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Current Studies at Motherisk
The Safety of Diclectin in Breastfeeding
Neurodevelopment of Children Exposed in-Utero to Chemotherapy for Maternal Breast Cancer (Dr. I Nulman)
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Cancer in Pregnancy: Vinblastine
Vinblastine is an alkaloid derived from the periwinkle plant used for the treatment of neoplastic disease. It interferes with the miotic cells arresting the metaphases. It is related to vincristine.
|Animal studies *||Hamsters1||0.25 mg/kg intravenously on the 8th gestational day||Fetal death . Increased incidence of skeletal and eye defects, spina bifida and exencephaly.|
|Mice 2||100 - 1000 times the doses used in humans||Increased frequency of fetal death|
|Rats 3||1 - 5 times the doses used in humans||Increased incidence of eye defects, microcephaly, neural tube defects and midfacial defects. Many arrested metaphases observed in the treated embryos.|
|Rabbits 4||Doses similar to those used in humans||Fetal death|
|Human studies||Case reports||1st trim exposure||More than 15 cases of first trimester exposure to vinblastine have been reported. Malformations described were:|
|Combination with: procarbazine + nitrogen mustard||1. A spontaneously aborted male fetus at 24 weeks of gestation, with only four toes in both feet and partial syndactyly 5.|
|Combination with: vincristine + procarbazine||2. A 1900g
male infant delivered at 37 weeks of pregnancy. He died after
respiratory distress syndrome and at autopsy a small secundum atrial
septal defect was observed 6.
OBS: Two other malformed children were reported in a case series described below 7.
|2nd and 3rd trim exposures||There are more than 10 cases exposed during the 2nd or 3rd trimester of pregnancy to vinblastine with normal outcomes 8.|
|Case series||No epidemiological studies of congenital anomalies among the infants of women treated with vinblastine during pregnancy were found. A number of case series which included exposures during the first trimester suggest that the risk for teratogenicity is small:
1. No congenital anomalies were observed in one series among 10 children born to women treated during pregnancy with cancer chemotherapeutic regimens that included vinblastine. Four of these women were treated during the first trimester 9. Their growth, intellectual development and cytogenetic analysis were normal in ages ranging from 3 - 19 years at the time of the follow-up.
2. In a series of 26 pregnancies of women receiving chemotherapy for cancer there was one baby with hydrocephalus exposed intra-utero to vinblastine at week 3. Another baby presented cleft lip and palate and was exposed to lomustine, vincristine, prednisone and procarbazine from week 1-6 and to vinblastine from week 9 to term 7.
|Pre-pregnancy||A study of 445 long-term survivors treated with chemoterapy for gestational tumors, including vinblastine, did not show any increased incidence of congenital malformation in their children 10.
A study performed in children fathered by 25 patients treated for testicular cancer including vinblastine did not show any increase in the rate of congenital malformations 11.
- Ferm VH: Congenital malformations in hamster embryos after treatment with vinblastine and vincristine. Science 141:426,1963.
- Joneja MG, LeLiever WC: Effect of vinblastine and podophyllin on DBA mouse fetuses. Toxicol Appl Pharmacol 27:408-414, 1974.
- Demyer W: Vinblastine-induced malformations of face and nervous system in two rat strains. Neurology 14:806-8, 1964.
- Morris JM et al: Compounds interfering with ovum implantation and development. I. Alkaloids and antimetabolites. Fertil Steril18:7-17,1967.
- Garrett MJ: Teratogenic effects of combination chemotherapy. Ann Intern Med 80:667, 1974.
- Thomas PRM, Peckham MJ: The investigation and management of Hodgkin's disease in the pregnant patient. Cancer 38:1443-51, 1976
- Mulvihill JJ et al: Pregnancy outcome in cancer patients. Cancer 60:1143-50, 1987.
- Doll DC, Ringenberg QS & Yarbro JW Antineoplastic agents and pregnancy. Semin Oncol. 16(5): 337-346, 1989.
- Aviles et al: Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am JHematol 36:243-8, 1991.
- Rustin GJS et al: Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumors. Br Med J 288:103-106, 1984.
- Senturia YD et al: Children fathered by men treated for testicular cancer. Lancet ii:766-769, 1985.