Cancer chemotherapeutic agents as human teratogens

BACKGROUND: Cancer is the second leading cause of death among women of reproductive age. Although the coincidence of pregnancy and cancer is rare and treatment may sometimes be safely delayed, the use of chemotherapeutic agents in pregnancy is sometimes unavoidable or inadvertent. METHODS: We review the literature for the use of antineoplastic agents in single-agent and combination therapy from 1951 through June 2012. We also summarize the evidence relating to teratogenicity of disorder-specific combination chemotherapy treatments for those malignancies frequently encountered in women of childbearing age. Major endpoints were called "adverse pregnancy outcomes" (APOs), to include structural anomalies (congenital malformations), functional defects, blood or electrolyte abnormalities, stillbirths, spontaneous abortions (miscarriages), and fetal, neonatal, or maternal deaths. RESULTS: The registry totals 863 cases. Rates of APOs (and congenital malformations) after any exposure were 33% (16%), 27% (8%), and 25% (6%), for first, second, and third trimesters. Among the groups of cancer drugs, antimetabolites and alkylating agents have the highest rates of APOs. Mitotic inhibitors and antibiotics seem more benign. Mixed results were observed from single-agent exposure, often because of small numbers of exposures. As a whole, the alkylating agents and antimetabolites are more harmful when given as a single agent rather than as part of a regimen. First-trimester exposure poses a more permanent risk to the fetus. CONCLUSIONS: Systematic ascertainment of women early in pregnancy, preferably in a population base, is needed for assessment of true risks. Long-term follow-up is needed to rule out neurobehavioral effects. Birth Defects Research (Part A) 94:626-650, 2012.