Antineoplastic
PREGNANCY RECOMMENDATION: Contraindicated—1st Trimester
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Dacarbazine is an alkylating antineoplastic agent. Other agents in this class (see also Busulfan, Chlorambucil, and Cyclophosphamide) are known to be human teratogens and, combined with the animal data, strongly suggest that dacarbazine should not be given in the 1st trimester.
FETAL RISK SUMMARY
Single intraperitoneal doses of 800 or 1000 mg/kg in pregnant rats produced skeletal reduction defects, cleft palates, and encephaloceles in their offspring (1).
Dacarbazine was used for the treatment of melanoma in the 1st trimester of one pregnancy (2). The pregnancy was electively aborted. In a second case, a woman at 21 weeks’, received two cycles of chemotherapy for Hodgkin’s disease (3). Each cycle consisted of dacarbazine (375 mg/m2 IV, days 1 and 14), doxorubicin, bleomycin, and vinblastine. At 29 weeks’, a healthy, 2400-g female infant was born, who is alive and well at 10 years of age.
No congenital malformations were observed in four live-born offspring of one male and another female treated with dacarbazine during childhood or adolescence (4). In a 2002 study, 1915 women had 4029 pregnancies after chemotherapy with or without radiation (5). No statistical differences in pregnancy outcomes (live births and spontaneous abortions) by treatment group were found, including the 170 pregnancies in women treated with dacarbazine.
Occupational exposure of the mother to antineoplastic agents during pregnancy may present a risk to the fetus. A position statement from the National Study Commission on Cytotoxic Exposure and a research article involving some antineoplastic agents are presented in the monograph for cyclophosphamide (see Cyclophosphamide).
BREASTFEEDING SUMMARY
No reports describing the use of dacarbazine during lactation have been located. Because of the potential for severe adverse effects, such as hematopoietic depression in a nursing infant, the drug should not be used during breastfeeding.
References
1.Chaube S. Protective effects of thymidine, and 5-aminoimidazolecarboxamide and riboflavin against fetal abnormalities produced in rats by 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide. Cancer Res 1973;33:2231–40. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:189.
2.Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Sutcliffe SB, Koren G. Fetal outcome after in utero exposure to cancer chemotherapy. Arch Intern Med 1992;152:573–6.
3.Anselmo AP, Cavalier E, Maurizi Enrici R, Pescarmona E, Guerrisi V, Paesano R, Pachi A, Mandelli F. Hodgkin’s disease during pregnancy: diagnostic and therapeutic management. Fetal Diagn Ther 1999;14:102–5.
4.Green DM, Zevon MA, Lowries G, Seigelstein N, Hall B. Congenital anomalies in children of patients who received chemotherapy for cancer in childhood and adolescence. N Engl J Med 1991;325:141–6.
5.Green DM, Whitton JA, Stovall M, Mertens AC, Donaldson SS, Ruymann FB, Pendergrass TW, Robison LL. Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor study. Am J Obstet Gynecol 2002;187:1070–80.