Antineoplastic
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
Streptozocin is teratogenic or embryotoxic in several animal species and possesses mutagenic and carcinogenic effects. The potential for human embryo–fetal injury is a concern, but because the animal reproduction data lacks dosage and time of exposure information and other data, the degree of risk is unknown. One report has described the use of this drug during the latter half of gestation without apparent fetal harm. Until additional data are forthcoming, streptozocin should be considered a potential human teratogen if exposure occurs during organogenesis.
FETAL RISK SUMMARY
Streptozocin (streptozotocin) is an alkylating antineoplastic that is obtained from Streptomyces achromogenes. This nitrosourea agent belongs to the same group as carmustine (BCNU) and lomustine (CCNU). Streptozocin is indicated for the treatment of metastatic islet cell carcinoma of the pancreas and also is used in other cancers. It is rapidly cleared from the plasma and is distributed to tissues, primarily the kidneys, liver, intestines, and pancreas (1,2). Streptozocin undergoes extensive metabolism and, although it does not cross the blood–brain barrier, its metabolites are found in the cerebrospinal fluid (CSF) (1).
Streptozocin is mutagenic in bacteria, plants, and mammalian cells and is carcinogenic (renal, hepatic, stomach, and pancreatic tumors) in various animal species such as mice, rats, and hamsters (2). The drug also is diabetogenic in laboratory animals (3).
Reproduction studies with streptozocin have been conducted in pregnant rats and rabbits. Although the doses and administration times were not specified, streptozocin was teratogenic (types of defects not specified) in rats and had abortifacient effects in rabbits (2). No mention was made of maternal toxicity in these studies.
Studies investigating the passage of streptozocin across the human placenta have not been located. The molecular weight (about 265) is low enough that exposure of the embryo or fetus should be expected. Moreover, in pregnant monkeys administered IV streptozocin, the agent appeared rapidly in the fetal circulation (2). However, the rapid clearance from the blood and the absence of the parent drug in the CSF suggest that the amount crossing the placenta, at least of unmetabolized drug, will be limited.
A 1984 report described a 21-year-old woman with diffuse histiocytic lymphoma treated before pregnancy with multiple courses of chemotherapy including cyclophosphamide, doxorubicin, vincristine, bleomycin, methotrexate, cytarabine, and etoposide, in addition to radiation therapy to the neck (4). Because of the failure of that therapy, she was changed to carmustine and procarbazine for 5 months before conception. The patient refused to terminate her pregnancy, and treatment with carmustine and procarbazine was continued during the first 24 weeks of pregnancy. Because of disease progression, her therapy was changed at 24 weeks’ gestation to three courses of streptozocin, 800 mg IV/day for 3 days every 4 weeks. The last course was administered 2 weeks before delivery at 35 weeks’ gestation. The normal-appearing male infant weighed 2.34 kg with a head circumference of 32.5 cm and a length of 51.5 cm. The Apgar scores were 7 and 9 at 1 and 5 minutes, respectively. Initial tests revealed normal hemoglobin, and white blood cell and platelet counts. All other clinical tests were within normal limits, including electrolytes, multiple chemistry, urinalysis, renal ultrasound, and chromosome studies (2).
BREASTFEEDING SUMMARY
No reports describing the use of streptozocin during human lactation have been located. The molecular weight (about 265) suggests that the drug will be excreted in breast milk. The effects of this exposure on a nursing infant are unknown. Because of the potential for serious toxicity, women receiving streptozocin should not nurse.
References
1.Parfitt K, ed. Martindale: The Complete Drug Reference. 32nd ed. London, UK: Pharmaceutical Press, 1999:562.
2.Product information. Zanosar. Pharmacia & Upjohn, 2000.
3.Schein PS, Winokur SH. Immunosuppressive and cytotoxic chemotherapy: long-term complications. Ann Intern Med 1975;82:84–95.
4.Schapira DV, Chudley AE. Successful pregnancy following continuous treatment with combination chemotherapy before conception and throughout pregnancy. Cancer 1984;54:800–3.