Streptozocin is a unique antineoplastic agent used to treat metastatic pancreatic islet cell carcinoma. Streptozocin has been associated with a high rate of serum enzyme elevation during therapy and to rare instances of severe, clinically apparent acute liver injury.


Streptozocin (strep" toe zoe' sin), which was formerly known as streptotozocin, is an antineoplastic antibiotic isolated initially from Streptomyces achromogenes. Structurally, streptozocin is a methylnitrosourea attached to a single molecule of glucosamine and acts as an alkylating agent causing DNA damage and interfering with synthesis. Streptozocin has high affinity for the cell surface glucose transporter GLUT 2 which is highly expressed on beta cells of the islets of Langerhans. As a consequence, streptozocin has differential toxicity to beta cells. In animal models, streptozocin caused loss of pancreatic islet cells, resulting in a decrease in serum insulin and diabetes. Used initially as a means of creating an animal model of type 1 diabetes, streptozocin was later used clinically to treat insulin-secreting islet cell tumors. It was tried, but had little effect in other malignancies. Streptozocin was approved for use in the chemotherapy of metastatic pancreatic islet cell carcinoma in the United States in 1982 and is still used, but largely in combination with other chemotherapeutic agents such as doxorubicin and fluorouracil. In addition, it has been used off label to treat other neuroendocrine neoplasms. Streptozocin is available as a powder for reconstitution in 1 gram vials under the brand name Zanosar. The typical dose is 500 mg/m2 daily for 5 days every 6 weeks or as 1 gram once weekly intravenously until a remission is achieved or significant toxicity intervenes. Common side effects of streptozocin therapy are nausea, vomiting, diarrhea, abdominal discomfort and local infusion site reactions. These immediate reactions can be followed by renal dysfunction (proteinuria, proximal tubular injury, phosphaturia, acute renal failure), bone marrow suppression (anemia, neutropenia) and hepatotoxicity.


Serum aminotransferase elevations occur in up to two-thirds of patients treated with streptozocin, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. Hepatotoxicity is more common with daily dosing and high doses of streptozocin, but with higher doses renal and hematologic toxicities usually overshadow hepatic injury. There have been two reports of rapidly progressive and fatal acute liver failure in patients treated with streptozocin. In one instance, no other chemotherapy was given, in another fluorouracil was coadministered and the patient presented with fever, anuria, acute hepatitis [ALT 1280, bilirubin 11.9, prothrombin index 10%, eosinophils 2600/ µL] at the end of a 5 day course of treatment. In contrast, there have been no individual published case reports of self-limited clinically apparent liver injury attributed to streptozocin, but it has had limited use, as pancreatic islet cell carcinoma and neuroendocrine tumors are rare.

Likelihood score: D (possible cause of clinically apparent liver injury).

Mechanism of Injury

Like the renal and bone marrow toxicity, the hepatic injury from streptozocin is likely due to a direct effect of the alkylating agent and its limited uptake by hepatocytes. Higher doses have been shown to cause liver injury in experimental animals.

Outcome and Management

The severity of the liver injury linked to streptozocin therapy has been generally mild, transient and without symptoms or jaundice. Streptozocin has not been linked to cases of chronic hepatitis or vanishing bile duct syndrome. There is no information on cross sensitivity to hepatic injury between streptozocin and other antineoplastic agents.

Drug Class: Antineoplastic Agents



Streptozocin – Zanosar®


Antineoplastic Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 23 August 2016

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