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

Abstract

BackgroundCancer treatment during pregnancy is a growing problem especially now that women delay childbearing. Systemic treatment of these malignancies during pregnancy centers mainly on the anticancer drugs anthracyclines, widely used in treating hematological and breast cancer during pregnancy and sometimes associated with early and late toxicity for the fetus. Owing to concern about their cardiac and neurodevelopmental toxicity more information is needed on which anthracycline to prefer and whether they can safely guarantee a cardiotoxicity-free outcome in the fetus.DiscussionThe major research findings underline anthracycline-induced dose-dependent effects, including cardiotoxicity, many avoidable. Partly because the placenta acts mainly as a barrier, research findings indicate low transplacental anthracycline transfer. Anthracycline-induced teratogenicity depends closely on when patients receive chemotherapy. Anthracycline cardiac toxicity may depend on the association with drugs that inhibit or induce placental P-glycoprotein (P-gp). P-gp-induced drug interactions may alter placental P-gp barrier function and subsequently change fetal exposure. Though many anthracyclines have acceptable safety profiles clinical studies suggest giving idarubicin with special caution. Patients and doctors who care for pregnant women should whenever possible avoid prematurity and hence reduce prematurity-induced medical complications at birth and in the long-term. Information is lacking on long-term anthracycline-induced effects.ConclusionPregnant women receiving anthracycline-based chemotherapy should undergo regular, state-of-the-art diagnostic imaging to detect fetal drug-induced cardiac damage early, and allow alternative therapeutic options. Recognizing drug-induced interactions and understanding the most vulnerable fetuses will help in choosing tailored therapy. Future research on placental transport, blood-brain barrier drug passage and pharmacokinetics will improve the way we manage these difficult-to-treat patients and their fetuses.

Oncological management of pregnancy-associated cancers: analysis from the French CALG (Cancer Associé à La Grossesse) network

“…A meta-analysis by Song et al including 39 studies published between 1997 and 2018 demonstrated that neoadjuvant platinum-based chemotherapy was a good option to manage uterine cervical cancer during the second and third trimesters [23]. In the same way, several studies have shown the good prognosis of children exposed to anthracyclines during pregnancy [24][25][26] although this regimen raises concerns about fetal cardiac toxicity [27]. Similarly, taxanes can also be used after the first trimester of pregnancy [28].…”

The use of 5-azacytidine in pregnant patient with Acute Myeloid Leukemia (AML): a case report

“…Some anthracyclines, such as doxorubicin and daunorubicin are safer during pregnancy. Idarubicin is more lipophilic and has an increased risk of crossing the placenta with a higher rate of potential fetal complications than the other anthracyclines [17, 18]. Therefore, idarubicin should be avoided during pregnancy.…”

The role of imaging techniques in the diagnosis, staging and choice of therapeutic conduct in pregnancy associated breast cancer

“…Chemotherapeutic agents most commonly used in pregnancy are anthracyclines and alkylating agents. Furthermore, the use of the FAC regimen (5FU, Doxorubicin, Cyclophosphamide) appears to be associated with a low risk of complications and fetal malformations when administered in the 2 nd and 3 rd trimesters of pregnancy [4,37].…”