VINBLASTINE

Fetal Risk Summary

Vinblastine is an antimitotic antineoplastic agent. The drug is embryocidal and teratogenic in laboratory animals (no details provided) (1).

The drug has been used in pregnancy, including the 1st trimester, without producing malformations (2,3,4,5,6,7,8,9 and 10). Two cases of malformed infants have been reported following 1st trimester exposure to vinblastine (10,11). In 1974, a case of a 27-year-old woman with Hodgkin's disease who was given vinblastine, mechlorethamine, and procarbazine during the 1st trimester was described (11). At 24 weeks' gestation, she spontaneously aborted a male fetus with oligodactyly of both feet with webbing of the third and fourth toes. These defects were attributed to mechlor-ethamine therapy. A mother with Hodgkin's disease treated with vinblastine, vincristine, and procarbazine in the 1st trimester (3 weeks after the last menstrual period) delivered a 1900-g male infant at about 37 weeks of gestation (12). The newborn developed fatal respiratory distress syndrome. At autopsy, a small secundum atrial septal defect was found.

Vinblastine in combination with other antineoplastic agents may produce gonadal dysfunction in men and women (13,14,15 and 16). Alkylating agents are the most frequent cause of this problem (15). Although total aspermia may result, return of fertility has apparently been documented in at least two cases (16). Ovarian function may return to normal with successful pregnancies possible, depending on the patient's age at the time of therapy and the total dose of chemotherapy received (14,17). The long-term effects of combination chemotherapy on menstrual and reproductive function were described in a 1988 report (18). Only 5 of 40 women treated for malignant ovarian germ cell tumors received vinblastine. The results of this study are discussed in the monograph for cyclophosphamide (see Cyclophosphamide).

In 436 long-term survivors treated with chemotherapy for gestational trophoblastic tumors between 1958 and 1978, 11 (2.5%) received vinblastine as part of their treatment regimens (19). Of the 11 women, 2 (18%) had at least one live birth (mean and maximum vinblastine dose 20 mg), and 9 (82%) did not try to conceive (mean dose 37 mg, maximum dose 80 mg). Additional details, including congenital anomalies observed, are described in the monograph for vincristine (see Vincristine).

Data from one review indicated that 40% of infants exposed to anticancer drugs were of low birth weight (20). This finding was not related to the timing of exposure. Long-term studies of growth and mental development in offspring exposed to vinblastine during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (21). However, two children exposed throughout gestation, beginning with the 3rd–4th week of gestation, were normal at 2 and 5 years of age, respectively (10).

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 data are available.

References

1. Product information. Velban. Eli Lilly, 2000.
2. Armstrong JG, Dyke RW, Fouts PJ, Jansen CJ. Delivery of a normal infant during the course of oral vinblastine sulfate therapy for Hodgkin's disease. Ann Intern Med 1964;61:106–7.
3. Rosenzweig AI, Crews QE Jr, Hopwood HG. Vinblastine sulfate in Hodgkin's disease in pregnancy. Ann Intern Med 1964;61:108–12.
4. Lacher MJ. Use of vinblastine sulfate to treat Hodgkin's disease during pregnancy. Ann Intern Med 1964;61:113–5.
5. Lacher MJ, Geller W. Cyclophosphamide and vinblastine sulfate in Hodgkin's disease during pregnancy. JAMA 1966;195:192–4.
6. Nordlund JJ, DeVita VT Jr, Carbone PP. Severe vinblastine-induced leukopenia during late pregnancy with delivery of a normal infant. Ann Intern Med 1968;69:581–2.
7. Goguei A. Hodgkin's disease and pregnancy. Nouv Presse Med 1970;78:1507–10.
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9. Nisce LZ, Tome MA, He S, Lee BJ III, Kutcher GJ. Management of coexisting Hodgkin's disease and pregnancy. Am J Clin Oncol 1986;9:146–51.
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11. Garrett MJ. Teratogenic effects of combination chemotherapy. Ann Intern Med 1974;80:667.
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13. Morgenfeld MC, Goldberg V, Parisier H, Bugnard SC, Bur GE. Ovarian lesions due to cytostatic agents during the treatment of Hodgkin's disease. Surg Gynecol Obstet 1972;134:826–8.
14. Ross GT. Congenital anomalies among children born of mothers receiving chemotherapy for gestational trophoblastic neoplasms. Cancer 1976;37:1043–7.
15. Schilsky RL, Lewis BJ, Sherins RJ, Young RC. Gonadal dysfunction in patients receiving chemotherapy for cancer. Ann Intern Med 1980;93:109–14.
16. Rubery ED. Return of fertility after curative chemotherapy for disseminated teratoma of testis. Lancet 1983;1:186.
17. Shalet SM, Vaughan Williams CA, Whitehead E. Pregnancy after chemotherapy induced ovarian failure. Br Med J 1985;290:898.
18. Gershenson DM. Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors. J Clin Oncol 1988;6:270–5.
19. Rustin GJS, Booth M, Dent J, Salt S, Rustin F, Bagshawe KD. Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours. Br Med J 1984;288:103–6.
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21. Dobbing J. Pregnancy and leukaemia. Lancet 1977;1:1155.