Cancer in Pregnancy: Mechloroethamine

Mechloroethamine (nitrogen mustard) is an alkylating agent used as an antineoplastic.

	Setting	Treatment	Outcomes
	Species studied
Animal studies *	mice, rat, rabbits, ferrets		Mechloretamine is a potent teratogen in all species tested. It induces digital anomalies and hydrocephalus in mice ¹; multiple defects including cleft palate, central nervous system, jaw, limb and digit defects, chromosomal abnormalities in rats ²; and multiple malformations in rabbits ³ and ferrets ⁴.
	Study design
Human studies	Case reports	1st trimester	Nicholson reviewed 11 pregnancies with nitrogen mustard use, 6 during the first trimester. One pregnancy was terminated and 3 ended as spontaneous abortion. Of the 7 live births no one had any malformation ⁵.
			Two malformed children were reported:
		nitrogen mustard, vinblastine, procarbazine at 2 months of pregnancy, (six courses).	1. A spontaneously aborted male fetus at 24 weeks of gestation, with only four toes in both feet and partial syndactyly ⁶
		vincristine, procarbazine, nitrogen mustard and prednisone	2. A male fetus electively aborted with malpositioned kidneys of markedly reduced size. Karyotype performed on amniotic fluid cell culture was normal. ⁷
	Case series		No epidemiological studies of congenital anomalies among the infants of women treated with mechlorethamine during pregnancy. The following case series were located: 1. No congenital anomalies were observed in one series among 6 children born to women treated during pregnancy with cancer chemotherapeutic regimens that included mechloretamine. One of these women was treated during the first trimester ⁸. Their growth, intellectual development and cytogenetic analysis were normal in ages ranging from 3 - 19 years at the moment of the follow-up. 2. In a case series of 13 patients with first trimester exposure to cancer chemotherapy, 3 were exposed to combination regimens including mechloretamine. One pregnancy ended as a spontaneous abortion, one was electively terminated, and the last, a baby born with hydrocephalus, died 4 hours after birth ⁹

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

References

Danforth, C.H. and Center, E. Nitrogen Mustard as a teratogenic agent in the mouse. Proc Soc Exp Biol Med 1954;86:705-707.
Haskin, D. Some effects of nitrogen mustard on the development of external body form in the fetal rat. Anat Rec 1948; 102: 493-511.
Gottschewski, G.H.M. Mammalian blastopathies due to drugs. Nature1964; 201:1232-1233.
Mould, G.P., Curry, S.H., and Beck, F. The ferret, a useful model for teratogenic study. Naunyn Schimiedebergs Arch Pharmacol 1973; 279(Suppl):R-18.
Nicholson, H.O. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynaecol Br Commonw 1968; 75: 307-12.
Garret, M.J. Teratogenic effects of combination chemotherapy. Ann Intern Med 1974; 80:667.
Mennuti, M.T., Shepard, T.H., and Mellmann, W.J. Fetal renal malformation following treatment of Hodgkin's disease during pregnancy. Obstet Gynaecol 1975; 46: 194-196.
Aviles A, Diaz-Maqueo JC, Talavera A, et al. Growth and development of children of mothers treated with chemotherapy during pregnancy. Current status of 43 children. Am J Hematol. 36: 243-248,1991.
Zemlickis, D., et al. Fetal outcome after in utero exposure to cancer chemotherapy. Arch Intern Med 152: 573-576,1992.

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