Antineoplastic
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
Although the animal reproduction data suggest risk during organogenesis, the human pregnancy experience with vinorelbine is limited to 10 cases, all in the 2nd and 3rd trimesters. Transient anemia was observed in one infant and another had mild leukopenia and thrombocytopenia, but other antineoplastic agents were used in each case. The limited human data prevent a more complete assessment of the embryo–fetal risk. Avoiding the use of this agent in gestation, especially in the 1st trimester and/or close to delivery, is reasonable. However, if the mother’s condition requires this therapy and consent is given, vinorelbine should not be withheld because of pregnancy.
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 at one-third the human dose (HD) and in rabbits at one-fourth the HD have shown embryo and/or fetal toxicity (1). At maternal nontoxic doses, intrauterine growth restriction and delayed ossification were observed. Vinorelbine did not affect fertility when administered to rats at weekly doses that were one-third the HD or alternate-day doses that were 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 about 1/15th and 1/4th the HD, respectively, for 13 or 26 weeks (1).
It is not known if vinorelbine crosses the placenta to the fetus. The molecular weight (about 1079) suggests that placental transfer of the drug to the embryo or fetus would be inhibited, but probably not prevented.
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, 1 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. Vinorelbine, in combination with 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 liveborn infants (3).
A 34-year-old woman with a history of breast cancer presented at 15 weeks’ gestation with metastases to the spine, pelvis, and hips (4). She refused all antineoplastic therapy until about 19 weeks’. At that time, she was started on vinorelbine (25 mg/m2) but her condition continued to deteriorate. Therapy was changed to docetaxel (100 mg/m2) and methylprednisolone every 3 weeks. After three cycles, a planned cesarean section at 32 weeks’ delivered a normal, 1620-g female infant with Apgar scores of 8 and 9. The child was developing normally at 20 months of age (4).
Rapidly progressing nonsmall-cell lung cancer was diagnosed in a 31-year-old woman at 25 weeks’ gestation (5). One week later, she received vinorelbine (25 mg/m2) and cisplatin (100 mg/m2), but because her condition continued to worsen, a cesarean section was performed 4 days later to deliver a healthy male infant with Apgar scores of 7 and 8 at 1 and 5 minutes, respectively. Ten days after chemotherapy, a transient decrease in the infant’s white blood cell and platelet counts was observed but both resolved 3 weeks after birth (5).
A 26-year-old woman with breast cancer was treated with trastuzumab, paclitaxel, fluorouracil, epirubicin, and cyclophosphamide, followed by a left mastectomy and radiation therapy (6). Fourteen months later, in the 27th week of pregnancy, multiple hepatic metastases were detected. She was treated with trastuzumab (one dose of 4mg/kg, then 2 mg/kg every week) and vinorelbine (25 mg/m2 weekly for 3 weeks followed by a week of rest) until 34 weeks’ gestation. Oligohydramnios occurred during therapy that was most likely secondary to trastuzumab (see Trastuzumab). Because of decreased fetal movement, labor was induced at 34 weeks’ gestation and a healthy 2.6-kg male infant was delivered vaginally with Apgar scores of 9, 9, and 10. At 6 months of age, the infant was healthy and developing normally (6).
BREASTFEEDING 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 as seen in adults) in a nursing infant, women who require this agent should not breastfeed.
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.
4.De Santos M, Lucchese A, De Carolis S, Ferrazzani S, Caruso A. Metastatic breast cancer in pregnancy: first case of chemotherapy with docetaxel. Eur J Cancer Care (Engl) 2000;9:235–7.
5.Jänne PA, Rodriguez-Thompson D, Metcalf DR, Swanson SJ, Greisman HA, Wilkins-Haug L, Johnson BE. Chemotherapy for a patient with advanced nonsmall-cell lung cancer during pregnancy: a case report and a review of chemotherapy treatment during pregnancy. Oncology 2001;61:175–83.
6.Fanale MA, Uyei AR, Therialult RL, Adam K, Thompson RA. Treatment of metastatic breast cancer with trastuzumab and vinorelbine during pregnancy. Clin Breast Cancer 2005;6:354–6.