免疫治疗的潜在靶点。由于HCC患者通常具有潜在的肝功能障碍，我们试图确定与黑色素瘤和非小细胞肺癌（NSCLC）相比，在天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）升高的胃肠道副作用方面，免疫检查点抑制剂在HCC患者中使用是否安全。和腹泻以及由于药物毒性和继发于药物毒性的死亡而退出研究的患者。对已完成的单药免疫检查点抑制剂治疗HCC、黑色素瘤和NSCLC患者的临床试验进行了文献综述。分析了胃肠道相关不良事件，包括天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）升高和腹泻，以及继发于药物相关毒性而停止治疗的患者和因治疗死亡的患者。我们发现，尽管与黑色素瘤和NSCLC患者相比，接受免疫检查点抑制剂治疗的HCC患者AST/ALT大幅增加，但这不会导致患者停止治疗或继发于药物毒性的死亡。我们建议免疫检查点抑制剂在HCC的治疗中是安全的。
Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity. A literature review was performed for clinical trials that have been completed with single agent immune checkpoint inhibitors for patients with HCC, melanoma, and NSCLC. Gastrointestinal related adverse events including elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea were analyzed as well as those patients who were taken off therapy secondary to drug related toxicity and patients who died as a result of therapy. We found that although patients with HCC treated with immune checkpoint inhibitors have a substantial increase in AST/ALT as compared to patients with melanoma and NSCLC, this does not cause the patients to come off therapy or cause death secondary to drug toxicity. We propose immune checkpoint inhibitors are safe to pursue in the treatment of HCC.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
DOI：
10.1056/nejmoa1504030
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Larkin J;Chiarion-Sileni V;Gonzalez R;Grob JJ;Cowey CL;Lao CD;Schadendorf D;Dummer R;Smylie M;Rutkowski P;Ferrucci PF;Hill A;Wagstaff J;Carlino MS;Haanen JB;Maio M;Marquez-Rodas I;McArthur GA;Ascierto PA;Long GV;Callahan MK;Postow MA;Grossmann K;Sznol M;Dreno B;Bastholt L;Yang A;Rollin LM;Horak C;Hodi FS;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
11.5
作者：
Kirkwood, John M.;Lorigan, Paul;Bulanhagui, Cecile A.
通讯作者：
Bulanhagui, Cecile A.
影响因子：
168.9
作者：
Bruix, Jordi;Qin, Shukui;Han, Guohong
通讯作者：
Han, Guohong