Epirubicin: a new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature

Abstract

BackgroundCurrent knowledge indicate that epirubicin administration in late pregnancy is almost devoid of any fetal cardiotoxicity. We report a twin pregnancy complicated by breast cancer in which epirubicin administration was causatively linked to the death of one twin who was small for gestational age (SGA) and in a condition of oligohydramnios and determined the onset of a transient cardiotoxicity of the surviving fetus/newborn.Case presentationA 38-year-old caucasic woman with a dichorionic twin pregnancy was referred to our center at 20 and 1/7 weeks for a suspected breast cancer, later confirmed by the histopathology report. At 31 and 3/7 weeks, after the second chemotherapy cycle, ultrasound examination evidenced the demise of one twin while cardiac examination revealed a monophasic diastolic ventricular filling, i.e. a diastolic dysfunction of the surviving fetus who was delivered the following day due to the occurrence of grade II placental abruption. The role of epirubicin cardiotoxicity in the death of the first twin was supported by post-mortem cardiac and placental examination and by the absence of structural or genomic abnormalities that may indicate an alternative etiology of fetal demise. The occurrence of epirubicin cardiotoxicity in the surviving newborn was confirmed by the report of high levels of troponin and transient left ventricular septal hypokinesia.ConclusionBased on our findings we suggest that epirubicin administration in pregnancy should be preceded by the screening of some fetal conditions like SGA and oligohydramnios that may increase its cardiotoxicity and that, during treatment, the diastolic function of the fetal right ventricle should be specifically monitored by a pediatric cardiologist; also, epirubicin and desamethasone for lung maturation should not be closely administered since placental effects of glucocorticoids may increase epirubicin toxicity.

Does anthracycline-based chemotherapy in pregnant women with cancer offer safe cardiac and neurodevelopmental outcomes for the developing fetus?

“…Because glucocorticoids regulate in a complex manner the P-gp transport system at gene transcription and translation levels they could have contributed to the risk for damage from anthracycline exposure [ 73 ]. We also confirmed epirubicin cardiotoxicity by finding high troponin levels and transient left ventricular septal hypokinesia in the surviving newborn [ 72 ].…”

“…Conversely, although EPI has been considered devoid of cardiotoxic effects [ 66 – 70 ] one report describes transient ventricular hypokinesia [ 71 ]. In another report from our gynecological institute supported by myocardial and placental evidence we showed that epirubicin cardiotoxicity had a causative role in the death of a twin who died shortly after receiving glucocorticoids for lung maturation [ 72 ]. Because glucocorticoids regulate in a complex manner the P-gp transport system at gene transcription and translation levels they could have contributed to the risk for damage from anthracycline exposure [ 73 ].…”

“…In conclusion, cardiac toxicity during pregnancy or at birth therefore differs according to the type of anthracycline used. Despite rare toxicity reports [ 71 , 72 ], studies in large populations [ 55 , 64 ] imply that DOX and EPI have an acceptable safety profile.…”

Effects of cancer treatment during pregnancy on fetal and child development

“…53 Adverse cardiac foetal outcomes have been described after exposure to anthracyclines in utero, despite low transplacental passage. 14,18,54 Because of the different properties of the foetal myocardium as compared to the adult myocardium (single nucleus, fewer sarcomeres per mass unit, immature sarcoplasmic reticulum, lower number of mitochondria, underdeveloped antioxidant pathways), the foetal heart may be more vulnerable to anthracyclines. 55,56 Aviles et al reported the first study on the cardiac outcome after prenatal exposure to anthracyclines with normal echocardiographic findings for all children.…”

Chemotherapy during Pregnancy: Cases of Hodgkin's and Non-Hodgkin's Lymphoma, Chronic Myeloid Leukemia, Breast Cancer, Nasopharyngeal Cancer, and Choriocarcinoma

“…Due to their relatively low molecular weight, chemotherapeutic agents can cross the placenta and adversely affect the fetus [2][3][4]. Teratologic and other adverse fetal effects are dependent on dosage and the gestational age [5].…”