BLEOMYCIN

Fetal Risk Summary

Bleomycin is an antineoplastic agent whose mechanism of action is thought to be inhibition of DNA synthesis and lesser inhibition of RNA and protein synthesis (1). The drug is teratogenic in rats. Skeletal malformations, shortened innominate artery, and hydroureter were observed at an intraperitoneal dose of 1.5 mg/kg/day (about 1.6 times the recommended human dose [RHD] on a unit/m2 basis given on days 6–15 of gestation (1). An IV dose of 1.2 mg/kg/day (about 2.4 times the RHD) administered to rabbits on gestational days 6–18 resulted in abortions, but no teratogenic effects.

No reports linking the use of bleomycin with congenital defects in humans have been located. Chromosomal aberrations in human marrow cells have been reported, but the significance to the fetus is unknown (2). Two separate cases of non-Hodgkin's lymphoma in pregnancy were treated during the 2nd and 3rd trimesters with bleomycin and other antineoplastic agents (3,4). Normal infants without anomalies or chromosomal changes were delivered. In another case, a 21-year-old woman with a Ewing's sarcoma of the pelvis was treated with bleomycin and four other antineoplastic agents at approximately 25 weeks' gestation (5). Nine weeks later, recurrence of tumor growth necessitated delivery of the normal infant by cesarean section to allow for more definitive treatment of the tumor. The child was reported to be developing normally at 4 years of age.

A 1989 case report described the effect of maternal chemotherapy on a premature newborn delivered at approximately 27 weeks' gestation (6). The mother was treated with bleomycin (30 mg), etoposide (165 mg), and cisplatin (55 mg) (all given daily for 3 days), 1 week before delivery, for an unknown primary cancer with metastases to the eye and liver. The mother developed profound neutropenia just before delivery. On the 3rd day after delivery, the 1190-g female infant also developed a profound leukopenia with neutropenia, 10 days after in utero exposure to the antineoplastic agents. The condition resolved after 10 days. At 10 days of age, the infant began losing her scalp hair and experienced a rapid loss of lanugo (6). Etoposide was thought to be the most likely cause of the neutropenia and the alopecia (6). By 12 weeks of age, substantial hair regrowth had occurred, and at 1 year follow-up, the child was developing normally except for moderate bilateral hearing loss. The investigators could not determine whether the sensorineural deafness was caused by the maternal and/or neonatal gentamicin therapy, or by the maternal cisplatin chemotherapy (6).

A 25-year-old woman underwent surgery at 25 weeks' gestation for an endodermal sinus tumor of the ovary (7). A chemotherapy cycle consisting of bleomycin (50 mg), cisplatin (75 mg/m2), and vinblastine (0.25 mg/kg) was started 9 days later. Approximately 3 weeks later she received a second cycle of therapy. A normal, healthy 1900-g male infant was delivered by scheduled cesarean section at 32 weeks' gestation. The infant was alive and growing normally at the time of the report.

Combination chemotherapy with bleomycin was used for teratoma of the testis in two men (8). In both cases, recovery of spermatogenesis with apparently successful fertilization occurred, but the possibility of alternate paternity could not be excluded.

The long-term effects of combination chemotherapy on menstrual and reproductive function were described in a 1988 report (9). Only 7 of 40 women treated for malignant ovarian germ cell tumors received bleomycin. The results of this study are discussed in the monograph for cyclophosphamide (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).

Breast Feeding Summary

No data are available.

References

1. Product information. Blenoxane. Bristol-Myers Squibb Oncology/Immunology Division, 2000.
2. Bornstein RS, Hungerford DA, Haller G, Engstrom PF, Yarbro JW. Cytogenic effects of bleomycin therapy in man. Cancer Res 1971;31:2004–7.
3. Ortega J. Multiple agent chemotherapy including bleomycin of non-Hodgkin's lymphoma during pregnancy. Cancer 1977;40:2829–35.
4. Falkson HC, Simson IW, Falkson G. Non-Hodgkin's lymphoma in pregnancy. Cancer 1980;45: 1679–82.
5. Haerr RW, Pratt AT. Multiagent chemotherapy for sarcoma diagnosed during pregnancy. Cancer 1985;56:1028–33.
6. Raffles A, Williams J, Costeloe K, Clark P. Transplacental effects of maternal cancer chemotherapy: case report. Br J Obstet Gynaecol 1989;96:1099–1100.
7. Malone JM, Gershenson DM, Creasy RK, Kavanagh JJ, Silva EG, Stringer CA. Endodermal sinus tumor of the ovary associated with pregnancy. Obstet Gynecol 1986;68(Suppl):86S–9S.
8. Rubery ED. Return of fertility after curative chemotherapy for disseminated teratoma of testis. Lancet 1983;1:186.
9. Gershenson DM. Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors. J Clin Oncol 1988;6:270–5.