Department of Pharmacy, Meander Medical Center, Utrechtseweg 160, 3818ES Amersfoort, The Netherlands.
Lung Cancer. 2012 Mar;75(3):391-7. doi: 10.1016/j.lungcan.2011.10.008. Epub 2011 Nov 17.
Erlotinib is an agent in the class of oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Although this class of agents is considered to be relatively safe, the most serious, but rare, adverse reaction is drug-associated interstitial lung disease (ILD). This potentially fatal adverse reaction has been often described with gefitinib, but has been less well described for erlotinib. We here describe a case report of fatal interstitial lung disease in a Caucasian man associated with erlotinib and high erlotinib and metabolite plasma levels and discuss it in the context of all documented cases of erlotinib associated ILD.
Our case was described and for the literature review a Pubmed and Google Scholar search was conducted for cases of erlotinib associated ILD. The retrieved publications were screened for relevant literature.
Besides our case, a total of 19 cases of erlotinib-associated ILD were found. Eleven out 19 cases had a fatal outcome and in only one case erlotinib plasma concentrations were measured and found to be high.
Erlotinib-associated ILD is a rare, serious and often fatal adverse reaction. Most likely, the cause for erlotinib-associated ILD is multifactorial and high drug levels may be present in patients without serious adverse reactions. However, considering the pharmacology of EGFR inhibitors, high drug and metabolite levels may play a role and future studies are warranted to identify risk factors and to investigate the role of elevated levels of erlotinib and its metabolites in the development of pulmonary toxicity.
厄洛替尼是一种口服表皮生长因子受体（EGFR）酪氨酸激酶抑制剂类药物。尽管此类药物被认为相对安全，但最严重但罕见的不良反应是药物相关性间质性肺病（ILD）。这种潜在致命的不良反应在吉非替尼中经常被描述，但在厄洛替尼中描述得较少。我们在此报告 1 例与厄洛替尼相关的致命性间质性肺病病例，并结合所有已发表的厄洛替尼相关 ILD 病例进行讨论。
我们对 1 例病例进行了描述，并通过 Pubmed 和 Google Scholar 检索了与厄洛替尼相关 ILD 的文献，对检索到的出版物进行了筛选，以获取相关文献。
除了我们的病例外，还发现了总共 19 例与厄洛替尼相关的 ILD。19 例中有 11 例死亡，仅有 1 例测量了厄洛替尼的血浆浓度，发现浓度较高。
厄洛替尼相关性 ILD 是一种罕见、严重且常致命的不良反应。最有可能的是，厄洛替尼相关性 ILD 的原因是多因素的，即使没有严重不良反应，也可能存在药物水平较高的情况。然而，考虑到 EGFR 抑制剂的药理学，高药物和代谢物水平可能起作用，需要进一步研究来确定风险因素，并探讨厄洛替尼及其代谢物水平升高在肺毒性发展中的作用。
