Chemotherapy during pregnancy: pharmacokinetics and impact on foetal neurological development.

ABSTRACT

Based on an estimated incidence of cancer during pregnancy of 1 per 1000-1500 pregnancies, annualy 3000-5000 new patients can be expected in Europe. The treatment of cancer in pregnant women is a challenge since both the maternal and the foetal well-being need to be considered. This study was initiated to gain better insights into the problems associated with cancer and chemotherapy during pregnancy. A multicentric registration study was set up to evaluate the currently applied treatment modalities for cancer during pregnancy, and the consequences of their use for the pregnancy. Secondly, a preclinical and clinical pharmacological study addressing pharmacokinetics of chemotherapy in pregnant women and transplacental passage of chemotherapy was performed. Thirdly, we investigated the effects of prenatal exposure to chemotherapy on foetal neurological development. We observed an equal distribution of tumour types between pregnant and age matched nonpregnant women. Data on neonatal outcome suggest that exposure to chemotherapy in the 2nd or 3rd trimester of pregnancy does not worsen the outcome. This finding is explained by the fact that chemotherapy is not administered during the period of organogenesis and by the foetal protection by the placental barrier-function. Physiological changes of pregnancy resulted in a decreased plasma drug exposure of chemotherapeutic agents. Before major conclusions can be drawn with regard to the long term foetal outcome and the efficacy of chemotherapy during pregnancy, more patients and a longer follow up period is required. Therefore, this research project is continued and expanded nationally and internationally.