VINCRISTINE

Fetal Risk Summary

Vincristine is an antimitotic antineoplastic agent. The drug is embryocidal and teratogenic in mice, hamsters, and monkeys (1). Doses that produced these effects were nontoxic to the pregnant animal.

The use of vincristine has been described in at least 36 pregnancies (1 with twins), 9 during the 1st trimester (2,3,4,5,6,7,8,9,10,11,12, 13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30 and 31).

A mother with Hodgkin's disease treated with vincristine, vinblastine, and procarbazine in the 1st trimester (3 weeks after the last menstrual period) delivered a 1900-g male infant at about 37 weeks' gestation (10). Neonatal death occurred because of respiratory distress syndrome. At autopsy, a small secundum atrial septal defect was found. In a Hodgkin's case treated with vincristine, mechlorethamine, and procarbazine during the 1st trimester, the electively aborted fetus had malformed kidneys (markedly reduced size and malpositioned) (16). Other adverse fetal outcomes observed following vincristine use include a 1000-g male infant born with pancytopenia who was exposed to six different antineoplastic agents in the 3rd trimester (2) and transient severe bone marrow hypoplasia in another newborn that was most likely caused by mercaptopurine (19). Intrauterine fetal death occurred in a 1200-g female fetus 36 hours after maternal treatment with vincristine, doxorubicin, and prednisone for diffuse, undifferentiated lymphoma of T-cell origin at 31 weeks' gestation (22). The fetus was macerated, but no other abnormalities were observed at autopsy. In another case, a 34-year-old woman with acute lymphoblastic leukemia was treated with multiple antineoplastic agents from 22 weeks' gestation until delivery of a healthy female infant 18 weeks later (25). Vincristine was administered 4 times between 22–25 weeks' gestation. Chromosomal analysis of the newborn revealed a normal karyotype (46,XX) but with gaps and a ring chromosome. The clinical significance of these findings is unknown, but because these abnormalities may persist for several years, the potential existed for an increased risk of cancer, as well as for a risk of genetic damage in the next generation (25).

A 1999 report from France described the outcomes of pregnancies in 20 women with breast cancer who were treated with antineoplastic agents (31). The first cycle of chemotherapy occurred at a mean gestational age of 26 weeks with delivery occurring at a mean 34.7 weeks. A total of 38 cycles were administered during pregnancy with a median of two cycles per woman. None of the women received radiation therapy during pregnancy. The pregnancy outcomes included two spontaneous abortions (SABs) (both exposed in the 1st trimester), one intrauterine death (exposed in the 2nd trimester), and 17 live births, one of whom died at 8 days of age without apparent cause. The 16 surviving children were developing normally at a mean follow-up of 42.3 months (31). Vincristine (V), in combination with doxorubicin (D), epirubicin (E), and/or methotrexate (M), was administered to two women at a mean dose of 2 mg/m2. The outcomes were one SAB (VEM; exposed at 6 weeks' gestation) and one surviving liveborn infant (exposed to VD in the 2nd trimester) (31).

Data from one review indicated that 40% of the infants exposed to anticancer drugs were of low birth weight (32). This finding was not related to the timing of exposure. Long-term studies of growth and mental development in offspring exposed to these drugs during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (33). However, individual infants have been evaluated for periods ranging from a few weeks up to 7 years and all have had normal growth and development (17,18,19 and 20, 22,23 and 24,26,27,29).

Vincristine, in combination with other antineoplastic agents, may produce gonadal dysfunction in men and women (34,35,36,37,38,39,40 and 41). Alkylating agents are the most frequent cause of this problem (38). Ovarian and testicular function may return to normal with successful pregnancies possible, depending on the patient's age at time of treatment and the total dose of chemotherapy received (34). In a 1989 case report, a woman with an immature teratoma of the ovary was treated with conservative surgery and chemotherapy consisting of six courses of vincristine, dactinomycin, and cyclophosphamide (42). She conceived 20 months after her last chemotherapy and eventually delivered a normal 3340-g male infant. The long-term effects of combination chemotherapy on menstrual and reproductive function have been described in a 1988 report (43). Twenty-nine of 40 women treated for malignant ovarian germ cell tumors received vincristine. The results of this study are discussed in the monograph for cyclophosphamide (see Cyclophosphamide).

In 436 long-term survivors treated with chemotherapy between 1958 and 1978 for gestational trophoblastic tumors, 132 (30%) received vincristine in combination with other antineoplastic agents (44). The mean duration of chemotherapy was 4 months with a mean interval from completion of therapy to the first pregnancy of 2.7 years. Conception occurred within 1 year of therapy completion in 45 women (antineoplastic agents used in these women were not specified), resulting in 31 live births, 1 anencephalic stillbirth, 7 SABs, and 6 elective abortions. Of the 132 women treated with vincristine, 37 (28%) had at least one live birth (numbers in parentheses refer to mean/maximum vincristine dose in milligrams) (7.4/17.0), 8 (6%) had no live births (7.1/22.0), 4 (3%) failed to conceive (7.3/18.0), and 83 (63%) did not try to conceive (11.3/46.0). The average ages at the end of treatment in the four groups were 24.9, 24.4, 24.4, and 31.5 years, respectively. Congenital abnormalities noted in the total group (368 conceptions) were two cases of anencephaly, and one case each of spina bifida, tetralogy of Fallot, talipes equinovarus, collapsed lung, umbilical hernia, desquamative fibrosing alveolitis, asymptomatic heart murmur, and mental retardation. Another child had tachycardia but developed normally after treatment. One case of sudden infant death syndrome occurred in a female infant at 4 weeks of age. None of these outcomes differed statistically from that expected in a normal population (44).

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

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