Table 4.
Preclinical and clinical data on placental transfer for most common cytotoxic drugs used for gastric cancer
| Drug | Drug characteristicsa | Pre‐clinical data (placental transfer) | Reference | Clinical data | Reference |
|---|---|---|---|---|---|
| 5‐FU (Fluorouracil) | MWb: 130 g/mol Negligible PB (8%‐12%) | 28% (rat model) | Boike et al20 | Large case series on use of anthracycline‐based chemotherapy (including FEC and FAC) during pregnancy in breast cancer patients; use during second and third trimester of pregnancy seems relatively safe. | Amant et al19 Cardonick et al25 |
| Capecitabine (prodrug of 5‐FU) | MWb: 359 g/mol Limited PB (<60%) | No data | One case report, colorectal cancer, treated in first trimester; no congenital malformations | Cardonick et al25 | |
| Platinum‐derivates Oxaliplatin Cisplatin Carboplatin | MWb: 397 g/mol High PB (>90%) MWb: 298 g/mol, High PB (>90%) MWb: 371 g/mol Limited PB (25%‐40%) | No data 2%‐24% (ex vivo placental perfusion model) up to 57% (baboon model) | Al‐Saleh et al21 Van Calsteren et al22 | Few case reports on oxaliplatin (one case of neonatal hypothyroidism in 8 patients treated with FOLFOX for colorectal cancer) Reports of hearing loss when cisplatin used during pregnancy. Carboplatin appears to be a safer alternative. | Pellino et al26 Amant et al19 |
| Epirubicin | MWb: 543 g/mol Moderate PB (~77%) | Less than 10% (baboon model) | Van Calsteren et al23 | Large case series on use of anthracycline‐based chemotherapy during pregnancy in breast cancer patients; use during second and third trimester of pregnancy seems relatively safe. | Amant et al19 Cardonick et al25 |
| Taxanes Paclitaxel Docetaxel | MWb: 854 g/mol High PB (89%‐98%) MWb: 808 g/mol High PB (94%‐97%) Drug efflux by placental p‐glycoprotein transporter | Low (<2%, paclitaxel) or undetectable (docetaxel) in fetal plasma, but accumulation in fetal tissue (metabolization of taxanes still immature) (baboon model) Paclitaxel modulates expression of placental drug transporters of anticancer agents (ex vivo placental perfusion model) | Van Calsteren et al22 Berveiller et al24 | Favorable toxicity profile in small case series when administered during second or third trimester of pregnancy (12‐25 patients) | Cardonick et al27 |
| Trastuzumab | IgG monoclonal antibody MWb: 14 5531 g/mol | Placental transfer by specific receptor‐mediated active transport (not active in early pregnancy), up to 85% (baboon model) | Van Calsteren et al22 | Risk of oligohydramnios, hypoplastic lungs and fetal death by its ligation to HER2‐receptors that are present in the renal epithelium of the fetus Exclusive exposure during first trimester of pregnancy appears not to be associated with abnormalities (HERA trial) | Azim et al28 |
Abbreviations: FAC, 5‐FU, adriamycin (doxorubicin), cyclophosphamide; FEC, 5‐FU, epirubicin, cyclophosphamide; 5‐FU, 5‐fluorouracil; FOLFOX, 5‐FU and oxaliplatin; HER2, human epidermal growth factor receptor 2; HERA, Herceptin Adjuvant Trial; MW, molecular weight; PB, protein binding.
a
Reference for drug characteristics: Drugbank 5.0.29
b
Agents with low molecular weight (<500 g/mol) and low protein binding will easily cross the placenta.