Gil S, Goetgheluck J, Paci A, Broutin S, Friard S, Couderc L J, Ayoubi J M, Picone O, Tcherakian C
Inserm, UMRS-1139, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; PremUp Foundation, Paris, France.
Service de gynécologie-obstétrique, hôpital Foch, 40 rue Worth, Suresnes, France.
Lung Cancer. 2014 Sep;85(3):481-4. doi: 10.1016/j.lungcan.2014.06.003. Epub 2014 Jun 16.
The incidence of lung cancer is rising in pregnancy, which is diagnosed on stage III-IV in 98%. Almost half of these patients are non-smokers, who are associated with more epidermal growth factor receptor (EGFR)-mutated lung cancer. As cytotoxic chemotherapy is associated with poor outcome for mothers and prematurity for children this will probably lead to repeatedly question the use of EGFR-Tyrosine kinase inhibitors (TKI) (i.e. gefitinib and erlotinib) during pregnancy for EGFR-mutated lung cancer. EGFR-TKIs are recommended as the first line targeted therapy in case of advanced non small cell lung carcinoma (NSCLC) with an activating EGFR mutation but not recommended during pregnancy due to lack of data. We report clinical and pharmacological data for gefitinib during pregnancy in both the mother and fetus and resume the literature on the subject. A 33-year-old pregnant mother exhibited a disseminated EGFR-mutated lung carcinoma with respiratory distress at 26 weeks of pregnancy. Gefitinib administration was associated with rapid maternal respiratory improvement allowing a planned cesarian section on week 35, giving birth to a healthy baby (2575g) with regular development at 24 months of follow-up. The mother exhibited a progression-free survival of 42 weeks with an overall survival of 22 months. Gefitinib residual concentration was found in cord blood at 25.7ng/mL, confirming a transplacental transfer, but at only 20% of the maternal concentration measured at the same time (i.e. 127.1ng/mL). Gefitinib concentration in amniotic fluid, which represents chronic fetal exposure to the drug, was also 20% of the maternal residual concentration (16.9ng/mL) and reflected no fetal accumulation of the drug, despite both long half time elimination of gefitinib (i.e. 48h) and long time exposure (i.e. 55 days). This low transplacental transfer is an important report, as potential side effect toxicity on the fetus is likely correlated to gefitinib blood concentration.
肺癌在妊娠期的发病率呈上升趋势，其中98%在Ⅲ-Ⅳ期被诊断出来。这些患者中近一半是非吸烟者，与更多的表皮生长因子受体（EGFR）突变型肺癌相关。由于细胞毒性化疗对母亲预后不良且会导致胎儿早产，这可能会反复引发对于在妊娠期使用EGFR-酪氨酸激酶抑制剂（TKI）（即吉非替尼和厄洛替尼）治疗EGFR突变型肺癌的质疑。EGFR-TKIs被推荐作为晚期非小细胞肺癌（NSCLC）伴有激活型EGFR突变时的一线靶向治疗药物，但由于缺乏相关数据，不建议在妊娠期使用。我们报告了吉非替尼在妊娠期母亲和胎儿体内的临床及药理学数据，并总结了该主题的文献。一名33岁的孕妇在妊娠26周时表现为播散性EGFR突变型肺癌并伴有呼吸窘迫。给予吉非替尼治疗后，母亲的呼吸迅速改善，得以在第35周进行计划剖宫产，产下一名健康婴儿（2575克），随访24个月时发育正常。母亲的无进展生存期为42周，总生存期为22个月。在脐带血中发现吉非替尼残留浓度为25.7纳克/毫升，证实了药物的经胎盘转运，但仅为同时测得的母亲体内浓度（即127.1纳克/毫升）的20%。羊水内的吉非替尼浓度代表胎儿长期暴露于该药物的情况，也为母亲残留浓度的20%（16.9纳克/毫升），尽管吉非替尼的消除半衰期较长（即48小时）且暴露时间较长（即55天），但未显示出胎儿体内药物蓄积。这种低经胎盘转运是一项重要发现，因为对胎儿潜在的副作用毒性可能与吉非替尼的血药浓度相关。
