Streptozocin (Zanosar) - Uses, Dose, Side effects

Streptozocin is a chemotherapy medication used to treat certain types of cancer, particularly pancreatic islet cell cancer (pancreatic neuroendocrine tumors) and some types of pancreatic cancer. It is an antibiotic compound originally derived from Streptomyces achromogenes, a type of bacteria.

Streptozocin works by interfering with the DNA of rapidly dividing cancer cells, ultimately leading to their destruction. It is administered as an intravenous (IV) infusion and is typically given in a hospital or clinical setting by a healthcare provider experienced in chemotherapy.

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 can make you feel very nauseous and cause vomiting.
  • To prevent this, doctors recommend taking anti-nausea medications along with Streptozocin.
  • These medications help you avoid feeling sick to your stomach and throwing up.

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

  • First 5 days: Give 1,000 mg of Streptozocin each day through IV (This is called cycle 1).
  • After that: Give 2,000 mg of Streptozocin on the first day of each 3-week period. Continue this until the cancer gets worse or side effects become too severe. This is given alongside another medicine called mitotane.

Streptozocin Dose in the treatment of Gastrointestinal neuroendocrine tumors:

For treating Gastrointestinal neuroendocrine tumors (which is not the common use):

  • Method from Sun 2005:
    • Give 500 mg/m^2 of Streptozocin through IV each day for 5 days.
    • Repeat this every 10 week.
    • Use this in combination with another drug called fluorouracil.
    • Continue until the tumor gets worse or there are serious side effects.
  • Method from Turner 2010:
    • Give 1,000 mg/m^2 of Streptozocin through IV once every 3 weeks.
    • Do this for 3 times (3 cycles). If the tumor doesn't get worse, you can continue for up to 6 cycles, as long as there aren't serious side effects.
    • Use this together with leucovorin, fluorouracil, and cisplatin.

Streptozocin Dose in the treatment of metastatic pancreatic neuroendocrine tumors:

For treating metastatic Pancreatic neuroendocrine tumors with Streptozocin:

Daily Schedule (Moertel 1992):

  • Give 500 mg/m^2 of Streptozocin through IV each day for 5 days in a row.
  • Repeat every 6 weeks.
  • Combine with either doxorubicin or fluorouracil.
  • Continue until the tumor worsens or there are serious side effects.

Weekly Schedule:

  • Start with 1,000 mg/m^2 of Streptozocin through IV once a week.
  • If no improvements after 2 weeks, you can increase the dose up to a maximum of 1,500 mg/m^2 each week.

Alternate Schedules (off-label dosing):

  • Turner 2010:
    • 1,000 mg/m^2 IV once every 3 weeks, up to 6 cycles.
    • Combine with leucovorin, fluorouracil, and cisplatin.
  • Kouvaraki 2004:
    • 400 mg/m^2 IV on days 1 to 5.
    • Repeat every 4 weeks.
    • Use alongside fluorouracil and doxorubicin.
    • Continue until tumor gets worse or side effects are too severe.
  • Dilz 2015:
    • 500 mg/m^2 IV on days 1 to 5.
    • Repeat every 5 or 6 weeks.
    • Combine with fluorouracil.
    • Can continue for up to 1 year if the tumor remains stable.

Streptozocin Dose in Childrens

Not indicated 

Pregnancy Risk Category: D

  • Tests on animals have shown some negative effects related to reproduction.

Use of streptozocin during lactation

  • We don't know if streptozocin gets into breast milk.
  • But to be safe and avoid possible harm to the baby, it's best not to breastfeed while using this drug.

Streptozocin Dose in Kidney Disease:

  • The company that makes the medicine doesn't give specific dosage changes for people with kidney issues.
  • However, doctors should think about the benefits and risks, especially for patients who already have kidney problems.

Based on recommendations from a 2007 study:

  • If kidneys work pretty well (CrCl >50 mL/minute): Use the regular dose.
  • If kidneys work a bit slower (CrCl 10 to 50 mL/minute): Use 75% of the regular dose.
  • If kidneys work much slower (CrCl <10 mL/minute): Use half (50%) of the regular dose.

Streptozocin Dose in Liver disease:

Before treatment for those with liver problems:

  • The company that makes the drug doesn't give specific instructions on changing the dose for people with liver issues.
  • But, since the liver quickly processes streptozocin, be careful when using it.

If liver damage occurs during treatment:

  • The dose might need to be lowered or the treatment might need to be stopped altogether.

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 company that makes the drug hasn't listed any specific reasons not to use it.

Warnings and precautions

Suppression of bone marrow

  • Warning: There's a risk of harm to the blood-making cells.
  • Some people might have a decrease in blood cells, mainly causing mild anemia.
  • Check blood levels every week.
  • If problems arise, you might need to reduce the dose or stop the treatment.

CNS effects

  • This medicine might cause confusion, tiredness, or sadness.
  • Tell patients to be careful doing things like driving or using heavy machines, as their thinking might be affected.

Extravasation/tissue irritation

  • Streptozocin can irritate and possibly damage the skin or tissue if it leaks out of the vein.
  • Make sure it doesn't spill outside the vein.
  • If it does cause irritation like redness, swelling, or tenderness, it usually gets better in a few days.

Gastrointestinal events [US Boxed Warning]

  • Warning: This medicine can cause diarrhea.
  • It can also lead to strong feelings of nausea and vomiting.
  • Because it has a high chance of making you feel sick, taking other medicines to prevent this sickness is recommended.

Glucose intolerance

  • This medicine can cause changes in blood sugar levels.
  • Some people might have mild to medium increases in blood sugar, but this usually goes back to normal.
  • In some cases, it can also lead to very low blood sugar, which is called insulin shock.

Hepatotoxicity: [US Boxed Warning]

  • Warning: This medicine can harm the liver.
  • Signs of this include increased liver enzymes or low levels of a protein called albumin.
  • Check the liver's health every week.
  • If the liver shows signs of damage, you might need to reduce the dose or stop the treatment.

Renal toxicities: [US Boxed Warning]

  • Warning: This medicine can harm the kidneys, especially when the dose adds up over time.
  • It can be very severe or even deadly.
  • Kidney problems might show as increased waste in the blood, no urine production, low phosphorus levels, sugar in the urine, and kidney acid issues.
  • To reduce the risk, make sure to drink enough fluids.
  • Check kidney function and electrolytes before, during, and after each treatment.
  • If you find even a little protein in the urine, do a 24-hour urine test.
  • Avoid using it with other drugs that harm the kidneys.
  • Be cautious if you already have kidney issues.

Secondary malignancy: [US-Boxed Warning]

  • Warning: Streptozocin can cause genetic changes.
  • When given as an injection, it has caused tumors and cancer in animals.

Streptozocin: Drug Interaction

Risk Factor C (Monitor therapy)

Chloramphenicol (Ophthalmic

May enhance the adverse/toxic effect of Myelosuppressive Agents.

CloZAPine

Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.

Coccidioides immitis Skin Test

Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.

Denosumab

May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.

Mesalamine

May enhance the myelosuppressive effect of Myelosuppressive Agents.

Ocrelizumab

May enhance the immunosuppressive effect of Immunosuppressants.

Pidotimod

Immunosuppressants may diminish the therapeutic effect of Pidotimod.

Promazine

May enhance the myelosuppressive effect of Myelosuppressive Agents.

Siponimod

Immunosuppressants may enhance the immunosuppressive effect of Siponimod.

Tertomotide

Immunosuppressants may diminish the therapeutic effect of Tertomotide.

Trastuzumab

May enhance the neutropenic effect of Immunosuppressants.

Risk Factor D (Consider therapy modification)

Baricitinib

Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.

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.

Echinacea

May diminish the therapeutic effect of Immunosuppressants.

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).

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.

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.

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.

Nivolumab

Immunosuppressants may diminish the therapeutic effect of Nivolumab.

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.

Roflumilast

May enhance the immunosuppressive effect of Immunosuppressants.

Sipuleucel-T

Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T 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.

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.

Risk Factor X (Avoid combination)

BCG (Intravesical)

Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).

BCG (Intravesical)

Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).

Cladribine

May enhance the immunosuppressive effect of Immunosuppressants.

Cladribine

May enhance the myelosuppressive effect of Myelosuppressive Agents.

Dipyrone

May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased

Natalizumab

Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.

Pimecrolimus

May enhance the adverse/toxic effect of Immunosuppressants.

Tacrolimus (Topical)

May enhance the adverse/toxic effect of Immunosuppressants.

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.

Monitoring parameters:

Kidney Checks:

  • At the Start, Every Week During Treatment, and 4 Weeks After:
    • BUN test
    • Serum creatinine test
    • Regular urinalysis
    • Blood electrolyte levels
  • If Protein is Found in Urine:
    • Do a 24-hour urine collection

Liver Checks:

  • Every Week:
    • Liver function tests

Blood Checks:

  • Every Week:
    • Full blood count
    • Check for types of white blood cells (differential)
    • Platelet count
    • Blood sugar levels

During Treatment:

  • Keep an eye on where the medicine is injected.

How to administer Streptozocin?

Nausea and Vomiting:

  • Streptozocin can strongly cause nausea and vomiting.
  • To prevent this, take medicines that stop vomiting (antiemetics).

How to Administer:

  • Can be given quickly as a direct IV shot.
  • Or, can be given as a short or long drip (infusion).

Be Careful of Leaks:

  • Streptozocin can irritate or harm the skin if it leaks out.
  • Make sure the needle or tube is properly placed before and during the drip to prevent leaks (extravasation).

What to Do if It Leaks (Extravasation Management):

  • If it starts leaking:
    • Stop the drip right away and disconnect, but leave the needle or tube in.
    • Gently try to suck out the leaked medicine (don't flush the tube).
    • Then, remove the needle or tube and lift up the body part where it leaked.

Mechanism of action of Streptozocin (Zanosar):

  • Streptozocin stops cells from making new DNA by attaching and connecting the DNA strands together.
  • It might also change some proteins.
  • It can affect cells at any point in their growth cycle.

How Quickly It Works:

  • With a dose of 1,500 mg/m^2 every week:
    • Starts working: 17 days after first dose.
    • Strongest effect: 35 days after first dose.

Where It Goes in the Body:

  • Mostly found in the liver, kidneys, and specific cells in the pancreas.

How the Body Breaks It Down:

  • It's processed quickly, mainly by the liver.

How Long It Stays in the Body:

  • Half of it is gone in less than 1 hour.

How It Leaves the Body:

  • Mainly leaves through urine, both as the original drug and its breakdown products.

International Brands of Streptozocin:

  • Zanosar

Streptozocin Brand Names in Pakistan:

You can check for availability and prices by clicking the WhatsApp link here: https://wa.me/message/HV6M3JGTA6RJB1

Comments

NO Comments Found