(strep toe ZOE sin)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Zanosar: 1 g (1 ea)
Brand Names: U.S.
- Antineoplastic Agent, Alkylating Agent
- Antineoplastic Agent, Alkylating Agent (Nitrosourea)
Inhibits DNA synthesis by alkylation and cross-linking the strands of DNA, and by possible protein modification; cell cycle nonspecific
Concentrates in liver, kidney, and pancreatic beta cells
Rapid; primarily hepatic
Urine (primarily; as parent drug and metabolites)
Onset of Action
1500 mg/m2 once weekly: Onset of response: 17 days; median time to maximum response: 35 days
Use: Labeled Indications
Treatment of metastatic islet cell carcinoma of the pancreas (symptomatic or progressive disease)
Off Label Uses
Adrenal carcinoma, metastatic
Data from a randomized, controlled, open-label, parallel-group study supports the use of streptozocin in the treatment of metastatic adrenal carcinoma. In this phase III study comparing mitotane in combination with etoposide, doxorubicin in combination with cisplatin (EDP regimen), and streptozocin in combination with mitotane, the response rate and progression free survival were significantly better with EDP arm, but there was no difference in overall survival between the groups [Fassnacht 2012]. Additional data from a phase II study also supports the use of streptozocin in the treatment of metastatic adrenal carcinoma. In this study, evaluating streptozocin in combination with mitotane, either complete or partial response occured in 36.4% of patients resulting in a 2 year survival of 70% and a 5 year survival rate of 32.5% [Khan 2000].
There are no contraindications listed within the manufacturer’s labeling.
Note: Streptozocin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017; Roila 2016).
Pancreatic islet cell carcinoma, metastatic: IV:
Daily schedule: 500 mg/m2/day for 5 consecutive days every 6 weeks until maximum benefit or until unacceptable toxicity
Weekly schedule: 1000 mg/m2 once weekly; if therapeutic response not achieved after 2 weeks, may escalate dose to a maximum of 1500 mg/m2 weekly
Off-label dosing: 1000 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)
Adrenal carcinoma, metastatic (off-label use): IV: 1000 mg once daily for 5 days (cycle 1) followed by 2000 mg on day 1 (subsequent cycles) every 3 weeks (in combination with mitotane) (Fassnacht, 2012; Khan 2000)
Refer to adult dosing. Select dose cautiously, beginning at the lower end of dosing range.
Dosing: Renal Impairment
No dosage adjustment provided in the manufacturer’s labeling; however, it is recommended to use clinical judgment weighing benefit vs risk of renal toxicity in patients with pre-existing renal impairment. The following dosing adjustments have been recommended (Aronoff, 2007): Adults (based on a usual dose of 500 mg/m2):
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 10-50 mL/minute: Administer 75% of dose
CrCl <10 mL/minute: Administer 50% of dose
Dosing: Hepatic Impairment
No dosage adjustment provided in the manufacturer’s labeling. However, streptozocin is rapidly hepatically metabolized; dose should be decreased in patients with severe liver disease.
Dosing: Adjustment for Toxicity
Bone marrow suppression or hepatic dysfunction: May require dosage reduction or discontinuation.
ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).
Reconstitute powder with 9.5 mL D5W or NS to a concentration of 100 mg/mL. May further dilute for infusion in D5W or NS.
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.
Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F). Protect from light. The manufacturer recommends use within 12 hours of reconstitution; vial does not contain a preservative.
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
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. 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. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. 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. Consider therapy modification
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
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% (Limited to important or life-threatening): Anemia, bone marrow depression (nadir: 2 to 3 weeks), confusion, depression, diabetes insipidus, hepatic insufficiency, lethargy, leukopenia, metastases, thrombocytopenia
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: Hematologic toxicity has been observed. Mild bone marrow suppression (rare) may occur; 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.
• 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.
• 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.
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
Pregnancy Risk Factor
Teratogenic events have been observed in animal reproduction studies.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea. Have patient report immediately to prescriber signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), severe nausea, vomiting, depression, confusion, severe loss of strength and energy, or severe injection site redness, pain, edema, or irritation (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: alkylating agents
Other brands: Zanosar