Version May 2024
Streptozocin should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. A patient need not be hospitalized but should have access to a facility with a laboratory and supportive resources sufficient to monitor drug tolerance and to protect and maintain a patient compromised by drug toxicity. The physician must judge the possible benefit to the patient against the known toxic effects of this drug in considering the advisability of therapy with streptozocin. The physician should be familiar with the following text before making a judgment and beginning treatment.
Renal toxicity is dose-related and cumulative and may be severe or fatal. Other major toxicities are nausea and vomiting, which may be severe and at times treatment-limiting. In addition, liver dysfunction, diarrhea and hematological changes have been observed in some patients.
Streptozocin is mutagenic. When administered parenterally, it has been found to be tumorigenic or carcinogenic in some rodents.
Note: Streptozocin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017; Roila 2016).
Adrenocortical carcinoma, metastatic (off-label use): IV: 1,000 mg once daily for 5 days (cycle 1) followed by 2,000 mg on day 1 (subsequent cycles) every 3 weeks until disease progression or unacceptable toxicity (in combination with mitotane) (Fassnacht 2012; Khan 2000).
Gastrointestinal neuroendocrine tumors (off-label use): IV: 500 mg/m2 on days 1 to 5 every 10 weeks (in combination with fluorouracil) until disease progression or unacceptable toxicity (Sun 2005) or 1,000 mg/m2 once every 3 weeks for 3 cycles, if no progression may continue for up to a total of 6 cycles in the absence of unacceptable toxicity (in combination with leucovorin, fluorouracil and cisplatin) (Turner 2010).
Pancreatic neuroendocrine tumors (metastatic): IV:
Daily schedule: 500 mg/m2 once daily for 5 consecutive days every 6 weeks (in combination with either doxorubicin or fluorouracil) until disease progression or unacceptable toxicity (Moertel 1992)
Weekly schedule: 1,000 mg/m2 once weekly; if therapeutic response not achieved after 2 weeks, may escalate dose to a maximum of 1,500 mg/m2 weekly
Alternate schedules (off-label dosing): 1,000 mg/m2 once every 3 weeks for up to 6 cycles (in combination with leucovorin, fluorouracil and cisplatin) (Turner 2010) or 400 mg/m2 days 1 to 5 every 4 weeks (in combination with fluorouracil and doxorubicin) until disease progression or unacceptable toxicity (Kouvaraki 2004) or 500 mg/m2 on days 1 to 5 every 5 or 6 weeks (in combination with fluorouracil) for up to 1 year if best response is stable disease (Dilz 2015)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; however, it is recommended to use clinical judgment weighing benefit versus risk of renal toxicity in patients with preexisting renal impairment. The following dosing adjustments have been recommended (Aronoff 2007) (based on a usual dose of 500 mg/m2):
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 10 to 50 mL/minute: Administer 75% of dose
CrCl <10 mL/minute: Administer 50% of dose
Hepatic impairment prior to treatment: There are no dosage adjustments provided in the manufacturer’s labeling. However, streptozocin is rapidly hepatically metabolized; use with caution.
Hepatotoxicity during treatment: May require dosage reduction or discontinuation.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).
Bone marrow suppression: May require dosage reduction or discontinuation.
Refer to adult dosing. Select dose cautiously, beginning at the lower end of dosing range.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
Endocrine & metabolic: Decreased glucose tolerance, glycosuria, hyperglycemia, hypoalbuminemia, hypoglycemia, hypophosphatemia, increased lactate dehydrogenase
Gastrointestinal: Diarrhea, nausea, vomiting
Genitourinary: Anuria, azotemia, nephrotoxicity, proteinuria
Hepatic: Increased serum transaminases
Local: Injection site reaction (includes burning sensation at injection site, erythema at injection site, inflammation at injection site, irritation at injection site, swelling at injection site, tenderness at injection site)
Renal: Increased blood urea nitrogen, increased serum creatinine, renal insufficiency, renal tubular acidosis
<1%, postmarketing, and/or case reports: Anemia, bone marrow depression (nadir: 2 to 3 weeks), confusion, depression, diabetes insipidus, hepatic insufficiency, lethargy, leukopenia, metastases, thrombocytopenia
There are no contraindications listed within the manufacturer's labeling.
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: Hematologic toxicity has been observed. Mild bone marrow suppression (rare) may occur (usually mild anemia); monitor blood counts weekly. May require dosage reduction or discontinuation.
• CNS effects: May cause confusion, lethargy or depression; caution patients about performing tasks that require mental alertness (eg, operating machinery or driving).
• Extravasation/tissue irritation: Streptozocin is an irritant with vesicant-like properties. Avoid extravasation. Local tissue irritation or inflammation (burning, edema, erythema, tenderness) may occur, but usually resolves within a few days.
• Gastrointestinal events: [US Boxed Warning]: Diarrhea has been observed. May cause severe nausea and vomiting. Streptozocin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016).
• Glucose intolerance: Mild-to-moderate glucose intolerance may occur; generally is reversible. Insulin shock with hypoglycemia has been observed.
• Hepatotoxicity: [US Boxed Warning]: Liver dysfunction has been observed. Hepatotoxicity may be characterized by elevated transaminases and LDH, or by hypoalbuminemia; monitor liver function weekly. Hepatic dysfunction may require dosage reduction or discontinuation.
• Renal toxicity: [US Boxed Warning]: Renal toxicity is dose-related and cumulative; may be severe or fatal. Azotemia, anuria, hypophosphatemia, glycosuria and renal tubular acidosis have been reported. Adequate hydration may reduce the risk for nephrotoxicity. Monitor renal function (BUN, serum creatinine, and serial urinalysis) and electrolytes prior to, weekly during, and after each treatment course. Mild proteinuria is an early sign of renal toxicity; if proteinuria is detected with urinalysis, obtain 24-hour urine collection. Avoid use in combination with other nephrotoxic medications. Use with caution in patients with pre-existing renal disease.
• Secondary malignancy: [US Boxed Warning]: Streptozocin is mutagenic; parenteral use is tumorigenic and carcinogenic in animals.
Other warnings/precautions:
• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Administer in a facility with sufficient access to lab and supportive resources for monitoring toxicities.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Zanosar: 1 g (1 ea)
No
Solution (reconstituted) (Zanosar Intravenous)
1 g (per each): $419.08
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IV: Streptozocin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016).
Administer as either a rapid IV injection or as short or prolonged infusion.
Irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) for preparation. Double gloving, a gown, and (if dosage form allows) CSTDs are required during administration (NIOSH 2016).
Pancreatic neuroendocrine tumors: Treatment of metastatic islet cell carcinoma of the pancreas (symptomatic or progressive disease)
Adrenocortical carcinoma, metastatic; Gastrointestinal neuroendocrine tumors
Streptozocin may be confused with streptomycin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Adverse events have been observed in animal reproduction studies.
It is not known if streptozocin is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended.
Renal function tests, including BUN, serum creatinine, and serial urinalysis, and serum electrolytes (at baseline, weekly during, and for 4 weeks after treatment); 24-hour urine collection if proteinuria is detected on urinalysis; liver function tests (weekly), CBC with differential and platelets (weekly), blood glucose; monitor infusion site
Streptozocin inhibits DNA synthesis by alkylation and cross-linking the strands of DNA, and by possible protein modification; cell cycle nonspecific
Onset: 1,500 mg/m2 once weekly: Onset of response: 17 days; median time to maximum response: 35 days
Distribution: Concentrates in liver, kidney, and pancreatic beta cells
Metabolism: Rapid; primarily hepatic
Half-life elimination: <1 hour (Perry 2012)
Excretion: Urine (primarily; as parent drug and metabolites)
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