REPRODUCTIVE AND DEVELOPMENTAL TOXICITY STUDIES OF PACLITAXEL (II) : Intravenous administration to rats during the fetal organogenesis

Abstract

Paclitaxel, an antineoplastic agent, was administered intravenously to pregnant Crj: CD (SD) rats daily at dose levels of 0 (saline and vehicle), 0.15, 0.3 and 0.6 mg/kg from day 7 to day 17 of gestation. Results were as follows: 1. The ossification of hyoid bodies was retarded in F1 fetuses by the vehicle. However, the vehicle-treated group had no effect in the other parameters that were measured in this study when compared to the saline-treated group. 2. Body weight gains and food consumption in F0 dams were not affected by paclitaxel during the gestation and lactation periods. 3. Paclitaxel failed to affect the organ weights in F0 dams. 4. Paclitaxel did not alter the prenatal development in F1 fetuses. 5. External, internal and skeletal malformations were not induced by paclitaxel. Further, paclitaxel did not affect the skeletal variations and ossification processes. 6. Paclitaxel did not alter the delivery status of F0 dams or viability and weaning indices in F1 pups. 7. The day required for presence of hair was significantly delayed in 0.6 mg/kg F1 pups at paclitaxel. However, the days required for pinnae detachment, incisor eruption, eye opening, testicular descent and vaginal opening were not affected by paclitaxel. 8. No effects on body weight gains or food consumption were observed in both male and female F1 rats. 9. Paclitaxel did not alter the developmental behavior, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 10. The reproductive performance in both male and female F1 rats were not affected by paclitaxel. 11. Paclitaxel did not alter the organ weights in both male and female F1 rats. 12. No influence on prenatal development was observed for F2 fetuses even at the highest dose level of paclitaxel. Based on the reproductive and developmental indices, the no toxic-effect dose level of paclitaxel is 0.6 mg/kg/day and 0.3 mg/kg/day for dams (F0) and their offspring (F1), respectively.

Adnexal Masses in Pregnancy

“…High doses of paclitaxel (10 mg/kg/day) applied during early pregnancy (day 8 of gestation) were associated with reduced litter size, reduction of fetal weight, malformations including craniofacial malformations, diafragmatic hernias, and defects of the kidneys, the cardiovascular system, and the tail [38]. In contrast, exposure to lower dosages of paclitaxel (1.0 mg/kg/day) prior to mating, during mating, in early and in advanced pregnancy revealed no significant influence on reproductive outcome and subsequent locomotor-, or neuro-development [39][40][41]. Similar results were observed in pregnant rats treated with carboplatin.…”

Advanced Oral Tongue Cancer in a 22-Year-Old Pregnant Woman

“…Animal studies have shown toxicity to the fetus during organogenesis for taxanes and platinum-based agents, but given during the latter part of gestation, paclitaxel and cisplatin do not seem to have major effects on the fetus. 15,16 Paclitaxel can cause craniofacial malformations, anophthalmia, diaphragmatic hernia, and cardiac and renal malformations in rats when given early in the fetal period. 17 In a review of chemotherapy during pregnancy, Cardonick and Iacobucci 14 found only 5 of 24 cases of cisplatin use in pregnant women that were complicated by intrauterine growth retardation, intrauterine fetal demise, hearing loss, and/or ventriculomegaly.…”