Generic Name: Streptozocin
Class: Antineoplastic Agents
VA Class: AN200
Chemical Name: 2-Deoxy-2-[[(methylnitrosoamino)carbonyl]amino]-d-glucose
Molecular Formula: C8H15N3O7
CAS Number: 18883-66-4
- Experience of Supervising Clinician
Administer only under supervision of qualified clinicians experienced in use of cytotoxic therapy.4 Hospitalization not required; however, adequate diagnostic and treatment facilities should be readily available to monitor drug tolerance and to manage complications.4
- Major Toxicities
Renal toxicity is dose related and cumulative; may be severe or fatal.4
Nausea and vomiting may be severe and/or treatment limiting.4
Hepatic dysfunction, diarrhea, and hematologic changes observed in some patients.4
Streptozocin is mutagenic.4 When given parenterally, found to be tumorigenic or carcinogenic in some rodents.4
Weigh benefits against known toxic effects; clinician must be familiar with prescribing information before beginning therapy.4
Antineoplastic agent; a nitrosourea-derivative alkylating antibiotic.1 2 3 4 5 6 7 8 14 15 16 17 a
Uses for Zanosar
Pancreatic Islet Cell Carcinoma
Treatment of metastatic islet cell carcinoma of the pancreas;4 136 used alone3 13 26 33 34 35 36 37 38 40 41 42 43 71 72 or in combination with other antineoplastic agents (e.g., doxorubicin, fluorouracil).36 37 39 136
Effective in patients with functional4 13 33 34 35 36 37 38 40 41 42 43 48 49 50 51 52 71 72 73 84 85 86 87 88 89 99 100 101 102 or nonfunctional4 33 37 39 and beta13 33 34 35 36 37 38 40 41 42 43 48 49 50 51 52 71 72 or non-beta37 73 84 85 86 87 88 89 99 100 101 102 103 104 105 islet cell tumors. Appears to be equally effective against functional or nonfunctional islet cell tumors.33 37
Currently the most active single agent for treatment of metastatic islet cell carcinoma of the pancreas.3 26 33 34 35 36 37 38 40 Combination therapy with fluorouracil associated with higher overall and complete response rates; however, effect on survival not established.36 37 81 85 100
Because tumor may be indolent,37 61 122 and because of streptozocin’s nephrotoxic4 33 and emetogenic122 potential, limit use to symptomatic or progressive metastatic disease.4 33 122
Carcinoid Tumor and Syndrome
Used alone36 43 59 106 or in combination with other antineoplastic agents3 63 94 136 (e.g., cyclophosphamide,94 fluorouracil,94 136 cyclophosphamide with fluorouracil and doxorubicin3 ).
When used alone, objective responses were partial and of short duration.36 43 59 106 Exact role in combination chemotherapy not established.3 94
Treatment of pancreatic adenocarcinoma†.3 36 40 43 59 62 69 70 74 75 76 77 78 110 111
Minimally effective as single agent.36 40 43 59 Role in combination chemotherapy regimens not yet determined.3 76 77 122
Zanosar Dosage and Administration
Consult specialized references for procedures for proper handling and disposal of antineoplastics.4
Use protective gloves during handling of streptozocin powder and preparation of solutions; topical contact may be carcinogenic hazard.4 (See Dermatologic Effects under Cautions.)
If skin or mucosal contact occurs, wash affected area(s) immediately and thoroughly with soap and water.4
Use antiemetic therapy to prevent acute and delayed emesis.137 (See GI Effects under Cautions.)
Measure response to therapy by monitoring for decrease or disappearance of signs or symptoms of disease.3 13 33 34 35 36 37 38 40 41 42 43 48 49 50 51 52 55 71 72 79 80 81 82 83 84 85 86 87 88 89 91 99 101 103 104 105 For functional or nonfunctional islet cell tumors, monitor for reductions in tumor size and/or organomegaly (e.g., pancreatic and/or extrapancreatic masses).4 33 34 35 36 37 38 40 41 42 43 48 49 50 51 52 63 71 72 79 80 81 82 83 84 85 86 87 88 89 99 100 101 102 103 104 105 For functional tumors, also may monitor appropriate polypeptide hormone concentrations (e.g., insulin, gastrin).4 33 34 35 36 37 38 40 41 42 43 48 49 50 51 52 63 71 72 79 80 81 82 83 84 85 86 87 88 89 99 100 101 102 103 104 105
Administer by direct IV injection3 4 32 35 37 40 43 70 73 74 77 79 83 or by IV infusion.3 4 13 35 38 40 42 60 81 Intra-arterial† infusion not recommended.3 4 33 35 71 73 79 80 89 118 (See Intra-arterial Infusion under Dosage and Administration.)
Contains no preservatives; vials not intended for multiple-dose withdrawal.4
For solution and drug compatibility information, see Compatibility under Stability.
Reconstitute vial containing 1 g of streptozocin with 9.5 mL of 5% dextrose or 0.9% sodium chloride injection to provide a solution containing 100 mg/mL.4
Rate of Administration
Administer by rapid IV injection.4 32 35 37 40 70 74 77
For solution and drug compatibility information, see Compatibility under Stability.
Reconstitute vial containing 1 g of streptozocin with 9.5 mL of 5% dextrose or 0.9% sodium chloride injection to provide a solution containing 100 mg/mL.4
For IV infusion, may further dilute in 5% dextrose or 0.9% sodium chloride injection4 or in 5% dextrose and 0.9% sodium chloride injection.121 132
Rate of Administration
Administer over a short or prolonged period.4
Usually administered as intermittent IV infusions over 15 minutes to 6 hours.13 35 38 40 42 43 73 78 81 83
Continuous 5-day IV infusions may be associated with increased CNS toxicity.60 (See CNS Effects under Cautions.)
Not recommended by manufacturer pending evaluation of possibility that adverse renal effects may be evoked more rapidly.b (See Renal Effects under Cautions.)
Administered via an appropriately placed catheter using a controlled-infusion device.35 71 73 79 80 118
Dilute in 5% dextrose or 0.9% sodium chloride injection.35 71 73 79 80 118
Rate of Administration
Infuse over 1–2 hours.35 71 73 79 80 118
Optimize results and minimize adverse effects by basing dosage on clinical, renal, hematologic, and hepatic responses and tolerance of the patient.3 4 33
Consult published protocols for dosages of streptozocin and other chemotherapeutic agents and for method and sequence of administration.a
Do not administer repeat course until renal, hematologic, and hepatic functions are within acceptable limits.4 33 (See Renal Effects, Hematologic Effects, and also Hepatic Effects under Cautions.)
Pancreatic Islet Cell Carcinoma
500 mg/m2 daily for 5 consecutive days; repeat every 6 weeks until optimal benefit or treatment-limiting toxicity occurs.4 Do not exceed 500 mg/m2 daily.4
May produce more severe nausea and vomiting than weekly regimen; however, may be more tolerable and acceptable because of the longer interval between periods of treatment-induced nausea and vomiting.37
Ideal duration of maintenance therapy unknown.4
Initially, 1 g/m2 once weekly for two weeks; then, may increase dose if therapeutic response is not achieved and no clinically important drug-related toxicity occurs.4 Do not exceed single dose of 1.5 g/m2; higher dosages may cause azotemia.4
Median time to onset of therapeutic response is approximately 17 days;4 33 median total cumulative dose to onset of response is 2 g/m2.4 33
Median time to maximum therapeutic response is approximately 35 days;4 33 median total cumulative dose to achieve maximum response is 4 g/m2.4 33
Ideal duration of maintenance therapy unknown.4
1–4 g/m2 once every 1–6 weeks for at least 1–4 courses of therapy.33 35 71 73 79 80 89 118 Safety not established.4 33 (See Intra-arterial Infusion under Dosage and Administration.)
Pancreatic Islet Cell Carcinoma
Maximum 500 mg/m2 daily.4
Maximum 1.5 g/m2 once weekly.4
Clcr 10–50 mL/minute: 75% of usual dosage.120
Clcr <10 mL/minute: 50% of usual dosage.120
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.4 Start at lower end of dosage range.4 (See Geriatric Use under Cautions.)
Cautions for Zanosar
Highly toxic, with low therapeutic index; therapeutic response not likely to occur without some evidence of toxicity.3 4 8 13 33 (See Boxed Warning.)
Renal toxicity occurs in 25–75% of patients.3 13 33 43 59 Dose limiting and cumulative; may be severe or fatal.3 4 13 33 43 53 54 55 56 57 58 59
Renal toxicity may manifest as azotemia, anuria, proteinuria, hypophosphatemia, hyperchloremia, and proximal renal tubular acidosis (possibly associated with Fanconi-like syndrome [e.g., glycosuria, acetonuria, aminoaciduria]).3 4 8 13 32 33 40 43 53 54 55 56 57 58 59 Hypokalemia and hypocalcemia also have occurred.3
Hypophosphatemia8 13 53 56 or mild proteinuria4 13 33 40 59 may be earliest sign of nephrotoxicity and may indicate impending further deterioration of renal function.3 4 40 53 Increased BUN and Scr may occur later if streptozocin is continued.13
Mild adverse renal effects (e.g., mild proteinuria) may be reversible if streptozocin is discontinued; 3 13 however, nephrotoxicity may be irreversible or fatal if drug is continued despite nephrotoxic manifestations.3 13 33 39 56 57 58
Intra-arterial† administration may increase risk and/or precipitate more rapid development of nephrotoxicity.33 b (See Intra-arterial Infusion under Dosage and Administration.)
Nephrogenic diabetes insipidus reported rarely.4 135
Long-term effects on renal function not fully known.58 Cumulative, delayed nephrotoxicity and chronic renal failure reported rarely following discontinuance of streptozocin.58
Manufacturer recommends obtaining serial urinalyses, Clcr, BUN, Scr, and electrolyte concentrations prior to and at least weekly during streptozocin therapy and then weekly for 4 weeks after discontinuance of drug.4 Alternatively, some clinicians suggest that assessment of renal function prior to each course of therapy is sufficient in most patients.122 Serial urinalysis is particularly important for early detection of proteinuria; if proteinuria is detected, quantify with a 24-hour urine collection.4
Adequate hydration may help reduce risk of nephrotoxicity to renal tubular epithelium by decreasing renal and urinary concentrations of streptozocin and/or metabolites;4 8 13 however, role of hydration not clearly established.13 122
Reduce dosage or discontinue streptozocin if substantial renal toxicity occurs.4
Use in patients with impaired renal function only when benefits outweigh known risk of nephrotoxicity.4 (See Renal Impairment under Cautions.)
Do not use in combination or concomitantly with other potential nephrotoxins.4 (See Nephrotoxic Drugs under Interactions.)
Possible carcinogenic hazard from topical exposure if improperly handled.4 132
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.4 Use during pregnancy only when potential benefits justify possible risks to fetus.4
Severe nausea and vomiting occur in most patients (>90%),137 usually beginning 1–4 hours following administration; may persist for ≥24 hours.3 13 33 May require discontinuance of streptozocin.3 4 13 33 37 137
Incidence and/or severity of nausea and vomiting may be reduced with 5-day continuous IV infusions compared with rapid, intermittent IV administration.60
Aggressive antiemetic therapy during early courses of emetogenic chemotherapy is the best way to prevent anticipatory nausea and vomiting.137 Behavioral therapy may be useful; benzodiazepines also may be useful, although evidence is lacking.137
To prevent acute emesis associated with highly emetogenic chemotherapy (e.g., streptozocin), ASCO recommends premedication with a 3-drug antiemetic regimen (a selective 5-HT3 receptor antagonist, dexamethasone, and aprepitant);137 currently available selective 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron) are comparably effective.137
To prevent delayed emesis, ASCO recommends administration of a 2-drug regimen (dexamethasone and aprepitant) following administration of highly emetogenic chemotherapy.137
Diarrhea has occurred occasionally.3 4 33 Duodenal ulcer reported rarely; however, not directly associated with streptozocin.40
Mild to moderate myelosuppression (e.g., leukopenia, thrombocytopenia, anemia [decreased hematocrit and hemoglobin]) reported; 3 4 13 33 severe myelosuppression (e.g., substantial leukopenia and thrombocytopenia) leading to sepsis and death reported rarely.4 13 33 Cumulative and usually reversible;3 4 13 33 may be more severe in patients previously treated with other antineoplastic agents or radiation therapy.3 13 67 68 Leukocyte and platelet nadirs usually occur at 1–2 weeks after administration.13
Asymptomatic eosinophilia also reported; disappears following discontinuance of streptozocin.13 43 60
Monitor CBC at least weekly.4 Adjust dosage or discontinue streptozocin as needed.4
Minimal, transient increases in serum AST, ALT, LDH, and/or alkaline phosphatase concentrations reported.4 13 32 33 37 Increased serum bilirubin concentration33 and hypoalbuminemia also reported.4 Severe and fatal hepatic effects reported rarely.61
Manufacturer recommends performing liver function tests at least weekly;4 alternatively, some clinicians recommend monitoring liver function just prior to initiating each course of therapy.133 Adjust dosage or discontinue streptozocin as needed.4
Mild to moderate, reversible abnormalities of glucose tolerance reported in some patients.3 4 32 33 43 Insulin shock with severe hypoglycemia, requiring treatment with IV dextrose, has occurred rarely in patients with insulinomas,4 8 33 61 usually within 24 hours after administration.33
Glycosuria without hyperglycemia reported in some patients.32 33 40 43
Manifestations of local inflammation (e.g., edema, erythema, burning, tenderness), usually resolving the same day or within a few days, reported following extravasation of streptozocin.4 Severe tissue lesions and necrosis also reported following extravasation.4 62
Burning sensation, extending from site of injection up the arm, reported in some patients, especially following rapid IV injection.3 33 40
Confusion, lethargy, and depression reported with continuous IV infusion for 5 days;4 60 not associated with other methods of administration.3
Adequate Patient Evaluation and Monitoring
Monitor closely, particularly for evidence of adverse renal, hematologic, and hepatic effects.4 (See Renal Effects, Hematologic Effects, and also Hepatic Effects under Cautions.)
Do not administer repeat course until renal, hematologic, and hepatic functions are within acceptable limits.4 33
Category D.4 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Not known whether streptozocin is distributed into milk.4 Discontinue nursing because of potential risk to nursing infants.b
Safety and efficacy not established.63 132
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; clinical experience has not revealed age-related differences.4 Select dosage with caution, usually starting at low end of dosage range. 4 (See Geriatric Patients under Dosage and Administration.)
Weigh benefit against risk of serious renal damage.4 (See Renal Effects under Cautions.) Dosage adjustments necessary based on degree of renal impairment.120 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
Severe nausea and vomiting,3 4 13 33 37 137 nephrotoxicity,3 4 13 53 54 55 56 57 58 myelosuppression.3 4 13 33
Interactions for Zanosar
Drugs that Decrease Hematopoiesis
Possible increased risk of hematologic toxicity.132
Possible cumulative nephrotoxicity; avoid combination or concomitant use.4
Possible additive adverse effects (e.g., myelosuppression)4
Antineoplastics, nitrosoureas (e.g., carmustine)
Possible synergistic adverse hematologic effects; mechanism unknown3 68
Possible increased half-life of doxorubicin, resulting in severe myelosuppression4 61 67
Decrease doxorubicin dosage if used concurrently4 61 67
Possible decreased cytotoxic effects of streptozocin on beta cells3 4 66
Avoid concomitant administration66
Poorly absorbed following oral administration.7 126 Not active orally; must be administered IV.4
Following IV or intraperitoneal administration in animals, rapidly distributed into liver, kidneys, intestine, and pancreas; lower concentrations in skeletal muscle, spleen, lungs, heart, and thymus.44 124 125
Does not appear to cross the blood-brain barrier; however, metabolites readily distribute into CSF.45
Readily crosses the placenta in monkeys.4 Not known whether streptozocin crosses the placenta or is distributed into milk in humans.4
Extensively metabolized, probably in the liver and kidneys.3 4 44 45 46 47
Excreted principally in urine as unchanged drug (10%) and metabolites (60–70%).3 5 8 44 45 46 47 May be excreted in expired air (5%) or in feces (<1%).45 46
Biphasic;8 45 46 terminal half-life is approximately 35–40 minutes for streptozocin or >40 hours for metabolites.45 46
Powder for Injection
2–8°C; protect from light.4 Store in carton.4
Reconstituted or diluted solution (i.e., diluted with 5% dextrose and 0.9% sodium chloride injection to final concentration of 2 mg/mL) stable for 48 hours at room temperature or for ≥96 hours at 2–8°C.121 123 However, because product contains no preservatives, manufacturer recommends discarding reconstituted or diluted solution within 12 hours after preparation.4
For information on systemic interactions resulting from concomitant use, see Interactions.
Piperacillin sodium–tazobactam sodium
Active against gram-positive and gram-negative bacteria;1 2 7 8 cytotoxicity precludes use as an anti-infective agent.3 15 16 17 18 19 20
Precise mechanism unknown.4 5 Alkylates DNA, causing interstrand cross-linking.3 9 23 24 25 Weak alkylator compared with other nitrosoureas.3 12
Inhibits DNA synthesis in bacterial and mammalian cells.3 4 9 10 12 15 21 22 Blocks progression of cells into mitosis;15 however, cycle-phase nonspecific.4 8 15 Does not inhibit RNA or protein synthesis.15 17 22
Marked specificity for pancreatic beta and exocrine cells.8 18 26 28
Advice to Patients
Risk of adverse renal, GI, hematologic, and hepatic effects.4 Importance of adherence to medical and laboratory appointment schedules.4
Possible confusion, lethargy, and depression if receiving continuous IV infusion for 5 days.4 Potential risk in driving or using complex machinery.4
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., renal disease).4
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.4
Importance of informing patients of other precautionary information.4 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Zanosar (with anhydrous citric acid 220 mg)
AHFS DI Essentials. © Copyright 2018, Selected Revisions October 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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