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.

	Setting	Treatment	Outcomes
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.
	Species studied
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.
	Study Design
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.

* - None of the animal studies reported in this table were conducted at The Hospital for Sick Children, Toronto, or by Motherisk.

References

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.

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