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Current Studies at Motherisk
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Cancer in Pregnancy: Paclitaxel
Paclitaxel (Taxol) is an antineoplastic obtained from the Pacific northwest yew tree. The drug prevents the depolymerization of tublin, resulting in unrestricted accumulation of microtubles within cells. Microtubles are important in a number of cellular processes, including locomotion, transport, and secretion, as well as providing the framework on which chromatids separate in mitosis.
|In vitro studies||mouse embryo||Compaction, which occurs in the morula, is inhibited in the mouse embryo 1.|
|chick embryos||Expansion of the hypoblast in the cultured chick embryos is also inhibited by paclitaxel 2. Administered later in development, paclitaxel causes abnormal mitotic figures in chick cardiac endothelial cells 3.
Scialli et al ('92) found cardiovascular hemorrhages and decreased eye pigment in chick embryos exposed to 14 mmole and above 4. In studies using albumen injected liposome-encapsulated taxol Scialli et al ('95) found that the toxicity was only one-twentieth of that produced by taxol in cremaphor 5.
|Animal studies *||rats and rabbits||Studies reported by the manufacturer (Bristol-Myers Oncology, Princeton NJ) in rats and rabbits showed an increase in embryolethality associated with maternal toxicity, but no increase in birth defects 6.|
|rats||up to 0.6 mg/kg/day||Another study, reported in abstract, found that pregnant rats showed no maternal or embryotoixicity except a decrease in pup hair growth at the top dose 7.|
|1 mg/kg/day during late pregnancy and location||When rats were given up to 1mg/kg/day during late pregnancy and location, maternal toxicity occurred at the top dose accompanied by delayed hair and incisor growth, delayed testicular descent, and decreased weight in the pups 5.|
|Human studies||No epidemological studies of congenital anomalies in infants born to women who used this drug during pregnancy have been reported.|
|Breast feeding||It is not known if paclitaxel is excreted in breast milk.|
- Maro B, Pickering SJ. Microtubules influence compaction in preimplantation mouse embryos. JEmbryol Exp Morphol 1984; 84:217-32.
- Mareel M, Bellairs R, De Bruyne G,Van Peteghem MC. Effect of microtubule inhibitors on the expansion of hypoblast and margin of overgrowth of chick blastoderms. J Embryol ExpMorphol 1984; 81:273-86.
- Garcia-Martinez V, Hurle JM. Effects of taxol on endothelial cells of the developing semilunar heart valves in the chick embryo. Acta Anat(Basel) 1988;133:282-8.
- Scialli, A.R.; DeSesso, J.M. and Goeringer, G.C.: Taxol toxicity in the developing chick (A). Teratology 45:478, 1992.
- Scialli, A.R.; DeSesso, J.M.;Rahman, A.; Husain, S.R. and Goeringer, G.C.: Embryotoxicity of free and liposome-encapsulated taxol in the chick. Pharmacology 51:145-151, 1995.
- Paclitaxel, In: 1974-1998 Micromedex, Inc. Volume 97, Reprotox 1998.
- Lochry E, Kai S, Kohmura H, Kadota T, Takahashi N. Reproductive safety evaluation of paclitaxel in rats. Toxicologist 1995;15:165.