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Cancer in Pregnancy: Doxorubicin

Doxorubicin is an antineoplastic antibiotic which may act by forming a stable complex with DNA and interfering with the synthesis of nucleic acids.

Setting Treatment Outcomes
In vitro studies chicks Doxorubicin produced increased malformations when tested in chicks 1. Doxorubicin exerts cardiac toxicity in postnatal life and embryonic chick cardiac myocytes take up the drug avidly in culture 2.
Species studied
Animal studies * mice, rats, mouse, rabbits up to 1.5 mg/kg/day Birth defects produced using clinically relevant doses (2 mg/kg) in the rat but not in the mouse or rabbit 3-5. Renal impairment produced in offspring of pregnant rats with up to 1.5 mg/kg/day 6.
Study Design
Human studies Cardiac dysfunction in infants exposed antenatally to doxorubicin has not been described.
pharmacokinetic study It has not been determined how well doxorubicin crosses the placenta; however, the drug has been detected in placental, cord, and fetal tissues 7.
Case reports 1st trimester exposure There have been several reports in humans of doxorubicin administration during pregnancy or just prior to conception, including ten cases during the first trimester 8-22. No adverse pregnancy outcomes were associated with the drug during 9 of the reported pregnancies.
1st trimester exposure
325 mg (total) Combination with: cyclophosphamide
2.1 g (total) with cobalt
Administration of doxorubicin 325 mg (total) and cyclophosphamide 2.1 g (total) with cobalt during the first trimester of pregnancy resulted in birth of a small neonate with imperforate anus and rectovaginal fistula which was responsive to surgery. Findings from chromosomal analyses were normal. The authors suggest that cytotoxic drug therapy during the first trimester of pregnancy is associated with a very small risk of malformations 15.
Case-control study Occupational exposure A retrospective study using a computerized occupation registry and mailed questionnaires suggested an association between occupational exposure of pregnant nurses to antineoplastic agents (including doxorubicin) and fetal loss. One analysis of data suggested the odds ratio for exposure to doxorubicin in association with fetal loss might be as high as 3.96 24. While this study is provocative, its design does not permit conclusions concerning occupational or therapeutic exposure to doxorubicin and adverse pregnancy outcome.
Breast feeding Case report Based on a single analysis in one lactating mother, the amount of doxorubicin excreted in breast milk appears to be small 25.
The amount of doxorubicin that a suckling infant would ingest in a feed is at maximum 0.5% of the weight-adjusted maternal single dose and in a day is at maximum 2.4% of the weight-adjusted maternal daily dose 26.
* - None of the animal studies reported in this table were conducted at The Hospital for Sick Children, Toronto, or by Motherisk.

References

  1. Zirvi KA et al: Embryotoxic effects of doxorubicin and N-trifluroacetyladriamycin-14-valerate (AD-32). Teratology 31:247-52, 1985.
  2. Lewis W et al: Compartmentalization of adriamycin and daunomycinin cultured chick cardiac myocytes. Effects on synthesis of contractile and cytoplasmic proteins. Circ Res 53:352-62, 1983.
  3. Thompson DJ et al: Teratogenicity of adriamycin and daunomycin in the rat and rabbit. Teratology 17:151-8, 1978.
  4. Oguro T et al: Toxicological studies on adriamycin-HCl. 4. Teratological study. Yakubutsu Ryoho 6:1152-64, 1973.
  5. Fantel AG et al: The embryotoxicity of adriamycin in rat embryos in vitro. Toxicol Appl Pharmacol 80:155-65, 1985.
  6. Kavlock RJ et al: Renal functional teratogenesis resulting from adriamycin exposure. Teratology 33:213-20, 1986.
  7. Karp GI et al: Doxorubicin in pregnancy: possible transplacental passage. Cancer Treat Rep 67:773-7, 1983.
  8. Dara P et al: Successful pregnancy during therapy for acute leukemia. Cancer 47:845-6, 1981.
  9. Garcia V et al: Doxorubicin in the first trimester of pregnancy. Ann Intern Med 94:547, 1981.
  10. Garcia V et al: Adriamycin and pregnancy. Sangre (Barcelona)26:129, 1981.
  11. Garg A, Kochupillai V: Non-Hodgkin's lymphoma in pregnancy. SouthMed J 78:1263-4, 1985.
  12. Gililland J, Weinstein L: The effects of cancer chemotherapeutic agents on the developing fetus. Obstet Gynecol Surv 38:6-13, 1983.
  13. Khursid M, Saleem M: Acute leukemia in pregnancy. Lancet 2:534-5, 1978.
  14. Lowenthal RM et al: Normal infant after combination chemotherapy including teniposide for Burkitt's lymphoma in pregnancy. Med Pediatr Oncol 10:165-9, 1982.
  15. Murray CL et al: Multimodal cancer therapy for breast cancer in the first trimester of pregnancy. A case report. JAMA 252:2607-8, 1984.
  16. Newcomb M et al: Acute leukemia in pregnancy: successful delivery after cytarabine and doxorubicin. J Am Med Assoc 239:2691-2, 1978.
  17. Pizzuto J et al: Treatment of acute leukemia during pregnancy: presentation of nine cases. Cancer Treat Rep 64:679-83, 1980.
  18. Roboz J et al: Does doxorubicin cross the placenta? Lancet 2:1382-3, 1979.
  19. Tobias JS, Bloom HJG: Doxorubicin in pregnancy. Lancet 1:776,1980.
  20. Webb GA: The use of hyperalimentation and chemotherapy in pregnancy: A case report. Am J Obstet Gynecol 137:263-6, 1980.
  21. Rustin GJS et al: Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours. Br Med J 288:103-6, 1984.
  22. AvilesA, Diaz-Maqueo JC, Talavera A, Guzman R, Garcia EL: Growthand development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am J Hematol 36: 243-8,1991.
  23. Lewis W et al: Compartmentalization of adriamycin and daunomycinin cultured chick cardiac myocytes. Effects on synthesis of contractile and cytoplasmic proteins. Circ Res 53:352-62, 1983.
  24. Selevan SG et al: A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med 313:1173-8,1985.
  25. Egan PC, Costanza ME, Dodion P, Egorin MJ, Bachur NR: Doxorubicin and cisplatin excretion into human milk. Cancer Treat Rep 69:1387- 9,1985.
  26. Bennet PN (ed).: Drugs and Human Lactation 2nd ED. Elsevier, Amsterdam, 1996, pp. 276-7.
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The information on this website is not intended as a substitute for the advice and care of your doctor or other health-care provider. Always consult your doctor if you have any questions about exposures during pregnancy and before you take any medications.

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