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Motherisk Update 2014
Fetal Alcohol Canadian Expertise (FACE) Satellite Meeting,
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Current Studies at Motherisk
Neurodevelopment of Children Exposed in-Utero to Chemotherapy for Maternal Breast Cancer (Dr. I Nulman)
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Cancer in Pregnancy: Dacarbazine
Dacarbazine is an antineoplastic agent that appears to act bycross-linking DNA strands. It is administered intravenously in the treatment of malignant melanoma, Hodgkin's disease, and other malignancies.
|In vitro studies||Animal marrow cells||Genotoxicity analysis of bone marrow cells collected from mice after 24 to72 h of exposure to dacarbazine showed an inhibition of cell division and an increase in the incidence of chromatid gaps and breaks 1.|
|Animal studies *||rats, rabbits||intraperitoneally, 200-1000 mg/kg||The drug was teratogenic in rats and rabbits, producing anomalies such as cleft palate, encephaloceles, and skeletal defects 2,3. Increased frequencies of central nervous system, limb, and craniofacial anomalies have been observed among the offspring of rats treated with 22-220 times the usual human dose of dacarbazine during pregnancy 2. On days 11 or 12 a single dose of 800 or 1000 mg per kg produced skeletal reduction defects and some cleft palates and encephaloceles. The teratogenic effect exhibited typical time of gestation and dose dependence. Increased frequencies of cleft palate and skeletal anomalies were seen among the offspring of rabbits treated with only about twice the human therapeutic dose of dacarbazine; maternal toxicity was also observed at this dose 3.|
|Human studies||No epidemiological studies of congenital anomalies in infants born to women treated with dacarbazine during pregnancy have been reported.|
|Case report||2nd trimester exposure||While dacarbazide has been teratogenic in animals 4, it had no untoward effects on the infant of a 30-year-old woman who was treated for malignant melanoma during her fourth month of pregnancy. The patient received 2 courses of intravenous drug. She had marked improvement in her condition after the first course, but not after the second course, and she eventually died on the tenth day postpartum. The infant presented with no teratogenic effects, but had withdrawal symptoms secondary to meperidine and hydromorphone exposure during gestation 5.|
|Case series||1st trimester exposure||No congenital anomalies occured among 17 women treated with this drug and other antineoplastics 4. Seven were treated during the first trimester 4.|
|Breastfeeding||It is not known if Dacarbazide is excreted in breast milk. However, manufacturer contraindicate breastfeeding during treatment.|
- Al-Hawary BA, Al-Saleh AA: Cytogenetic effects of dacarbazine on mouse bone marrow cells in vivo. Mutat Res223:259-266, 1989.
- Chaube S: Protective effects of thymidine, 5-aminoimidazole carboxamide, and riboflavin against fetal abnormalities produced in rats by5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide. Cancer Res 33:2231-40,1973.
- Thompson DJ, Mollelo JA, Strebing RJ, Dyke IL: Reproductive and teratology studies with oncolytic agents in the rat and rabbit. II.5-(3,3-Dimethyl-1- triazeno)imidazole-4-carboxamide (DTIC). Toxicol Appl Pharmacol 33:281-90, 1975.
- DRUGDEX, Dacarbazide, Drug Evaluation, Micromedex, Inc. Volume 97.
- Toussi T, Blais M, Langevin P et al: Metastatic melanoma treated in a pregnant woman: Pre- and postnatal implications. Un Med Canada 1974;103:1968-1973.
- Aviles, A.; Diaz-Maqueo, J.C.; Talavera, A.; Guzman, R. and Garcia, E.L Growth and development of children of mothers treated with chemotherapy during pregnancy: Current status of 43 children. Am J Hematol 36:243-248, 1991.