Evidence on possible neonatal risks after pre-natal exposure to targeted therapy and tamoxifen
| Drug | Function | Cancer type | Neonatal risk | Recommendation for use during pregnancy | Reference |
| Trastuzumab | Her2-receptor inhibitor | Breast cancer, gastric cancer | Oligohydramnios, hypoplastic lungs and fetal death by its ligation to Her2-receptors that are present in the renal epithelium of the fetus | Not to use | 25 26 |
| Imatinib | Tyrosine kinase inhibitor | Chronic myeloid leukemia | Exposure in first trimester associated with congenital malformations (11% of exposed fetuses) and spontaneous miscarriage. Safety data for exposure in second or third trimester are limited but no major minor congenital malformations are reported | To use with caution | 25 |
| Rituximab | Anti-CD20 monoclonal antibody | Non-Hodgkin's lymphoma | Neonatal cytopenia, no congenital malformations reported Potential maternal benefits should be weighed against limited fetal risks | To use with caution | 25 26 |
| Interferon-α | Pleiotropic cytokine | Melanoma, CML, lymphoma, hairy cell leukemia and AIDS-related Kaposi sarcoma | Dose-dependent increased miscarriage rate in animal models. Limited placental transfer. One case reported with congenital malformations (exomphalos, right renal agenesis, and hemivertebrae), out of 43 cases, 2% | Can be used during pregnancy on strict indication | 25 |
| Epidermal growth factor receptor inhibitors: erlotinib, gefitinib, afatinib, and cetuximab | EGFR is involved in cell proliferation and differentiation and has been implicated in various stages of embryonic development | (Metastatic) lung cancer | Limited data. Increased risk of miscarriage in animal models. three cases with erlotinib during pregnancy revealed no congenital malformations. More safety data is needed | Not to use | 25 |
| Anti-angiogenetic agents: (1) bevacizumab, (2) sorafenib, (3) sunitinib | Vasculogenesis and angiogenesis in the human placenta and for normal fetal development | Advanced stage solid tumors (1), renal cell carcinoma (RCC), thyroid cancer and liver cancer (2), advanced RCC | Embryo-fetal death, (skeletal) congenital malformations in animal models. No human data for sorafenib and sunitinib. Intravitrealinjections of bevacizumab was not associated with adverse events | Not to use | 25 |
| BRAF-inhibitor: vemurafenib | Inhibition of BRAF, proto-oncogen | Advanced melanoma | Limited data. No teratogenesis reported in animal models. One case report of low birth weight and preterm delivery (administration after 25 weeks of gestation); one case of toxic epidermal necrolysis and fatal maternal outcome | Not to use | 25 |
| Tamoxifen | Selective estrogen receptor modulator | Breast cancer | Intra-uterine fetal death and birth defects like Goldenhar syndrome (oculo-auriculo-vertebral dysplasia), ambiguous genitalia and Pierre Robin sequence (triad of small mandible, cleft palate, and glossoptosis | Not to use | 28 |
EFGR, epidermal growth factor receptor.