Antineoplastic
PREGNANCY RECOMMENDATION: Contraindicated—1st Trimester
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
The limited data suggest that chlorambucil is a human teratogen.
FETAL RISK SUMMARY
The use of the alkylating agent, chlorambucil, during pregnancy has resulted in both normal and deformed infants (1–7). Two reports observed unilateral agenesis of the left kidney and ureter in male fetuses following 1st trimester exposure to chlorambucil (3,4). Similar defects have been found in animals exposed to the drug (8). In a third case, a pregnant patient was treated with chlorambucil at the 10th week of gestation (5). A full-term infant was delivered, but died 3 days later of multiple cardiovascular anomalies. The fourth case involved a woman treated with 24 mg/day during weeks 3–4 (6). She aborted in the 1st trimester a fetus with a retinal defect. In a 2012 report, a woman with chronic lymphocytic leukemia was treated with chlorambucil 2 mg/day 3 times per week during the first 20 weeks of pregnancy (7). Because of preeclampsia, she had a cesarean section at 36 weeks’ gestation to give birth to a healthy 2235-g male infant who had normal growth and development at 3 months of age.
Chlorambucil is mutagenic as well as carcinogenic (9–13). These effects have not been reported in newborns following in utero exposure. Data from one review indicated that 40% of the infants exposed to anticancer drugs were of low birth weight (14). Long-term studies of growth and mental development in offspring exposed to chlorambucil during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (15).
Amenorrhea and reversible azoospermia with high doses have been reported (16–20). Long-term follow-up of menstrual and reproductive function in women treated with various antineoplastic agents was reported in 1988 (20). Only two of the 40 women studied, however, may have been exposed to chlorambucil (see Cyclophosphamide).
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).
BREASTFEEDING SUMMARY
No reports describing the use of chlorambucil during lactation have been located. Because of the potential for severe adverse effects in a nursing infant, women receiving this alkylating agent should not breastfeed.
References
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18.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.
19.Schilsky RL, Lewis BJ, Sherins RJ, Young RC. Gonadal dysfunction in patients receiving chemotherapy for cancer. Ann Intern Med 1980;93:109–14.
20.Gershenson DM. Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors. J Clin Oncol 1988;6:270–5.