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Motherisk Update 2014
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Current Studies at Motherisk
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Cancer in Pregnancy: 5-Fluorouracil
5-Fluorouracil (5-FU) is a pyrimidine analog antineoplastic agent that acts by interfering with the synthesis of DNA and RNA.
|Animal studies *||Rats||doses of 12 to 40 mg/kg||Fetal anemia, defects of the nervous system , palate and skeleton 1,2,3|
|pharmacokinetic studies pregnant rats||5-FU is poorly eliminated by exposed fetus, and can produce fetotoxicity at doses that are nontoxic to the dam 4|
|Mice, rabbits, guinea pigs and hamsters||Hindfoot anomalies, cleft palate, microphtalmia and omphalocele 5|
|Monkeys||Rib and vertebral anomalies, intrauterine growth retardation and fetal death 6,7|
|Human studies||Case series||No epidemiological studies of congenital anomalies among infants born to pregnant women treated with fluorouracil have been reported. In a case series of 21 pregnant patients with exposure to cancer chemotherapy, 3 were exposed to combination regimens including 5-FU. Two exposures were during the first trimester and one ended as a spontaneous abortion and another was a normal live baby. The third exposure occurred during the third trimester and the baby was alive, without malformations but showing intrauterine growth retardation 8|
|Case reports||1st trim exposure||There are only a few case reports of 5-FU systemic exposure during pregnancy.|
|11 - 12 wks of pregnancy; exposed also to 5 rad of irradiation||Therapeutic abortion at 16 weeks. The fetus had multiple defects including bilateral radial aplasia, absent thumbs, oligodactyly, hypoplasia of lungs, aorta, thymus and bile duct, and aplasia of the esophagus, duodenum and ureters. In this case, 5-FU probably is not related with the malformations because at the time of exposure most of the organogenesis has already ended 9|
|2nd and 3rd trim||5-FU was
administered in a patient in high doses over 5 months during the 2nd
and 3rd trimester. The baby was small but healthy 10.
A normal baby delivered by cesarean section at 35 weeks after exposure since the 13th week to 5-FU, cyclophosphamide, and doxorubicin. Normal growth and development at 24 months of age 11.
|3rd trim||A newborn exposed to 5-FU during the third trimester was not malformed but had transient toxicity signs with cyanosis and jerking extremities during the neonatal period 12|
- Chaube S, Murphy ML: The teratogenic effects of the recent drugs active in cancer chemotherapy, in Whoollam DHM (Ed) : Advances inTeratology, Vol. 3, NY, Academic Press, 1968, pp. 181-237.
- Shuey DL, Zucker RM, Elstein KH and Rogers JM: Fetal anemia following maternal exposure to 5-fluorouracil in the rat. Teratology49:311-319, 1994.
- Shuey DL, Lau C, Logsdon TR et al: Biologically based dose-response modeling in developmental toxicology: biochemical and cellular sequelae of 5-fluorouracil exposure in the development in the rat.Toxicol Appl Pharmacol 126: 129-144, 1994.
- Boike GM et al: Chemotherapy in a pregnant rat model.Gynecol Oncol 34: 191-4, 1989.
- Dagg , CP: Sensitive stages for the production of developmental abnormalities in mice with 5-fluorouracil. Am J Anat 106: 89-96, 1960.
- Wilson, JG: Use of rhesus monkeys in the teratological studies. FedProc 30:104-109, 1972.
- Wilson, JG: Abnormalities of intrauterine development in nonhuman primates. Acta Endocrinol 71 (Suppl 166): 261-292, 1972.
- Zelmlickis D, Lishner M, Degendorfer P et al: Fetal outcome after in utero exposure to cancer chemoterapy. Arch Intern Med 152: 573-6, 1992.
- Stephens TD et al: Multiple congenital anomalies in a fetus exposed to 5-fluorouracil during the first trimester. Am J Obstet Gynecol 137: 747-9,1980.
- Dreicer R, Love RR: High total dose 5-fluorouracil treatment during pregnancy. Wis Med J 90: 582-3, 1991.
- Turchi JJ & Villasis C. Anthraciclines in the treatment of malignancy in pregnancy. Cancer, 61: 435-440, 1988.
- Stadler HE, Knowles J: Fluorouracil in pregnancy: effect on the neonate. J Am Med Assoc 217: 214-5, 1971.