Antineoplastic (Tyrosine Kinase Inhibitor)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
One report describing the use of gefitinib in the 2nd and 3rd trimesters has been located. There was developmental toxicity (growth restriction and death) in two animal species, but the very limited human pregnancy experience prevents a more complete assessment of the embryo–fetal risk.
FETAL RISK SUMMARY
Gefitinib is an oral epidermal growth factor receptor tyrosine kinase inhibitor. It is in the same subclass as several other agents (see Appendix). It is indicated as monotherapy for the continued treatment of patients with locally advanced or metastatic non-small-cell cancer after failure of other chemotherapies. Gefitinib is extensively metabolized and one of the metabolites is partially active. The elimination half-life of gefitinib is about 48 hours. Plasma protein binding to albumin and α-1 glycoprotein is 90% (1).
Reproduction studies have been conducted in rats and rabbits. Pregnant rats were treated from the beginning of organogenesis to the end of weaning with daily doses (5 mg/kg) that were about one-fifth the recommended human dose based on BSA (RHD), there was a decrease in the number of pups born alive. When the dose was increased to 20 mg/kg, the effect was more severe with more pups dying soon after birth. The no-effect dose was 1 mg/kg. In pregnant rabbits, a dose about twice the RHD caused reduced fetal weight (1). No mention of maternal toxicity was made in any of the animal studies.
Carcinogenicity studies have not been conducted with gefitinib. Genotoxicity studies in several tests were negative (1).
It is not known if gefitinib crosses the human placenta. After a single dose of 5 mg/kg (about one-fifth the RHD), gefitinib crossed the rat placenta (1). The molecular weight (about 447) and long elimination half-life suggest that gefitinib also will cross the human placenta.
A 2011 case report described a 38-year-old woman at 26 weeks’ gestation who was diagnosed with lung cancer (2). The woman had never smoked. She was initially treated with erlotinib 100 mg/day and then changed about 2 weeks later to gefitinib 250 mg/day. Gefitinib was continued through the remainder of her pregnancy. At 36 weeks’, she gave birth to a healthy 2.08-kg infant with an Apgar score of 9 at 1 minute. The baby weighed 2.98 kg 6 weeks later (2).
BREASTFEEDING SUMMARY
No reports describing the use gefitinib during human lactation have been located. The molecular weight (about 447) and long elimination half-life suggest that gefitinib will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown, but could be serious. In adults, the most common adverse effects were diarrhea, rash, acne, dry skin, nausea, and vomiting. Until human data are available, the safest course is to not breastfeed while taking gefitinib.
References
1.Product information. Iressa. AstraZeneca Pharmaceuticals, 2007.
2.Lee CH, Liam CK, Pang YK, Chua KT, Lim BK, Lai NL. Successful pregnancy with epidermal growth factor receptor tyrosine kinase inhibitor treatment of metastatic lung adenocarcinoma presenting with respiratory failure. Lung Cancer 2011;74:349–51.