Advanced Breast Cancer: Learn about treatment options.

Zanosar

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

Warning(s)

  • 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

Introduction

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

Slideshow: Prescription Drug Addiction - Are You at Risk?

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

Palliative treatment of metastatic carcinoid tumor or syndrome.3 13 36 39 43 59 63 92 93 94 106 136

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

Pancreatic Adenocarcinoma

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

General

Administration

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

IV Injection

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution

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

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution

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

Dilution

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.)

Intra-arterial Infusion

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

Dilution

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

Dosage

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.)

Adults

Pancreatic Islet Cell Carcinoma
Consecutive-Day Regimen
IV

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

Weekly Regimen
IV

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

Intra-arterial Regimen
Intra-arterial

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.)

Prescribing Limits

Adults

Pancreatic Islet Cell Carcinoma
Consecutive-Day Regimen
IV

Maximum 500 mg/m2 daily.4

Weekly Regimen
IV

Maximum 1.5 g/m2 once weekly.4

Special Populations

Renal Impairment

Clcr 10–50 mL/minute: 75% of usual dosage.120

Clcr <10 mL/minute: 50% of usual dosage.120

Geriatric Patients

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

Warnings/Precautions

Warnings

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 Effects

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.)

Dermatologic Effects

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

Major Toxicities

GI Effects

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

Hematologic Effects

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

Hepatic Effects

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

Metabolic Effects

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

Local Effects

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

CNS Effects

Confusion, lethargy, and depression reported with continuous IV infusion for 5 days;4 60 not associated with other methods of administration.3

General Precautions

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

Specific Populations

Pregnancy

Category D.4 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether streptozocin is distributed into milk.4 Discontinue nursing because of potential risk to nursing infants.b

Pediatric Use

Safety and efficacy not established.63 132

Geriatric Use

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.)

Renal Impairment

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

Nephrotoxic Drugs

Possible cumulative nephrotoxicity; avoid combination or concomitant use.4

Specific Drugs

Drug

Interaction

Comments

Antineoplastics

Possible additive adverse effects (e.g., myelosuppression)4

Antineoplastics, nitrosoureas (e.g., carmustine)

Possible synergistic adverse hematologic effects; mechanism unknown3 68

Doxorubicin

Possible increased half-life of doxorubicin, resulting in severe myelosuppression4 61 67

Decrease doxorubicin dosage if used concurrently4 61 67

Phenytoin

Possible decreased cytotoxic effects of streptozocin on beta cells3 4 66

Avoid concomitant administration66

Zanosar Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed following oral administration.7 126 Not active orally; must be administered IV.4

Distribution

Extent

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

Elimination

Metabolism

Extensively metabolized, probably in the liver and kidneys.3 4 44 45 46 47

Elimination Route

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

Half-life

Biphasic;8 45 46 terminal half-life is approximately 35–40 minutes for streptozocin or >40 hours for metabolites.45 46

Stability

Storage

Parenteral

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

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Drug Compatibility

Y-Site CompatibilityHID

Compatible

Amifostine

Etoposide phosphate

Filgrastim

Gemcitabine HCl

Granisetron HCl

Melphalan HCl

Ondansetron HCl

Teniposide

Thiotepa

Vinorelbine tartrate

Incompatible

Allopurinol sodium

Aztreonam

Cefepime HCl

Piperacillin sodium–tazobactam sodium

Actions

  • 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.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Streptozocin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

1 g

Zanosar (with anhydrous citric acid 220 mg)

Sicor

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Varva JJ, DeBoer C, Dietz A et al. Streptozotocin, a new antibacterial antibiotic. Antibiot Annu. 1959-60:230-5.

2. Lewis C, Barbiers AR. Streptozotocin, a new antibiotic. In vitro and in vivo evaluation. Antibiot Annu. 1959-60:247-54.

3. Weiss RB. Streptozocin: a review of its pharmacology, efficacy, and toxicity. Cancer Treat Rep. 1982; 66:427-38. [IDIS 148368] [PubMed 6277485]

4. Pharmacia & Upjohn Company. Zanosar (streptozocin sterile powder) prescribing information. Kalamazoo, MI; 2003 Feb.

5. Trissel LA, Kleinman LM, Davignon JP et al. Investigational drug information. Drug Intell Clin Pharm. 1978; 12:404-6.

6. Herr RR, Jahnke HK, Argoudelis AD. The structure of streptozotocin. J Am Chem Soc. 1967; 89:4808-9. [PubMed 6074800]

7. White FR. Streptozotocin. Cancer Chemother Rep. 1963; 30:49-53. [PubMed 14051504]

8. Dorr RT, Fritz WL. Cancer chemotherapy handbook. New York: Elsevier/North Holland Inc.; 1980:632-40.

9. Lown JW, McLaughlin LW, Chang YM. Mechanism of action of 2-haloethyl nitrosoureas on DNA and its relation to their antileukemic properties. Bioorg Chem. 1978; 7:97-110.

10. Wheeler GP, Chumley S. Alkylating activity of 1,3-bis(2-chloroethyl)-1-nitrosoureas and related compounds. J Med Chem. 1966; 10:259-61.

11. Garrett ER. Prediction of stability in pharmaceutical preparations VII: the solution degradation of the antibiotic streptozotocin. J Am Pharm Assoc Sci Ed. 1960; 49:767-77.

12. Panasci LC, Fox PA, Schein PS. Structure-activity studies of methylnitrosourea antitumor agents with reduced murine bone marrow toxicity. Cancer Res. 1977; 37:3321-8. [PubMed 141978]

13. Schein PS, O’Connell MJ, Blom J et al. Clinical antitumor activity and toxicity of streptozotocin (NSC-85998). Cancer. 1974; 34:993-1000. [IDIS 51012] [PubMed 4371075]

14. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982:226.

15. Bhuyan BK. The action of streptozotocin on mammalian cells. Cancer Res. 1970; 30:2017-23. [PubMed 5456086]

16. Evans JS, Gerritsen GC, Mann KM et al. Antitumor and hyperglycemic activity of streptozotocin (NSC-37917) and its cofactor, U-15, 774. Cancer Chemother Rep. 1965; 48:1-6. [PubMed 4953644]

17. Bhuyan BK, Fraser TJ, Buskirk HH et al. Antileukemic activity of streptozotocin (NSC-85998) and its analogs. Cancer Chemother Rep. 1972; 56:709-20. [PubMed 4267348]

18. Rakieten N, Rakieten ML, Nadkarni MV. Studies on the diabetogenic action of streptozotocin (NSC-37917). Cancer Chemother Rep. 1963; 29:91-8. [PubMed 13990586]

19. Carter SK, Broder L, Friedman M. Streptozotocin and metastatic insulinoma. Ann Intern Med. 1971; 74:445-6. [PubMed 4324025]

20. Arison RN, Ciaccio EI, Glitzer MS et al. Light and electron microscopy of lesions in rats rendered diabetic with streptozotocin. Diabetes. 1967; 16:51-6. [PubMed 6015682]

21. Rosenkrantz HS, Carr HS. Differences in the action of nitrosomethylurea and streptozotocin. Cancer Res. 1970; 30:112-7. [PubMed 4909629]

22. Heinemann B, Howard AJ. Effect of compounds with both antitumor and bacteriophage-inducing activities on E. coli nucleic synthesis. Antimicrob Agents Chemother. 1965; 5:488-92. [PubMed 5327520]

23. Chatterji DC, Greene RF, Gallelli JF. Mechanism of hydrolysis of the halogenated nitrosoureas. J Pharm Sci. 1978; 67:1527-32. [IDIS 88325] [PubMed 30837]

24. Heidelberger C. Chemical carcinogenesis. Annu Rev Biochem. 1975; 44:79-121. [PubMed 1094923]

25. Montgomery JA, James R, McCaleb G et al. The modes of decomposition of 1,3-bis(2-chloroethyl)-1-nitrosourea and related compounds. J Med Chem. 1967; 10:668-74. [PubMed 6037060]

26. Hood JC, Zimmerman PF, Chatterji D. Comparison of streptozotocin and chlorozotocin administration factors. Contemp Pharm Pract. 1981; 4:107-11.

27. Heal JM, Fox PA, Schein PS. Effect of carbamoylation on the repair of nitrosourea-induced DNA alkylation damage in L1210 cells. Cancer Res. 1979; 39:82-9. [PubMed 153789]

28. Junod A, Lambert AE, Orci L et al. Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med. 1967; 126:201-5. [PubMed 4864021]

29. Dulin WE, Wyse BM. Studies on the ability of compounds to block the diabetogenic activity of streptozotocin. Diabetes. 1967; 18:459-66.

30. Schein PS, Cooney DA, Vernon ML. The use of nicotinamide to modify the toxicity of streptozotocin diabetes without loss of antitumor activity. Cancer Res. 1967; 27:2324-32. [PubMed 4295475]

31. Anderson T, Schein PS, McMenamin MG et al. Streptozotocin diabetes: correlation with extent of depression on pancreatic islet nicotinamide adenine dinucleotide. J Clin Invest. 1974; 54:672-7. [PubMed 4369217]

32. Sadoff L. Patterns of intravenous glucose tolerance and insulin response before and after treatment with streptozocin (NSC-85998) in patients with cancer. Cancer Chemother Rep. 1972; 56:61-9. [IDIS 24617] [PubMed 4260577]

33. Broder LE, Carter SK. Pancreatic islet cell carcinoma. II. Results of therapy with streptozotocin in 52 patients. Ann Intern Med. 1973; 79:108-18. [IDIS 36839] [PubMed 4352784]

34. Gefel A, Flatau E, Ayalon D et al. Malignant metastatic insulinoma treated with streptozotocin: report of a case and review of literature. Clin Endocrinol. 1975; 4:461-8.

35. Herbai G, Lundin A. Treatment of malignant metastatic pancreatic insulinoma with streptozotocin: review of 21 cases described in detail in the literature and report of complete remission of a new case. Acta Med Scand. 1976; 200:447-52. [IDIS 82137] [PubMed 189576]

36. Moertel CG. Clinical management of advanced gastrointestinal cancer. Cancer. 1975; 36:675-82. [PubMed 168961]

37. Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1980; 303:1189-94. [IDIS 124681] [PubMed 6252466]

38. Schein P, Kahn R, Gorden P et al. Streptozotocin for malignant insulinomas and carcinoid tumor: report of 8 cases and review of the literature. Arch Intern Med. 1973; 132:555-61. [IDIS 36535] [PubMed 4355081]

39. Chernicoff D, Bukowski RM, Groppe CW et al. Combination chemotherapy for islet cell carcinoma and metastatic carcinoid tumors with 5-fluorouracil and streptozotocin. Cancer Treat Rep. 1979; 63:795-6. [IDIS 101263] [PubMed 222449]

40. DuPriest RW, Huntington MC, Massey WH et al. Streptozotocin therapy in 22 cancer patients. Cancer. 1975; 35:358-67. [IDIS 51207] [PubMed 122912]

41. Taylor SG III, Schwartz TB, Zannini JJ et al. Streptozotocin therapy for metastatic insulinoma. Arch Intern Med. 1970; 126:654-7. [IDIS 14232] [PubMed 4319181]

42. Murray-Lyon IM, Eddleston AL, Williams R et al. Treatment of multiple hormone-producing malignant islet-cell tumour with streptozotocin. Lancet. 1968; 2:895-8. [PubMed 4176152]

43. Stolinsky DC, Sadoff L, Braunwald J et al. Streptozotocin in the treatment of cancer: phase II study. Cancer. 1972; 30:61-7. [IDIS 27238] [PubMed 4261143]

44. Bhuyan BK, Kuentzel SL, Gray LG et al. Tissue distribution of streptozotocin (NSC-85998). Cancer Chemother Rep. 1974; 58:157-65. [PubMed 4275384]

45. Adolphe AB, Glasofer ED, Troetel WM et al. Fate of streptozotocin (NSC-85998) in patients with advanced cancer. Cancer Chemother Rep. 1975; 59:547-56. [IDIS 56248] [PubMed 128410]

46. Adolphe AB, Glasofer ED, Troetel WM et al. Preliminary pharmacokinetics of streptozotocin, an antineoplastic antibiotic. J Clin Pharmacol. 1977; 17:379-88. [IDIS 82006] [PubMed 142097]

47. Karunanayake EH, Hearse DJ, Mellows G. The metabolic fate and elimination of streptozotocin. Biochem Soc Trans. 1975; 3:410-4. [PubMed 124280]

48. Blackard WG, Garcia AR, Brown CL. Effect of streptozotocin on qualitative aspects of plasma insulin in a patient with a malignant islet cell tumor. J Clin Endocrinol. 1970; 31:215-9.

49. Broder LE, Carter SK. Pancreatic islet cell carcinoma. I. Clinical features of 52 patients. Ann Intern Med. 1973; 79:101-7. [PubMed 4352783]

50. Murray-Lyon IM, Cassar J, Coulson R et al. Further studies on streptozotocin therapy for a multiple hormone-producing islet cell carcinoma. Gut. 1971; 12:717-20. [PubMed 4329097]

51. Schriebman PH, DeKoliren LG, Arky RA. Metastatic insulinoma treated with streptozotocin. Ann Intern Med. 1971; 74:399-403. [IDIS 19071] [PubMed 4324022]

52. Smith CK, Stoll RW, Vance J et al. Treatment of malignant insulinoma with streptozotocin. Diabetologia. 1971; 7:118-24. [PubMed 4325749]

53. Sadoff L. Nephrotoxicity of streptozotocin (NSC-85998). Cancer Chemother Rep. 1970; 54:457-9. [IDIS 16405] [PubMed 4334090]

54. Loftus L, Cuppage FE, Hoogstraten B. Clinical and pathological effects of streptozotocin. J Lab Clin Med. 1974; 84:407-13 (IDIS 45896) [IDIS 45896] [PubMed 4368506]

55. Myerowitz RL, Sartiano GP, Cavallo T. Nephrotoxic and cytoproliferative effects of streptozotocin: report of a patient with multiple hormone-secreting islet cell carcinoma. Cancer. 1976; 38:1550-5. [IDIS 78177] [PubMed 186169]

56. Fennell JS, Falls WF Jr. Streptozotocin nephrotoxicity: studies on the defect in renal tubular acidification. Clin Nephrol. 1981; 15:97-101. [PubMed 6260405]

57. Hall-Craggs M, Brenner DE, Vigorito RD et al. Acute renal failure and renal tubular squamous metaplasia following treatment with streptozotocin. Hum Pathol. 1982; 13:597-601. [PubMed 6281169]

58. Perry DJ, Weiss RB. Nephrotoxicity of streptozocin. Ann Intern Med. 1982; 96:122. [IDIS 142631] [PubMed 6459048]

59. Moertel CG, Reitemeier RJ, Schutt AJ et al. Phase II study of streptozotocin (NSC-85998) in the treatment of advanced gastrointestinal cancer. Cancer Chemother Rep. 1971; 55:303-7. [IDIS 20687] [PubMed 5115851]

60. Seibert K, Golub G, Smiledge P et al. Continuous streptozotocin infusion: a phase I study. Cancer Treat Rep. 1979; 63:2035-7. [IDIS 110544] [PubMed 160836]

61. Anon. Streptozocin (Zanosar). Med Lett Drugs Ther. 1982; 24:100-1. [PubMed 6290862]

62. Horton J, Gelber RD, Engstrom P et al. Trials of single-agent and combination chemotherapy for advanced cancer of the pancreas. Cancer Treat Rep. 1981; 65:65-8. [IDIS 134315] [PubMed 6452948]

63. Upjohn Company. Corporate product statement: Zanosar sterile powder. Kalamazoo, MI; [undated].

64. Rakieten N, Gordon BS, Cooney DA et al. Renal tumorigenic action of streptozotocin (NSC-85998) in rats. Cancer Chemother Rep. 1968; 52:563-7. [IDIS 7400] [PubMed 5743703]

65. Green MR, Anderson RE. Acute myelocytic leukemia following prolonged streptozocin therapy. Cancer. 1981; 47:1963-5. [IDIS 177060] [PubMed 6261930]

66. Koranyi L, Gero L. Influence of diphenylhydantoin on the effect of streptozotocin. Br Med J. 1979; 1:127. [PubMed 153776]

67. Chang P, Riggs CE, Scheerer MT et al. Combination chemotherapy with streptozotocin. II. Clinicopharmacologic correlation of augmented adriamycin toxicity caused by streptozotocin. Clin Pharmacol Ther. 1976; 20:611-6. [IDIS 78754] [PubMed 135667]

68. Lokich JJ, Chawla PL, Frei E. 1,3-Bis-(2-chloroethyl)-1-nitrosourea and streptozotocin chemotherapy. Clin Pharmacol Ther. 1975; 17:374-8. [IDIS 52787] [PubMed 123490]

69. Wiggans RG, Woolley PV, Macdonald JS et al. Phase II trial of streptozotocin, mitomycin-C and 5-fluorouracil (SMF) in the treatment of advanced pancreatic cancer. Cancer. 1978; 41:387-91. [IDIS 101904] [PubMed 147131]

70. Seligman M, Bukowski RM, Groppe CW et al. Chemotherapy of metastatic gastrointestinal neoplasms with 5-fluorouracil and streptozotocin. Cancer Treat Rep. 1977; 61:1375-7. [IDIS 95239] [PubMed 201379]

71. Walter RM, Ensinck JW, Ricketts H et al. Insulin and ACTH production by a streptozotocin responsive islet cell carinoma. Am J Med. 1973; 55:667-70. [IDIS 44506] [PubMed 4356098]

72. Cryer PE, Hill GJ II. Pancreatic islet cell carcinoma with hypercalcemia and hypergastrinemia: response to streptozotocin. Cancer. 1976; 38:2217-21. [IDIS 81073] [PubMed 137070]

73. Friesen SR, Stephens RL, Huard GS II. Effective streptozocin therapy for metastatic pancreatic polypeptide apudoma. Arch Surg. 1981; 116:1090-2. [IDIS 137077] [PubMed 6455109]

74. Moertel CG, Douglas HO Jr, Hanley J et al. Treatment of advanced adenocarcinoma of the pancreas with combination of streptozotocin plus 5-fluorouracil and streptozotocin plus cyclophosphamide. Cancer. 1977; 40:605-8. [IDIS 91635] [PubMed 142579]

75. Jaffrey IS. Long-term survival in patients with advanced adenocarcinoma of the pancreas. Cancer Treat Rep. 1980; 64:1391-2. [IDIS 131447] [PubMed 6451290]

76. Zimmerman SE, Smith FP, Schein PS. Chemotherapy of pancreatic carcinoma. Cancer. 1981; 47:1724-8. [IDIS 134690] [PubMed 6456058]

77. Bukowski RM, Abderhalden RT, Hewlett JS et al. Phase II trial of streptozotocin, mitomycin-C, and 5-fluorouracil in adenoma of the pancreas. Cancer Clin Trials. 1980; 3:321-4. [PubMed 6448716]

78. Moertel CG, Engstrom P, Lavin PT et al. Chemotherapy of gastric and pancreatic carcinoma. Surgery. 1979; 85:509-13. [PubMed 155322]

79. Hayes JR, O’Connell N, O’Neill T et al. Successful treatment of a malignant gastrinoma with streptozotocin. Gut. 1976; 17:285-8. [IDIS 70012] [PubMed 178577]

80. Stadil F, Stage G, Rehfeld JF et al. Treatment of Zollinger-Ellison syndrome with streptozotocin. N Engl J Med. 1976; 294:1440-2. [IDIS 61491] [PubMed 131910]

81. Ruffner BW Jr. Chemotherapy for malignant Zollinger-Ellison tumors: successful treatment with streptozocin and fluorouracil. Arch Intern Med. 1976; 136:1032-4. [IDIS 72624] [PubMed 134679]

82. Huard GS II, Stephens RL, Friesen SR. Zollinger-Ellison syndrome: streptozotocin therapy for metastatic gastrinomas. J Kans Med Soc. 1981; 82:216-21. [PubMed 6453914]

83. Sadoff L, Franklin D. Streptozotocin in the Zollinger-Ellison syndrome. Lancet. 1975; 2:504-5. [IDIS 54464] [PubMed 51317]

84. McGill DB, Miller LJ, Carney JA et al. Hormonal diarrhea due to pancreatic tumor. Gastroenterology. 1980; 79:571-82. [PubMed 6253348]

85. Siegel SR, Muggia FM. Treatment of “pancreatic cholera”. N Engl J Med. 1975; 293:198. [IDIS 52613] [PubMed 166314]

86. Gagel RF, Costanza ME, DeLellis RA et al. Streptozocin-treated Verner-Morrison syndrome: plasma vasoactive intestinal peptide and tumor responses. Arch Intern Med. 1976; 136:1429-35. [IDIS 81199] [PubMed 187136]

87. Biliotti G, Masi C, Macchini M et al. Effects of streptozotocin in the WDHA syndrome not amenable to radical surgery. J Endocrinol Invest. 1980; 3:297-300.

88. Granuci P, Mahler RJ. Streptozotocin treatment of a juvenile onset type diabetic patient with Verner-Morrison syndrome and multi hormonal probable malignant islet cell carcinoma with liver metastases. Horm Metab Res. 1982; 14:327-8. [PubMed 6288539]

89. Kahn CR, Levy AG, Gardner JD et al. Pancreatic cholera: beneficial effects of treatment with streptozotocin. N Engl J Med. 1975; 292:941-5. [IDIS 50430] [PubMed 163965]

90. Kemeny N, Yagoda A, Braun D Jr et al. Therapy for metastatic colorectal carcinoma with a combination of methyl-CCNU, 5-fluorouracil, vincristine and streptozotocin (MOF-Strep). Cancer. 1980; 45:876-81. [IDIS 112171] [PubMed 7260839]

91. Bloom SR, Long RG, Bryant MG et al. Clinical biochemical and pathological studies on 62 vipomas. Gastroenterology. 1980; 78:1143.

92. Feldman JM, Quickel KE, Marecek RL et al. Streptozotocin treatment of metastatic carcinoid tumors. South Med J. 1972; 65:1325-7. [IDIS 29435] [PubMed 4263638]

93. Legha SS, Valdivieso M, Nelson RS et al. Chemotherapy for metastatic carcinoid tumors: experiences with 32 patients and a review of the literature. Cancer Treat Rep. 1977; 61:1699-1703. [IDIS 123176] [PubMed 597818]

94. Moertel CG, Hanley JA. Combination chemotherapy trials in metastatic carcinoid tumor and the malignant carcinoid syndrome. Cancer Clin Trials. 1979; 2:327-34. [PubMed 93982]

95. Vinciguerra V, Coleman M, Jarowski CI et al. A new combination chemotherapy for resistant Hodgkin disease. JAMA. 1977; 237:33-5. [IDIS 67290] [PubMed 62854]

96. Diggs CH, Wiernik PH, Sutherland JC. Treatment of advanced untreated Hodgkin’s disease with SCAB—an alternative to MOPP. Cancer. 1981; 47:224-8. [IDIS 130776] [PubMed 6161689]

97. Hamilton BPM, Cheikh IE, Rivera LE. Attempted treatment of inoperable pheochromocytoma with streptozocin. Arch Intern Med. 1977; 137:762-5. [IDIS 86491] [PubMed 141242]

98. Feldman JM. Treatment of metastatic pheochromocytoma with streptozocin. Arch Intern Med. 1983; 143:1799-1800. [IDIS 175441] [PubMed 6225404]

99. Danforth DN Jr, Triche T, Doppman JL et al. Elevated plasma proglucagon-like component with a glucagon-secreting tumor: effect of streptozotocin. N Engl J Med. 1976; 295:242-5. [IDIS 61935] [PubMed 180408]

100. Khandekar JD, Oyer D, Miller HJ et al. Neurologic involvement in glucagonoma syndrome: response to combination chemotherapy with 5-fluorouracil and streptozotocin. Cancer. 1979; 44:2014-6. [IDIS 109368] [PubMed 228832]

101. Kahn CR, Rosen SW, Weintraub BD et al. Ectopic production of chorionic gonadotropin and its subunits by islet-cell tumors: a specific marker for malignancy. N Engl J Med. 1977; 297:565-9. [PubMed 196194]

102. Marynick SP, Fagadau WR, Duncan LA. Malignant glucagonoma syndrome: response to chemotherapy. Ann Intern Med. 1980; 93:453-4. [IDIS 119909] [PubMed 6254416]

103. DeWys WD, Stoll R, Au W et al. Effects of streptozotocin on an islet cell carcinoma with hypercalcemia. Am J Med. 1973; 55:671-6. [IDIS 44507] [PubMed 4356099]

104. Pipeleers D, Somers G, Gepts W et al. Plasma pancreatic hormone levels in a case of somatostatinoma: diagnostic and therapeutic implications. J Clin Endocrinol Metab. 1979; 49:572-9. [PubMed 158032]

105. Lokich J, Anderson N, Rossini A et al. Pancreatic alpha cell tumors: case report and review of the literature. Cancer. 1980; 45:2675-83. [IDIS 114962] [PubMed 6247056]

106. Kessinger A, Foley JF, Lemon HM. Use of DTIC in the malignant carcinoid syndrome. Cancer Treat Rep. 1977; 61:101-2. [IDIS 81993] [PubMed 861955]

107. Levi JA, Wiernik PH, Diggs CH. Combination chemotherapy of advanced previously treated Hodgkin’s disease with streptozotocin, CCNU, adriamycin, and bleomycin. Med Pediatr Oncol. 1977; 3:33-40. [PubMed 65727]

108. Wiernik PH, Longo D, Duffey PL et al. MOPP vs. MOPP alternating with streptozotocin, CCNU, adriamycin and bleomycin (SCAB) for advanced Hodgkin’s disease. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1981; 22:159.

109. Coleman M, Vinciguerra VP, Rafla S et al. Combination chemoimmunotherapy in advanced recurrent Hodgkin’s disease: a randomized study of the Cancer and Leukemia Group B (CALGB). Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1979; 20:428.

110. Carter SK, Comis RL. The integration of chemotherapy into a combined modality approach for cancer treatment. VI. Pancreatic adenocarcinoma. Cancer Treat Rev. 1975; 2:193-214. [PubMed 1104163]

111. Bukowski RM. Randomized comparison of 5FU and mitomycin C (MF) versus 5FU, mitomycin C and streptozotocin (SMF) in pancreatic adenocarcinoma a Southwest Oncology Group study. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1981; 22:453.

112. Horton J, Mittelman A, Taylor SG III et al. Phase II trials with procarbazine (NSC-77213), streptozotocin (NSC-85998), 6-thioguanine (NSC-752), and CCNU (NSC-79037) in patients with metastatic cancer of the large bowel. Cancer Chemother Rep. 1975; 59:330-40.

113. Douglass HO Jr, Lavin PT, Moertel CG. Nitrosoureas: useful agents for the treatment of advanced gastrointestinal cancer. Cancer Treat Rep. 1976; 60:769-80. [IDIS 73436] [PubMed 782699]

114. Falkson G, Moertel CG, Lavin P et al. Chemotherapy studies in primary liver cancer: a prospective randomized trial. Cancer. 1978; 42:2149-56. [IDIS 110301] [PubMed 214218]

115. Ihde DC, Bunn PA, Cohen MH et al. Combination chemotherapy of hepatocellular carcinoma with adriamycin (ADM) and streptozotocin (STZ). Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1979; 20:410.

116. Ihde DC, Cohen MH, Bunn PA et al. Bleomycin, methotrexate, and streptozotocin in epidermal carcinoma of the lung: an active drug combination with major nonhematologic toxicity. Cancer Treat Rep. 1978; 62:155-7. [IDIS 100301] [PubMed 75065]

117. Chang P, Wiernik PH. Combination chemotherapy with adriamycin and streptozotocin. I. Clinical results in patients with advanced sarcoma. Clin Pharmacol Ther. 1976; 20:605-10. [IDIS 78753] [PubMed 135666]

118. Rauchwerger M, Saibil FG, Cowan DH et al. Intra-arterial use of streptozotocin in a case of metastatic malignant gastrinoma. Can Med Assoc J. 1981; 125:1339-41. [IDIS 142846] [PubMed 6459842]

119. Brown RE, Gregg RE, Hood JC. Droperidol treatment of streptozotocin-induced nausea and vomiting. Drug Intell Clin Pharm. 1982; 16:775-6. [IDIS 157659] [PubMed 6216088]

120. Bennett WM, Aronoff GR, Morrison G et al. Drug prescribing in renal failure: dosing guidelines for adults. Am J Kidney Dis. 1983; 111:155-93.

121. National Cancer Institute. NCI investigational drugs. NIH Publ. No. 80-2141. Washington, DC: US Government Printing Office; 1980:70-2.

122. Reviewers’ comments (personal observations); 1984 May.

123. Upjohn Company. Data on file. Kalamazoo, MI.

124. Johansson EB, Tjalve H. Studies on the tissue-disposition and fate of [14C] streptozocin with special reference to the pancreatic islets. Acta Endocrinol. 1978; 89:339-51. [PubMed 151471]

125. Johansson EB, Tjalve H. The fate of [14C] streptozocin in nicotinamide-pretreated mice: observations on pancreatic islet radioactivity and urinary N′-methyl-[14C] nicotinamide excretion. Cancer Lett. 1979; 8:169-76. [PubMed 162367]

126. Sills JM, Cohon MS. Zanosar sterile powder (streptozocin, streptozotocin) pharmacokinetic profile. Upjohn Company, Kalamazoo, MI; 1983 Apr.

127. Smith FP, Ellenberg SS, Mayer RJ et al. Phase II study of MOF-Strep (methyl-CCNU), vincristine, 5-fluorouracil, streptozotocin) in advanced measurable colorectal carcinoma. A GITSG trial. Proc Annu Meet Am Soc Clin Oncol. 1982; 23:149.

128. Buroker T, Moertel C, Fleming T et al. A randomized comparison of 5-FU containing drug combinations with 5-FU alone in advanced colorectal carcinoma. Proc Am Soc Clin Oncol. 1984; 3:138.

129. Coltman CA Jr. Chemotherapy of advanced Hodgkin’s disease. Semin Oncol. 1980; 7:155-73. [PubMed 7003716]

130. Streuli RA, Ultmann JE. The cure of disseminated Hodgkin’s disease: prospects and problems. Ann Intern Med. 1980; 93:693-5.

131. Santoro A, Bonfante V, Bonadonna G. Salvage chemotherapy with ABVD in MOPP-resistant Hodgkin’s disease. Ann Intern Med. 1982; 96:139-43. [IDIS 153845] [PubMed 6174060]

132. Gurwich EL (Upjohn Company, Kalamazoo, MI): Personal communication; 1984 Jun 12.

133. Reviewers’ comments (personal observations); 1984 Jun.

134. Garnick MB, Ernst T, Martinez F. Acute febrile reaction to streptozocin. N Engl J Med. 1984; 311:798. [IDIS 189747] [PubMed 6236370]

135. Delaney V, de Pertuz Y, Nixon D et al. Indomethacin in Streptozocin-induced nephrogenic diabetes insipidus. Am J Kidney Dis. 1987; 9:79-83. [PubMed 2949606]

136. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]

137. Kris MG, Hesketh PJ, Somerfield MR et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol. 2006; 24:2932-47. [PubMed 16717289]

a. AHFS drug information 2007. McEvoy GK, ed. Streptozocin. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1180-4.

b. Sicor Pharmaceuticals, Inc. Zanosar (streptozocin sterile powder) prescribing information. Irvine, CA; 2003 May.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1509-10.

Advanced Breast Cancer: Learn about treatments to improve quality of life. Click Here

Close
Hide
(web5)