Streptozocin (Zanosar) is an antineoplastic antibiotic that inhibits DNA synthesis in bacterial and mammalian cells. It is particularly toxic to the islet cells of the pancreas.

Streptozocin Uses:

• Pancreatic neuroendocrine tumors:

  • Treatment of metastatic islet cell carcinoma of the pancreas (symptomatic or progressive disease)

• Off Label Use of Streptozocin in Adults:

  • Adrenocortical carcinoma, metastatic
  • Gastrointestinal neuroendocrine tumors

Streptozocin Dose in Adults

Note:

• Streptozocin is associated with high emetic potential;
• antiemetics are recommended in order to prevent nausea and vomiting.

Streptozocin Dose in the treatment of metastatic Adrenocortical carcinoma (off-label):

• 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).

Streptozocin Dose in the treatment of Gastrointestinal neuroendocrine tumors:

• IV: 500 mg/m² on days 1 to 5 every 10 weeks (in combination with fluorouracil) until disease progression or unacceptable toxicity 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).

Streptozocin Dose in the treatment of metastatic pancreatic neuroendocrine tumors:

• Daily schedule:

  • 500 mg/m² IV once daily for 5 consecutive days every 6 weeks (in combination with either doxorubicin or fluorouracil) till disease progression or unacceptable toxicity/side effects.

• Weekly schedule:

  • 1,000 mg/m² once weekly;
  • if therapeutic response not achieved after 2 weeks, may escalate the dose to a maximum of 1,500 mg/m² weekly

• Alternate schedules (off-label dosing):

  • 1,000 mg/m once every 3 weeks for up to 6 cycles (in combination with leucovorin, fluorouracil, and cisplatin) or
  • 400 mg/m days 1 to 5 every 4 weeks (in combination with fluorouracil and doxorubicin) until disease progression or unacceptable toxicity.
  • or 500 mg/m² on days 1 to 5 every 5 or 6 weeks (in combination with fluorouracil) for up to 1 year if the best response is a stable disease.

Streptozocin Dose in Childrens

Not indicated 

Pregnancy Risk Category: D

• In animal reproduction studies, adverse events were reported.

Use of streptozocin during lactation

• It is unknown if breast milk contains streptozocin.
• Breastfeeding is not recommended due to the risk of serious adverse reactions in breastfed babies.

Streptozocin Dose in Kidney Disease:

• The drug manufacturer's labeling does not include any dosage adjustments.
• However, patients with preexisting kidney impairment should use their clinical judgment to weigh the benefit against the risk of developing renal toxicity.

• These dosing adjustments were recommended by Aronoff 2007, based on an average dose of 500mg/m2.

• • CrCl >50 mL/minute:

    • No dosage adjustment is necessary.

  • CrCl 10 to 50 mL/minute:

    • Administer 75% of dose

  • CrCl <10 mL/minute:

    • Administer 50% of dose

Streptozocin Dose in Liver disease:

• Hepatic impairment prior to treatment:

  • There are no dosage adjustments provided in the drug manufacturer’s labeling.
  • However, streptozocin is rapidly hepatically metabolized; use with caution.

• Hepatotoxicity during treatment:

  • May require dosage reduction or discontinuation.

Streptozocin (Zanosar) Side effects:

• 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

Contraindications to Streptozocin (Zanosar):

• The manufacturer's labeling does not contain any contraindications.

Warnings and precautions

• Suppression of bone marrow

  • [US Boxed Warning] Hematologic toxicities have been reported.
    • Rarely, mild bone marrow suppression may occur.
    • Monitor blood counts every week.
    • You may need to reduce or stop taking the medication.

• CNS effects

  • Can cause confusion, lethargy, or depression.
  • Patients should be cautioned about tasks that require mental alertness, such as driving or operating machinery.

• Extravasation/tissue irritation

  • Streptozocin, an irritant that has vesicant-like characteristics, is called Streptozocin.
  • Avoid excessive use.
  • Although local tissue irritation and inflammation (edema, burning, tenderness, etc.) can occur, it usually disappears in a few days.

• Gastrointestinal events [US Boxed Warning]

  • It has been reported that there is diarrhea.
  • Can cause nausea and vomiting.
  • Streptozocin has a high emetic potency. Antiemetics are recommended for nausea and vomiting (Dupuis 2011, Hesketh 2017, Roila 2016).

• Glucose intolerance

  • It is possible to have mild-to-moderate sugar intolerance; however, it can be reversed.
  • It has been shown that insulin shock can be caused by hypoglycemia.

• Hepatotoxicity: [US Boxed Warning]

  • It has been reported that liver dysfunction is common.
  • Hypoalbuminemia and elevated transaminases may indicate hepatotoxicity.
  • Monitor liver function every week.
  • You may need to reduce or stop taking the medication for liver dysfunction.

• Renal toxicities: [US Boxed Warning]

  • Dose-related and cumulative renal toxicities can be severe or fatal.
  • Reports of anuria and hypophosphatemia, azotemia, glyuria, and renal tubular acidsosis include anuria, anuria, hypophosphatemia, azaotemia, and glycosuria.
  • A good hydration can reduce the risk of developing nephrotoxicity.
  • Monitor renal function (BUN and serum creatinine and serial urinalysis), and electrolytes before, during, and after each treatment.
  • Mild proteinuria can be an indicator of kidney toxicity. If proteinuria is confirmed by urinalysis or other methods, you should have 24-hour urine collection.
  • Use this medication only in combination with other nephrotoxic drugs.
  • Patients with preexisting kidney disease should be cautious.

• Secondary malignancy: [US-Boxed Warning]

  • Streptozocin can cause mutations in the body; its parenteral use can be tumorigenic or carcinogenic to animals.

Streptozocin: Drug Interaction

Monitoring parameters:

• 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

How to administer Streptozocin?

• IV: Streptozocin is associated with high emetic potential;
• antiemetics are recommended to prevent nausea and vomiting.
• 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.

Mechanism of action of Streptozocin (Zanosar):

• Streptozocin inhibits DNA synthesis by cross-linking and alkylation of the DNA strands, as well as possible protein modification. Cell cycle nonspecific

Onset:

• 1,500 mg/m 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)

International Brands of Streptozocin:

• Zanosar

Streptozocin Brand Names in Pakistan:

No Brands Available in Pakistan.