Streptozocin (Zanosar) — Clinical FAQs

Question 1

What is Streptozocin FDA-approved to treat?

Accepted Answer

Streptozocin is FDA-approved for the following oncology indications: 1. Metastatic islet cell carcinoma of the pancreas (pancreatic neuroendocrine tumors — pNETs): symptomatic or progressive disease; used as monotherapy or in combination with 5-fluorouracil or doxorubicin.

Question 2

How does Streptozocin work (mechanism of action)?

Accepted Answer

Streptozocin is a nitrosourea-type alkylating agent naturally produced by Streptomyces achromogenes. It exerts its cytotoxic effect by transferring a methylnitrosourea moiety to DNA, resulting in alkylation predominantly at the O6-position of guanine, as well as N7-guanine and O3-adenine adducts, causing DNA strand breaks and inhibition of DNA synthesis. Unlike classical nitrosoureas (carmustine, lomustine), streptozocin does not produce significant carbamoylation of proteins. Streptozocin is selectively toxic to pancreatic beta-islet cells through a mechanism involving uptake via the GLUT2 glucose transporter, which is highly expressed in islet cells, leading to specific destruction of insulin-secreting cells. This selective uptake also forms the basis of its therapeutic activity in pancreatic neuroendocrine tumors (islet cell carcinomas), where GLUT2 expression facilitates preferential drug accumulation within the tumor.

Question 3

How is Streptozocin administered?

Accepted Answer

Streptozocin is administered Intravenous (IV). Daily schedule: 500 mg/m² IV daily for 5 consecutive days every 6 weeks until maximum benefit or toxicity occurs.

Question 4

What are the most common side effects of Streptozocin?

Accepted Answer

The most commonly reported side effects of Streptozocin (≥10% incidence) include: Severe nausea and vomiting (≥90%; highly emetogenic — considered one of the most emetogenic non-cisplatin agents), Renal tubular dysfunction / proteinuria / glucosuria (≥60%; may precede azotemia), Elevated BUN and serum creatinine (≥65% with cumulative dosing), Hypophosphatemia (from tubular wasting), Diarrhea (≥10%) and others (9 total). Consult your oncologist for complete prescribing information.

Question 5

Does Streptozocin have a black box warning?

Accepted Answer

Yes. Streptozocin carries FDA black box warning(s) regarding: 1. Renal Toxicity (Dose-Limiting): Streptozocin causes cumulative, dose-limiting nephrotoxicity, which is the primary toxicity and most common cause of treatment discontinuation. Manifestations include azotemia, tubular acidosis (Fanconi syndrome — glucosuria, phosphaturia, aminoaciduria, tubular acidosis), and irreversible renal failure. Monitor renal function (BUN, serum creatinine, urinalysis for glucosuria and proteinuria, and creatinine clearance) before each course of therapy. Reduce dose or discontinue therapy based on the degree of renal impairment. Do not administer concomitantly with other nephrotoxic drugs if avoidable. 2. Hepatotoxicity: Streptozocin causes hepatic toxicity manifested by elevated LFTs; monitor liver function tests at baseline and before each cycle. 3. Myelosuppression: Streptozocin causes myelosuppression; obtain CBC before each course and withhold for significant cytopenias.

Question 6

Is Streptozocin safe during pregnancy?

Accepted Answer

Streptozocin pregnancy safety: Category D — streptozocin is teratogenic and embryotoxic in animal models and should be considered potentially teratogenic in humans. Advise patients of reproductive potential to use effective contraception during and after treatment. Streptozocin should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Streptozocin — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms