VINORELBINE

Fetal Risk Summary

Vinorelbine is a semisynthetic vinca alkaloid that is used in the treatment of cancer. It is related to two other vinca alkaloids, vinblastine and vincristine.

Reproduction studies in mice and rabbits at 9 mg/m2 (one-third the human dose [HD]) and 5.5 mg/m2 (one-fourth the HD) have shown embryo and/or fetal toxicity (1). At maternal nontoxic doses, intrauterine growth retardation and delayed ossification were observed. Vinorelbine did not affect fertility when administered to rats at 9 mg/m2 weekly doses (one-third the HD) or alternate-day doses of 4.2 mg/m2 (one-seventh the HD) before and during mating (1). The agent did reduce spermatogenesis and prostate/seminal vesicle secretion in male rats given biweekly doses of 2.1 mg/m2 and 7.2 mg/m2 (about one-fifteenth and one-fourth the HD, respectively) for 13 or 26 weeks (1).

It is not known if vinorelbine crosses the placenta to the fetus. The relatively high molecular weight (about 1079) suggests that placental transfer of the drug to the embryo or fetus would be inhibited.

In a brief 1997 report, three pregnant women with breast cancer were successfully treated with two or three courses of vinorelbine (20–30 mg/m2) and fluorouracil (500–750 mg/m2) at 24, 28, and 29 weeks' gestation, respectively (2). Delivery occurred at 34, 41, and 37 weeks' gestation, respectively. One patient also required six courses of epidoxorubicin and cyclophosphamide. Her infant developed transient anemia at 21 days of age that resolved spontaneously. No adverse effects were observed in the other two newborns. All three infants were developing normally at about 2–3 years of age (2).

A 1999 report from France described the outcomes of pregnancies in 20 women with breast cancer who were treated with antineoplastic agents (3). 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 (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 (3). Vinorelbine, in combination fluorouracil, was administered to four women at a mean dose of 37 mg/m2 (range 20–50 mg/m2) during the 2nd or 3rd trimesters. The outcomes were four surviving live-born infants (3).

Breast Feeding Summary

No reports describing the use of vinorelbine during lactation have been located. Because of the potential for severe toxicity (e.g., bone marrow depression) in a nursing infant, women who require this agent should avoid breast feeding. This precaution applies to all antineoplastic agents.

References

1. Product information. Navelbine. Glaxo Wellcome, 1999.
2. Cuvier C, Espie M, Extra JM, Marty M. Vinorelbine in pregnancy. Eur J Cancer 1997;33:168–9.
3. Giacalone PL, Laffargue F, Benos P. Chemotherapy for breast carcinoma during pregnancy. Cancer 1999;86:2266–72.