Daunorubicin

 Risk Factor: DM
 Class: ANTINEOPLASTICS

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Daunorubicin is a cytotoxic antibiotic used as an antineoplastic agent. In animal reproduction studies, exposure to daunorubicin during pregnancy produced teratogenic and toxic effects in rabbits, rats, and mice (1). In rabbits, a dose of 0.05 mg/kg/day (about 1/100th of the maximum recommended human dose on a body surface area basis) resulted in an increased incidence of abortions and fetal anomalies (parieto-occiptal cranioschisis, umbilical hernias, or rachischisis). Malformations in rats administered doses of 4 mg/kg/day (about 1/2 the human dose) included esophageal, cardiovascular, and urogenital malformations, as well as fused ribs. Retarded fetal and neonatal growth was observed in mice after maternal administration of daunorubicin (1).

The use of daunorubicin during pregnancy has been reported in 29 patients, four during the 1st trimester (2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18 and 19). No congenital defects were observed in the 22 (one set of twins) liveborns, but one of these infants was anemic and hypoglycemic and had multiple serum electrolyte abnormalities (8). Two infants had transient neutropenia at 2 months of age (4). Severe, transient, drug-induced bone marrow hypoplasia occurred in one newborn after in utero exposure to daunorubicin and five other antineoplastic agents (18). The myelosuppression was probably secondary to mercaptopurine. The infant made an uneventful recovery. Results of the remaining pregnancies were three elective abortions (one with enlarged spleen), three intrauterine deaths (one probably due to severe pregnancy-induced hypertension), one stillborn with diffuse myocardial necrosis, and one maternal death (8,9,15,17). Thirteen of the infants (including one set of twins) were studied for periods ranging from 6 months to 9 years and all showed normal growth and development (4,9,10 and 11,14,15,17,18 and 19).

Data from one review indicated that 40% of the infants exposed to anticancer drugs were of low birth weight (20). This finding was not related to timing of the exposure. Except for the infants noted above, long-term studies of growth and mental development in offspring exposed to daunorubicin during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (21).

In one report, the use of daunorubicin and other antineoplastic drugs in two males was thought to be associated with congenital defects in their offspring (22). The defects observed were tetralogy of Fallot and syndactyly of the first and second digits of the right foot, and an anencephalic stillborn. Although the authors speculated that the drugs damaged the germ cells without producing infertility and thus were responsible for the defects, any relationship to paternal use of daunorubicin is doubtful due to the lack of experimental evidence and other confirming reports. In a third male, fertilization occurred during treatment with daunorubicin and resulted in the birth of a healthy infant (23). Successful pregnancies have also been reported in two women after treatment with daunorubicin (24).

Chromosomal aberrations were observed in the fetus of a 34-year-old woman with acute lymphoblastic leukemia who was treated with multiple antineoplastic agents (12). Daunorubicin was administered for approximately 3 weeks beginning at 22 weeks' gestation. A healthy female infant was delivered 18 weeks after the start of therapy. Chromosomal analysis of the newborn revealed a normal karyotype (46,XX), but with gaps and a ring chromosome. The clinical significance of these findings is unknown, but since these abnormalities may persist for several years, the potential existed for an increased risk of cancer as well as for a risk of genetic damage in the next generation (12).

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).

Breast Feeding Summary

No reports describing the use of daunorubicin during lactation have been located. Because of the potential for severe toxicity in a nursing infant, the use of this agent is contraindicated during breast feeding.

References

1. Product information. Cerubidine. Bedford Laboratories, 2000.
2. Sears HF, Reid J. Granulocytic sarcoma: local presentation of a systemic disease. Cancer 1976;37:180813.
3. Lilleyman JS, Hill AS, Anderton KJ. Consequences of acute myelogenous leukemia in early pregnancy. Cancer 1977;40:13003.
4. Colbert N, Najman A, Gorin NC, Blum F. Acute leukaemia during pregnancy: favourable course of pregnancy in two patients treated with cytosine arabinoside and anthracyclines. Nouv Presse Med 1980;9:1758.
5. Tobias JS, Bloom HJG. Doxorubicin in pregnancy. Lancet 1980;1:776.
6. Sanz MA, Rafecas FJ. Successful pregnancy during chemotherapy for acute promyelocytic leukemia. N Engl J Med 1982;306:939.
7. Alegre A, Chunchurreta R, RodriguezAlarcon J, Cruz E, Prada M. Successful pregnancy in acute promyelocytic leukemia. Cancer 1982;49:1523.
8. Gililland J, Weinstein L. The effects of cancer chemotherapeutic agents on the developing fetus. Obstet Gynecol Surv 1983;38:613.
9. Feliu J, Juarez S, Ordonez A, Garcia-Paredes ML, Gonzalez-Baron M, Montero JM. Acute leukemia and pregnancy. Cancer 1988;61:5804.
10. Volkenandt M, Buchner T, Hiddemann W, Van De Loo J. Acute leukaemia during pregnancy. Lancet 1987;2:15212.
11. Turchi JJ, Villasis C. Anthracyclines in the treatment of malignancy in pregnancy. Cancer 1988;61:43540.
12. Schleuning M, Clemm C. Chromosomal aberrations in a newborn whose mother received cytotoxic treatment during pregnancy. N Engl J Med 1987;317:16667.
13. Gokal R, Durrant J, Baum JD, Bennett MJ. Successful pregnancy in acute monocytic leukaemia. Br J Cancer 1976;34:299302.
14. Lowenthal RM, Marsden KA, Newman NM, Baikie MJ, Campbell SN. Normal infant after treatment of acute myeloid leukaemia in pregnancy with daunorubicin. Aust NZ J Med 1978;8:4312.
15. O'Donnell R, Costigan C, O'Connell LG. Two cases of acute leukaemia in pregnancy. Acta Haematol 1979;61:298300.
16. Hamer JW, Beard MEJ, Duff GB. Pregnancy complicated by acute myeloid leukaemia. NZ Med J 1979;89:2123.
17. Doney KC, Kraemer KG, Shepard TH. Combination chemotherapy for acute myelocytic leukemia during pregnancy: three case reports. Cancer Treat Rep 1979;63:36971.
18. Okun DB, Groncy PK, Sieger L, Tanaka KR. Acute leukemia in pregnancy: transient neonatal myelosuppression after combination chemotherapy in the mother. Med Pediatr Oncol 1979;7:3159.
19. Cantini E, Yanes B. Acute myelogenous leukemia in pregnancy. South Med J 1984;77:10502.
20. Nicholson HO. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynaecol Br Commonw 1968;75:30712.
21. Dobbing J. Pregnancy and leukaemia. Lancet 1977;1:1155.
22. Russell JA, Powles RL, Oliver RTD. Conception and congenital abnormalities after chemotherapy of acute myelogenous leukaemia in two men. Br Med J 1976;1:1508.
23. Matthews JH, Wood JK. Male fertility during chemotherapy for acute leukemia. N Engl J Med 1980;303:1235.
24. Estiu M. Successful pregnancy in leukaemia. Lancet 1977;1:433.
    
    

Questions and Answers

How could the hemogloblin count go up during chemotherapy?, I got some results that show that as a patient was getting chemotherapy (Daunorubicin and Cytarabine), the amoutn of white blood cells and platelets went down, but the mass of hemogloblin per Liter went up. Anybody able to explain this?

Possible that the patient being treated with a red blood cell booster drug like Arnasep or Procrit? (i.e. EPO.)

My hemoglobin was ridiculously low at diagnosis for advanced stage Hodgkin's Disease -- it was actually around 7.0. So I started getting Arnasep shots and it increased despite the chemo. Once it hit 11.0, the Arnasep was discontinued, but my hemoglobin still kept climbing despite the chemo. If the patient was like me and had a heavy disease burden, perhaps knocking back the cancer is allowing the body and bone marrow to function better.

Would also consider dehydration -- makes the blood more concentrated which can make the hemoglobin level seem higher.