Antineoplastic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest High Risk
BREASTFEEDING RECOMMENDATION: Hold Breastfeeding
PREGNANCY SUMMARY
No reports describing the use of mitomycin in human pregnancy have been located. Although the doses were not compared with the human dose in terms of BSA or AUC, the drug was teratogenic or embryolethal in three animal species. If the drug is indicated in a pregnant woman, avoidance of the 1st trimester should be considered.
FETAL RISK SUMMARY
Mitomycin (mitomycin-C) is an antibiotic with antitumor activity isolated from Streptomyces caespitosus. It is in the same antineoplastic subclass of antibiotics as bleomycin and dactinomycin. Mitomycin is indicated in the therapy of disseminated adenocarcinoma of the stomach and pancreas in proven combinations with other approved chemotherapeutic agents and as palliative treatment when other modalities have failed. It is given as a single IV dose at 6–8-week intervals. The drug is primarily metabolized in the liver, but metabolism occurs in other tissues as well. However, metabolic pathways are saturated at relatively low doses. After a 30-mg IV bolus injection, the serum half-life was 17 minutes (1).
A number of reproduction studies in mice, rats, and dogs have been cited by Shepard and Lemire (2) and Schardein (3). Mitomycin caused either congenital malformations or embryolethality in these species when given during pregnancy (2,3). The studies specified doses based on weight, but apparently did compare them with the human dose based on BSA or AUC.
Mitomycin was carcinogenic in male rats and female mice. At doses approximating the recommended human clinical dose (assumed to be based on body weight), the tumor incidence in these species was increased by >100% and >50%, respectively. Assays for mutagenicity and tests for impaired fertility have not been conducted (1).
It is not known if mitomycin crosses the human placenta. The molecular weight (about 334) and the high lipid solubility suggest that it will, but the short serum half-life will limit the embryo–fetal exposure.
A 28-year-old nulliparous woman with squamous cell carcinoma of the uterine cervix was treated with four courses of low-dose mitomycin, cisplatin, bleomycin, and vincristine (4). The therapy produced a complete response. Two years later, she became pregnant and gave birth to a healthy infant.
BREASTFEEDING SUMMARY
No reports describing the use of mitomycin during human lactation have been located. The molecular weight (about 334) and the high lipid solubility suggest that it will be excreted into breast milk, but the short serum half-life (17 minutes) will limit the amount in milk. Because the drug is given as a single IV dose at 6–8-week intervals, pumping and dumping for a few hours after a dose should prevent exposure of a nursing infant.
References
1.Product information. Mitomycin For Injection, USP. Bedford Laboratories, 2000.
2.Shepard TH, Lemire RJ. Catalog of Teratogenic Agents. 12th ed. Baltimore: The Johns Hopkins University Press, 2007:297.
3.Schardein JL. Chemically Induced Birth Defects. 3rd ed. New York, NY: Marcel Dekker, 2000:567, 574.
4.Kobayashi Y, Aklyama F, Hasumi K. A case of successful pregnancy after treatment of invasive cervical cancer with systemic chemotherapy and conization. Gynecol Oncol 2006;100:213–5.