Dactinomycin]]>

Risk Factor: CM
Class: Antineoplastics

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References

Fetal Risk Summary

Dactinomycin is an antimitotic antineoplastic agent. Reproduction studies in the rat, rabbit, and hamster at IV doses three to seven times the maximum recommended human dose have shown embryo and fetal toxicity and teratogenic effects (1).

Normal pregnancies have followed the use of this drug prior to conception (2,3,4,5,6,7,8,9 and 10). Women, however, were less likely to have a live birth following treatment with this drug than with other antineoplastics (6).

Eight women who were treated with dactinomycin in childhood or adolescence subsequently produced 20 liveborn offspring, 3 (15%) of which had congenital anomalies (11). This rate was the highest among 14 antineoplastic agents studied. Another report, however, observed no major congenital malformations in 52 offspring born to 11 men and 25 women who had been treated with dactinomycin during childhood or adolescence, suggesting that the results of the initial study occurred by chance (12).

Reports on the use of dactinomycin in six pregnancies have been located (13,14,15,16,17 and 18). In these cases, dactinomycin was administered during the 2nd and 3rd trimesters and apparently normal infants were delivered. The infant from one of the pregnancies was continuing to do well 4 years after birth (15). Two of the other pregnancies (16,17) are discussed in more detail in the monograph for cyclophosphamide (see Cyclophosphamide).

Data from one review indicated that 40% of the infants exposed to anticancer drugs were of low birth weight (13). This finding was not related to the timing of exposure. Long-term studies of growth and mental development in offspring exposed to dactinomycin during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (19).

The long-term effects of combination chemotherapy on menstrual and reproductive function have been described in a 1988 report (20). Thirty-two of the 40 women treated for malignant ovarian germ cell tumors received dactinomycin. The results of this study are discussed in the monograph for cyclophosphamide (see Cyclophosphamide).

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 dactinomycin during human lactation or measuring the amount, if any, of the drug excreted into milk have been located. Although its relatively high molecular weight (about 1255) should impede the transfer into milk, women receiving this drug should not breast-feed because of the potential risk of severe adverse reactions in the nursing infant.

References

]]>

  1. Product information. Cosmegen. Merck, 2000.
  2. Ross GT. Congenital anomalies among children born of mothers receiving chemotherapy for gestational trophoblastic neoplasms. Cancer 1976;37:10437.
  3. Walden PAM, Bagshawe KD. Pregnancies after chemotherapy for gestational trophoblastic tumours. Lancet 1979;2:1241.
  4. Schwartz PE, Vidone RA. Pregnancy following combination chemotherapy for a mixed germ cell tumor of the ovary. Gynecol Oncol 1981;12:3738.
  5. Pastorfide GB, Goldstein DP. Pregnancy after hydatidiform mole. Obstet Gynecol 1973;42:6770.
  6. Rustin GJS, Booth M, Dent J, Salt S, Rustin F, Bagshawe KD. Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours. Br Med J 1984;288:1036.
  7. Evenson DP, Arlin Z, Welt S, Claps ML, Melamed MR. Male reproductive capacity may recover following drug treatment with the L-10 protocol for acute lymphocytic leukemia. Cancer 1984;53:306.
  8. Sivanesaratnam V, Sen DK. Normal pregnancy after successful treatment of choriocarcinoma with cerebral metastases: a case report. J Reprod Med 1988;33:4023.
  9. Lee RB, Kelly J, Elg SA, Benson WL. Pregnancy following conservative surgery and adjunctive chemotherapy for stage III immature teratoma of the ovary. Obstet Gynecol 1989;73:8535.
  10. Bakri YN, Pedersen P, Nassar M. Normal pregnancy after curative multiagent chemotherapy for choriocarcinoma with brain metastases. Acta Obstet Gynecol Scand 1991;70:6113.
  11. Green DM, Zevon MA, Lowrie 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;325:1416.
  12. Byrne J, Nicholson HS, Mulvihill JJ. Absence of birth defects in offspring of women treated with dactinomycin. N Engl J Med 1992;326:137.
  13. Nicholson HO. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynaecol Br Commonw 1968;75:30712.
  14. Gililland J, Weinstein L. The effects of cancer chemotherapeutic agents on the developing fetus. Obstet Gynecol Surv 1983;38:613.
  15. Haerr RW, Pratt AT. Multiagent chemotherapy for sarcoma diagnosed during pregnancy. Cancer 1985;56:102833.
  16. Weed JC Jr, Roh RA, Mendenhall HW. Recurrent endodermal sinus tumor during pregnancy. Obstet Gynecol 1979;54:6536.
  17. Kim DS, Park MI. Maternal and fetal survival following surgery and chemotherapy of endodermal sinus tumor of the ovary during pregnancy: a case report. Obstet Gynecol 1989;73:5037.
  18. Kim DS, Moon H, Lee JA, Park MI. Anticancer drugs during pregnancy: are we able to discard them? Am J Obstet Gynecol 1992;166:265.
  19. Dobbing J. Pregnancy and leukaemia. Lancet 1977;1:1155.
  20. Gershenson DM. Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors. J Clin Oncol 1988;6:2705.

Please enable JavaScript to view the comments powered by Disqus.blog comments powered by Disqus