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Cancer in Pregnancy: Mechloroethamine
Mechloroethamine (nitrogen mustard) is an alkylating agent used as an antineoplastic.
|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.|
|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|
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
- 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.