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Neurodevelopment of Children Exposed in-Utero to Chemotherapy for Maternal Breast Cancer (Dr. I Nulman)
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Cancer in Pregnancy: Bleomycin
Bleomycin (Blenoxane) is a glycopeptide antibiotic used in the chemotherapy of some neoplastic diseases. Bleomycin sulfate is commonly administered in combination with two related glycopeptides, bleomycin A2 and bleomycin B2, which differ from bleomycin sulfate only in the moiety substituted on a terminal amine. The mechanism of action for this family of antineoplastic drugs appears to involve DNA binding and radical formation, which leads to the scission and fragmentation of DNA molecules.
|In vitro studies||Human marrow||The administration of bleomycin can induce chromosomal aberrations in human marrow cells, but the significance of this finding for fetal development is not known 1|
|Animal studies *||mice, rats||daily doses of bleomycin 2-8 times those used weekly in humans||The frequency of malformations was not greater than expected among the offspring of rats treated with daily doses of bleomycin 2-8 times those used once a week in humans 2. Fetal death and skeletal variants, as well as maternal toxicity, were seen with increasedfrequency at the higher doses. 2,3|
|rabbits||daily doses 1.2-5 times those used weekly in humans and higher doses||The frequency of malformations was not increased among the offspring of rabbits treated with bleomycin, but fetal death occurred with the higher doses 2,3.|
|mouse||Mouse experiments indicate that female germ cells are more sensitive to the cytotoxic and mutagenic effects of bleomycin than are those of males4.|
|Human studies||Case series||1st trim exposures||No epidemiological studies of congenital anomalies among the infants of women treated with bleomycin during pregnancy have been reported. No congenital anomalies were observed in one series among 23 children born to women who had been treated during pregnancy with cancer chemotherapeutic regimens that included bleomycin 5.Eleven of these women were treated during the first trimester.|
|Case reports||2nd and 3rd trim exposures||Isolated clinical reports are available on cases of non-Hodgkin?s lymphoma treated during the 2nd and 3rd trimesters of pregnancy with bleomycin and other antineoplastic agent 6-8. No fetal anomalies or chromosome changes were reported in these cases.|
|late exposures||Transient neonatal leukopenia and neutropenia were observed in a premature infant born to a woman who had been treated with bleomycin, etoposide, and cisplatin 7-10 days prior to delivery 9.|
- Bornstein RS et al: Cytogenic effects of bleomycin therapy in man. Cancer Res 31:2004-7, 1971.
- Thompson DJ et al: Effects of bleomycin (NSC-125066) on reproduction, pre- and postnatal development in the rat and on prenatal development in the rabbit. US NTIS, PB Rep, PB-261972, 1976.
- Nishimura H and Tanimura T: Clinical Aspects of the Teratogenicity of Drugs. Excerpta Medica, American Elsevier Publishing Co., NY, 1976.
- Sudman PD, Rutledge JC, Bishop JB, Generoso WM: Bleomycin:female-specific dominant lethal effects in mice. Mutat Res 296:143-56,1992.
- Aviles A, Diaz Maqueo JC, Talavera A, Guzman R, Garcia EL: Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am J Hematol 36:243-8, 1991.
- Ortega J: Multiple agent chemotherapy including bleomycin of non-Hodgkin's lymphoma during pregnancy. Cancer 40:2829-35, 1977.
- Falkson HC et al: Non-Hodgkin's lymphoma in pregnancy. Cancer 45:1679-82, 1980.
- Lowenthal RM et al: Normal infant after combination chemotherapy including tenoposide for Burkitt's lymphoma in pregnancy. Med Pediatr Oncol 10:165-9, 1982.
- Raffles A, Williams J, Costeloe K, Clark P: Transplacental effects of maternal cancer chemotherapy. Br J Obstet Gynaecol 96:1099-1100, 1989.