Cancer in Pregnancy: Daunorubicin

Daunorubicin (daunomycin; rubidomycin; Cerubidine) is an anthracycline glycoside antibiotic derived from Streptomyces peucetius and is used in cancer chemotherapy. It appears to act by interfering with nucleic acid synthesis.

	Setting	Treatment	Outcomes
	Species studied
Animal studies *	rat		Daunorubicin was teratogenic in rats ¹.
	rat, rabbit, hamster	1-4 times the human therapeutic dose	Increased frequencies of fetal death and of malformations of the heart, eye, and genitourinary tract were observed among the offspring of rats treated during pregnancy with daunorubicin ^2-3. This treatment was also toxic to the mothers. No teratogenic effect was observed among the offspring of hamster and of rabbits treated with less than the usual human dose of daunorubicin during pregnancy ³.
	mice		One study found daunorubicin not to be teratogenic in mice ²; however, another report indicated that the related carubicin was teratogenic in this animal ⁴.
	Study design
Human studies	Case reports	1st trimester exposure	There have been several reports of pregnant women treated with daunorubicin. Gililland and Weinstein ⁵ collected nine cases, one of which involved first trimester exposure. In this group there were no teratogenic effects, although two pregnancies were electively terminated, two were delivered prematurely, and two resulted in stillbirths (one of which showed myocardial necrosis, a possible drug effect). Since that review, other cases have been reported ^6-11. Four additional patients have been reported who received chemotherapy during the first trimester of pregnancy ^8,11; two of these women had apparently normal babies and two suffered spontaneous abortions within three weeks of treatment.
		2nd 3rd trimester	The remaining reports involved second and/or third trimester exposure. Complications of these pregnancies included premature delivery ^6,9, a diagnosis of "fetal distress" ⁶, and transient neonatal marrow suppression ^6,10. It is not possible to say whether an adverse pregnancy outcome, such as prematurity, is increased in women treated with daunorubicin since appropriate controlled studies have not been performed. If adverse outcomes are increased, it is at least theoretically possible that the maternal illness for which treatment is given and/or the co administration of other drugs may play a role. It has been generally concluded that cancer chemotherapy administered to women after the first trimester of pregnancy is compatible with normal births in the majority of cases ¹².
Breastfeeding			It is not known if Daunorubicin 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

Roux C, Taillemite JL: Actionteratogene de la rubidomycine chez le rat. CR Soc Biol 163:1299-1302,1969.
Roux C, Taillemite JL: Les effets de la rubidomycine sur le developpement embryonnaire chez le rat Wistar et Sprague-Dawley. chez la souris Swiss et le hamster Dore. Teratology 4:499, 1971.
Thompson DJ et al: Teratogenicity of adriamycin and daunomycin in the rat and rabbit. Teratology 17:151-8, 1978.
Damjanov I, Celluzi A: Embryotoxicity and teratogenicity of the anthracycline antibiotic carminomycin in mice. Res Commun Chem PatholPharmacol 28:497-504, 1980.
Gililland J, Weinstein L: The effects of cancer chemotherapeutic agents on the developing fetus. Obstet Gynecol Surv 38:6-13, 1983.
Colbert N et al: Acute leukemia during pregnancy: favourable course of pregnancy in two patients treated with cytosine arabinoside and anthracyclines. Nouv Presse Med 9:175-8, 1980.
Sanz MA, Rafecas FJ: Successful pregnancy during chemotherapy for acute promyelocytic leukemia. N Engl J Med 306:939, 1982.
Alegre A et al: Successful pregnancy in acute promyelocytic leukemia. Cancer 49:152-3, 1982.
Cantini E, Yanes B: Acute myelogenous leukemia in pregnancy. SouthMed J 77:1050-2, 1984.
Okun DB et al: Acute leukemia in pregnancy: transient neonatal myselosuppression after combination chemotherapy in the mother. MedPediatr Oncol 7:315-9, 1979.
Zuazu J, Julia A, Sierra J, et al.: Pregnancy outcome in hematologic malignancies. Cancer 67:703-709, 1991.
Blatt J et al: Pregnancy outcome following cancer chemotherapy. Am J Med 69:828-32, 1980.

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