title: Transplacental transfer of paclitaxel, docetaxel, carboplatin, and trastuzumab in a baboon model.
abstract: BACKGROUND
  The paucity of data on fetal effects of prenatal exposure to chemotherapy prompted us to study the transplacental transport of commonly used anticancer agents in a pregnant baboon model.
  
  
  METHODS
  Single or combination chemotherapy with paclitaxel, docetaxel, carboplatin, and trastuzumab was administered to 9 baboons at a mean (SD) gestational age of 117 (26) days (paclitaxel, 100 mg/m2 [n = 2]; docetaxel, 100 mg/m2 [n = 2]; paclitaxel, 175 mg/m2 with carboplatin, area under the curve of 6 at standard dosage [n = 2] and 50% dosage [n = 1]; docetaxel, 75 mg/m2 with carboplatin, area under the curve 6 [n = 1]; and docetaxel, 75 mg/m2 with trastuzumab, 8 mg/kg [n = 1]). Serial fetal and maternal blood samples, amniotic fluid, maternal urine, and fetal and maternal tissue samples were collected for the first 76 hours after drug infusion. Levels of carboplatin were determined by atomic absorption spectrometry, docetaxel and paclitaxel by high-performance liquid chromatography, and trastuzumab by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Fetal plasma concentrations of carboplatin averaged 57.5% (14.2%) of maternal concentrations (n = 7). Fetal plasma concentrations were 1.5% (0.8%) of maternal concentrations (n = 7). Immediately after ending the infusion, paclitaxel was not detectable in fetal tissues, whereas, after 3 hours, fetal tissues contained 15% of maternal tissue concentrations.Docetaxel could not be detected in fetal blood samples (n = 9). In the first 3 hours after docetaxel infusion, fetal tissues contained 5.0% to 50.0% of maternal tissue concentrations, whereas equal fetal and maternal tissue concentrations were found after 26 and 76 hours.The transplacental passages of trastuzumab were 85.0% and 3.0%, 2 and 26 hours after trastuzumab infusion, respectively. After 26 hours, amniotic fluid contained 36.4% of the fetal plasma concentration. Fetal tissue concentrations varied between 5.0% and 14.0% of the maternal concentration.
  
  
  CONCLUSIONS
  Variable plasma and/or tissue concentrations of taxanes, carboplatin, and trastuzumab were encountered in the fetal compartment. These data are important when cancer treatment is considered during pregnancy and underline the need for long-term follow-up of children after prenatal exposure to these cytotoxic agents.
authors.affiliation: Department of Obstetrics & Gynecology, Division of Gynecologic Oncology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Kristel Van
authors.initials: KV
authors.lastname: Calsteren
authors.forename: Rene
authors.initials: R
authors.lastname: Verbesselt
authors.forename: Roland
authors.initials: R
authors.lastname: Devlieger
authors.forename: Luc
authors.initials: L
authors.lastname: De Catte
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chai
authors.forename: Rieta
authors.initials: R
authors.lastname: Van Bree
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Heyns
authors.forename: Jos
authors.initials: J
authors.lastname: Beijnen
authors.forename: Sonia
authors.initials: S
authors.lastname: Demarsin
authors.forename: Ernst
authors.initials: E
authors.lastname: de Bruijn
authors.forename: Jan
authors.initials: J
authors.lastname: de Hoon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Amant
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000502:physiology; D016190:Carboplatin / Q000493:pharmacokinetics; D000077143:Docetaxel; D005260:Female; D005865:Gestational Age; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D023421:Models, Animal; D017239:Paclitaxel / Q000493:pharmacokinetics; D010215:Papio; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism; D043823:Taxoids / Q000493:pharmacokinetics; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D000068878:Trastuzumab; D017239:Paclitaxel