We read with interest the Letter of the Editor from Silany et al., about our work that will published in Int J Cancer1: thus, we like to answer some of the questions mentioned:
First, we agree that the use of chemotherapy, specially during trimester will be consider very dangerous to the embryo, we calculated that chemotherapy was administered <2 weeks in 0 cases, between 3 to 8 weeks in 21 cases and between 9 to 14 weeks in 34 cases. In relationship to the absence of congenital malformations, we agree that our study reported an very low compared to other studies, different causes have been exposed to explain why congenital abnormalities did not appear in all children that received chemotherapy during pregnancy, specially during first trimester:
Increase in blood volume and renal clearance that can decrease active drug concentration.
A fasted hepatic-mixed function oxidase system might cause lower drug concentration.
Changes in volume distribution peak during and half-life of administration can change during pregnancy.
Association of multiple drug exposure that can increase or decrease the metabolism of cytotoxic drugs.2,3
Recently, it has been observed that the ATP-binding cassette (ABC) family predominantly localized in the maternal-facial syncisyal membrane of placental microvilli comprises the major placental drug transporter active efflux of drugs, by placental transporters help to maintain barrier function reducing the incidental adverse effects. All transporters polymorphisms way explain the wide variability observed in fetal drug concentrations, incidence of teratogenesis or drug failure in pregnancy exposed to therapeutic agents.4
We did not have any specific reason to explain why our children showed an low incidence of congenital malformations, we did not perform studies of drugs kinetics in fetus and neonatal biopsies to detect drugs concentrations in some tissues. Karp et al.5 showed that some drugs, as anthracyclines, can cross the placental barrier, but no clinical implications were observed in the fetus, German et al.6 studied children that received anthracyclines that have been associated to well-defined cardiac toxicity, and they did not found any evidence of cardiac damage. Thus, in absence of specific studies, we presumed that race could have any protection to avoid clinical malformations.7
In relation of the lost fetuses, in two cases autopsies were performed and no evidence of congenital abnormalities were observed, in the other two cases autopsied were denied but careful clinical evidence showed no evidence of any congenital malformations.
We agree that the use of chemotherapy, during pregnancy, specially during first trimester could be considered very dangerous to the embryo, and personal decision will be taken in each case.