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Mitomycin (Datisan) Injection - Uses, Dose, Side effects, MOA

Mitomycin (Datisan) or Mitomycin C is one of the oldest chemotherapeutic drugs that is still used in the treatment of advanced gastric, pancreatic, cervical, anal, and vulvar cancer.

Mitomycin (Datisan) Uses:

Gastric cancer:
- It is helpful in the treatment of disseminated adenocarcinoma of the stomach (in combination with other chemotherapy agents) and as a palliative treatment when other modalities have failed.
Pancreatic cancer:
- Treatment of disseminated adenocarcinoma of the pancreas (in combination with other chemotherapy agents) and as a palliative treatment when other modalities have failed.
- Limitations of use: It is not proposed for single-agent primary therapy or to replace appropriate surgery and/or radiotherapy in the treatment of such conditions.
Off Label Use of Mitomycin in Adults:
- Anal cancer
- Bladder cancer
- recurrent or metastatic cervical cancer,
- Advanced esophageal cancer
- Hepatocellular carcinoma (chemoembolization)
- Advanced vulvar cancer

Mitomycin Dose in Adults:

Mitomycin (Datisan) Dose in the treatment of Anal carcinoma (off-label):

The typical dose of mitomycin given through a vein (IV) depends on different treatment plans:

One plan involves giving 10 milligrams of mitomycin per square meter of the person's body surface area as a quick IV injection on days 1 and 29. The most that is given in one dose is 20 milligrams. This is done along with fluorouracil (another chemotherapy drug) and radiation therapy.
Another plan gives 12 milligrams of mitomycin per square meter on day 1 only, also along with fluorouracil and radiation therapy.
Some treatments use a single dose of 15 milligrams of mitomycin per square meter on day 1, along with fluorouracil and radiation therapy.
In combination with a drug called capecitabine and radiation therapy, one approach is to give a dose of 10 milligrams of mitomycin per square meter on day 1, with the maximum dose being 15 milligrams.
Similar to the previous plan, another approach involves a single dose of 12 milligrams of mitomycin per square meter on day 1, but with the maximum dose being 20 milligrams.

These different dosing plans are used in combination with other medications and radiation therapy to treat anal carcinoma.

Mitomycin (Datisan) Dose in the treatment of Bladder cancer (off-label):

In treating bladder cancer, especially when the standard methods might not be applicable, mitomycin is used in ways that are not officially approved for this purpose.

Muscle Invasive Bladder Cancer:

When the cancer has invaded the muscle layer of the bladder, the treatment involves giving 12 milligrams of mitomycin per square meter of the person's body surface on the first day of the treatment.
This is done in combination with fluorouracil (another chemotherapy drug) and radiation therapy.

Nonmuscle Invasive Bladder Cancer: For cases where the cancer hasn't spread to the muscle layer of the bladder, there are different approaches for different levels of risk:

Low Risk of Recurrence (Uncomplicated):
- A single dose of 40 milligrams of mitomycin is put directly into the bladder after surgery. It's left in the bladder for 1 to 2 hours.
Increased Risk of Recurrence:
- One approach is to use 20 milligrams of mitomycin every week for 6 weeks. This is followed by a maintenance phase where 20 milligrams are used monthly for 3 years. The medication is retained in the bladder for 1 to 2 hours.
- Another approach is to use 40 milligrams of mitomycin weekly for 6 weeks. This is done with urine alkalinization (making the urine less acidic) and reducing urine volume to increase the concentration of the drug. The medication is retained in the bladder for 2 hours.

Remember that these dosing plans are used in specific situations and are considered "off-label," meaning they aren't the standard or officially approved treatments.

Mitomycin (Datisan) Dose in the treatment of recurrent or metastatic Cervical cancer:

When dealing with cervical cancer that has come back or spread to other parts of the body, and the standard treatment might not be applicable, mitomycin is sometimes used in ways that aren't officially approved for this purpose.

Recurrent or Metastatic Cervical Cancer:

In this situation, mitomycin can be given through a vein (IV) along with another chemotherapy drug called cisplatin. The dosing is as follows:

A dose of 6 milligrams of mitomycin per square meter of the person's body surface is administered on the first day of a treatment cycle.
This treatment cycle occurs once every 4 weeks.
The combination treatment with mitomycin and cisplatin is repeated for a minimum of 2 cycles. Ideally, it's continued for 9 cycles if possible.

It's important to note that this dosing plan is considered "off-label," which means it's not the standard or officially approved treatment for recurrent or metastatic cervical cancer.

Mitomycin (Datisan) Dose in the treatment of advanced Esophageal cancer, (off-label):

Advanced Esophageal Cancer:

Mitomycin is given intravenously (IV), combined with two other chemotherapy drugs, cisplatin and fluorouracil:

The dosage is 7 milligrams of mitomycin for every square meter of the patient's body surface area.
There's a cap to the dose, so even if calculations based on body surface area exceed 14 milligrams, the patient should not receive more than this 14 mg maximum dose.
This dose is administered once every 6 weeks.
The treatment cycle is repeated for a total of 4 cycles.

It's important to remember that this treatment approach is based on specific studies and isn't the universally accepted standard of care for advanced esophageal cancer.

Mitomycin (Datisan) Dose in the treatment of Gastric cancer:

For treating gastric cancer, which originates in the stomach, mitomycin can be used. Here's a breakdown of the dosing for this type of cancer:

Standard Treatment for Gastric Cancer:

Mitomycin is given intravenously (IV).
The dosage is 20 milligrams of mitomycin per square meter of the patient's body surface area.
This dose is administered once every 6 to 8 weeks.

Off-label Treatment for Gastric Cancer:

Based on specific studies or expert opinions, sometimes drugs are used in a manner that isn't the standard or official treatment. This is what "off-label" means:

Mitomycin is given intravenously (IV) in combination with two other chemotherapy drugs, cisplatin and fluorouracil.
The dosage is 7 milligrams of mitomycin per square meter of the patient's body surface area.
There's a maximum limit to the dose: even if the calculated dosage based on body surface area exceeds 14 milligrams, the patient should not receive more than this 14 mg cap.
This dose is given once every 6 weeks.
The treatment is repeated for a total of 4 cycles.

Mitomycin (Datisan) Dose for chemoembolization in the treatment of Hepatocellular cancer:

For the treatment of hepatocellular cancer (a type of liver cancer) using chemoembolization, mitomycin can be utilized in an off-label manner. Chemoembolization involves delivering chemotherapy drugs directly to the tumor by injecting them into the tumor's blood supply. Here's the dosing information for this application:

Conventional Transcatheter Arterial Chemoembolization (cTACE)

Using the method of cTACE, mitomycin is delivered directly into the artery supplying the tumor:

A single dose of 10 milligrams of mitomycin can be given via intra-arterial injection. Based on the physician's judgment and how the patient responds, this treatment might be repeated at intervals of 6 to 8 weeks (as per Yamada 2019).
Alternatively, the dosage can be calculated based on body surface area, where 8 milligrams of mitomycin per square meter is injected intra-arterially as a single dose. This is repeated every 4 weeks for a minimum of 2 doses (as per Vogl 2012).

For specifics on administration, dosing modifications, and other details, one should refer to the given treatment protocol and policies of the medical institution where the procedure is performed.

Mitomycin (Datisan) Dose in the treatment of Pancreatic cancer:

For the treatment of pancreatic cancer using mitomycin, here's the dosing information:

Pancreatic Cancer Treatment:

Mitomycin is administered intravenously (IV).
The dosage is calculated as 20 milligrams of mitomycin for every square meter of the patient's body surface area.
This dose is given once every 6 to 8 weeks.

It's essential to work closely with a healthcare provider to ensure appropriate dosing and monitor for potential side effects. Regular monitoring is crucial during chemotherapy treatment to assess the effectiveness of the therapy and adjust the treatment plan if necessary.

Mitomycin (Datisan) Dose in the treatment of advanced Vulvar cancer:

For treating advanced vulvar cancer using mitomycin in an off-label manner (which means it's not the official or approved standard for this purpose), here's the dosing information:

Advanced Vulvar Cancer Treatment:

Mitomycin is administered intravenously (IV).
The dosage is calculated as 15 milligrams of mitomycin for every square meter of the patient's body surface area.
This dose is given on the first day and then repeated every 14 days.
The treatment is repeated for a total of 2 cycles.
Along with mitomycin, the treatment includes concurrent radiation and another chemotherapy drug called fluorouracil.

Use in Children:

The safety and efficacy of the drug in children have not been established.

Mitomycin (Datisan) Pregnancy Risk Category: X

Tests on animals have shown that the drug or substance can cause problems during pregnancy.

Use of mitomycin during breastfeeding

We don't know if mitomycin goes into breast milk.
But because it could harm the baby and cause severe problems, the company that makes the drug suggests that breastfeeding isn't a good idea if you're taking mitomycin.

Mitomycin (Datisan) Dose in Kidney Disease:

The company that makes the medicine says don't use it if the patient's serum creatinine level is more than 1.7 mg/dL. However, they don’t give specific advice on changing the dosage based on this. But, based on another source from 2007 (Aronoff), here's what's suggested:

If the kidney's filtration rate (CrCl) is less than 10 mL/minute: Give 75% of the normal dose.
If the patient is on a specific kind of dialysis (CAPD): Give 75% of the normal dose.

Mitomycin (Datisan) Dose in Liver disease:

However, there are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Common Side Effects of Mitomycin (Datisan):

Gastrointestinal:
- Anorexia
- Nausea
- Vomiting
Hematologic & oncologic:
- Bone marrow depression
- Hemolytic-uremic syndrome
- Thrombotic thrombocytopenic purpura
Miscellaneous:
- Fever

Less Common Side Effects of Mitomycin (Datisan):

Dermatologic:
- Alopecia
Gastrointestinal:
- Mucous membrane disease
- Stomatitis
Renal:
- Increased serum creatinine

Contraindications to Mitomycin (Datisan):

Don't use mitomycin if:

You're allergic to it or anything in it.
You have low platelet levels in your blood.
You have blood clotting problems or are more likely to bleed than usual.

Warnings and precautions

Bladder fibrosis, and contraction

Using mitomycin in the bladder (though not the officially recommended way) can sometimes lead to a condition where the bladder becomes scarred and contracts more than normal. This can cause problems.

Suppression of bone marrow: [US Boxed Warning]

Be aware that using mitomycin can cause a problem in the bone marrow where the body makes blood cells.
This can lead to low levels of platelets and white blood cells, which are important for clotting and fighting infections.
This bone marrow issue can be severe and even cause infections that can be fatal.
Usually, the lowest levels of these blood cells happen about 4 weeks after starting the treatment, but it might take up to 8 weeks.
Thankfully, the body usually recovers within 10 weeks.
However, because this is a big concern, you need to keep a close eye on your blood counts while getting treated and for 8 weeks afterward.
Sometimes, the treatment might need to be stopped or the dose changed if platelet levels go below 100,000 or white blood cell levels drop below 4,000, or if these levels keep getting worse.

Extravasation

Mitomycin is very strong and can seriously damage skin and tissue if it leaks out of the vein during the injection.
Before and during the injection, make sure the needle or tube is correctly placed inside the vein.
If it leaks into the surrounding tissue, it can cause skin redness, sores, or even dead tissue.
Some of these effects might not show up immediately but can appear later.

Heart Failure:

The American Heart Association's scientific statement states that mitomycin may cause either reversible or exacerbate underlying myocardial dysfunction (magnitude moderate).

Hemolytic-uremic Syndrome: [US Boxed Warn]

A severe condition called hemolytic-uremic syndrome (HUS) can happen due to mitomycin use.
This syndrome affects the blood, kidneys, and sometimes other parts of the body.
It involves low levels of red blood cells and platelets, and kidney failure that might be irreversible.
This syndrome can happen at any time when using mitomycin, either alone or with other drugs.
It's more likely to occur with higher single doses, especially doses over 60 mg.
Blood transfusions might make HUS symptoms worse.
There are also rare effects like lung swelling, nerve problems, and high blood pressure.
HUS from mitomycin can be very serious, and sometimes it can even be fatal.

Toxicity in the lungs:

There have been cases where mitomycin, especially when used with other drugs, has caused serious lung problems like acute respiratory distress syndrome (ARDS).
This lung issue can happen in patients who get a lot of oxygen (more than half of what they breathe in) during surgery.
It's important to give just enough oxygen to keep blood oxygen levels safe and avoid giving too much fluid.
Another lung problem from mitomycin is difficulty breathing, a dry cough, and abnormal lung images on X-rays.
If someone has these lung issues while on mitomycin and other causes are ruled out, the drug should be stopped.

Renal impairment

If the kidney test result (called serum creatinine) is more than 1.7 mg/dL, don't give mitomycin because it might harm the kidneys.
Always keep an eye on kidney health when using this drug.

Mitomycin(systemic): Drug Interaction

Risk Factor C (Monitor therapy)
Antineoplastic Agents (Vinca Alkaloids)	May enhance the adverse/toxic effect of MitoMYcin (Systemic). Specifically, the risk of pulmonary toxicity may be increased.
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.
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Lumacaftor	May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
P-glycoprotein/ABCB1 Inducers	May decrease the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ranolazine	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Smallpox and Monkeypox Vaccine (Live)	Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live).
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
Lasmiditan	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
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.
Upadacitinib	Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib.
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. Exceptions: Smallpox and Monkeypox Vaccine (Live).

Monitoring parameters:

Blood Tests:
- Check the Complete Blood Count (CBC) with details of different types of blood cells.
- Do this test multiple times while on therapy and keep checking for at least 8 weeks after stopping the therapy.
Kidney Health:
- Check serum creatinine to see how well the kidneys are working.
Lung Health:
- Perform pulmonary function tests to check the lungs' health and function.
Look Out For Specific Symptoms:
- Watch for signs or symptoms of HUS, a severe condition that affects the blood and kidneys.
Infusion Site:
- Keep an eye on the place where the drug is injected to make sure there are no issues or reactions.

How to administer Mitomycin (Datisan)?

IV (Intravenous) Administration:

Give the drug slowly, directly into the vein.
Use a constant flow of saline (saltwater) during this.
It might be best to use a central venous catheter, which is a special tube placed in a large vein.

Handling Leaks (Extravasation):

Mitomycin can damage tissue if it leaks out of the vein.
Always make sure the needle or catheter is correctly placed before and during giving the drug.
If the drug does leak:
- Stop the infusion immediately but leave the needle in place.
- Try to gently pull out the leaked drug without flushing more fluid in.
- Remove the needle and lift up the affected limb.
- Use a treatment called DMSO as soon as possible.
- Place a cold pack on the area for 20 minutes, repeating 4 times a day for 1-2 days.

DMSO Treatment for Leaks:

Put DMSO on the skin, covering double the leaked area.
Apply every 8 hours for 7 days, starting within 10 minutes of the leak.
Don't cover it with a bandage.

Intravesicular (Inside the Bladder) Use:

Pour the drug into the bladder and let it stay there for 1 to 2 hours.
Move the patient every 15 to 30 minutes to ensure even distribution.

Intra-arterial (Inside the Artery) Use in TACE:

For a procedure called TACE, mitomycin can be given with other substances to target the cancer.
The drug is combined with lipiodol and a contrast agent. Then, it's followed by a special material to block the blood vessels.
Patients also get IV antibiotics before the procedure.
The blocking material is injected until the bleeding stops.
Always follow specific protocols and hospital guidelines for this procedure.

Mechanism of action of Mitomycin (Datisan):

What It Does:

Mitomycin changes the structure of DNA by connecting its parts together, especially the parts called guanine and cytosine.
This process stops the creation of new DNA and RNA, which are essential for cells to function and reproduce.

When It Works Best:

Mitomycin isn't picky about a specific time in a cell's life cycle to work best. But, it's most effective against cells that are about to replicate or have just started the process (referred to as late G and early S phases).

This info helps explain how mitomycin works to stop cancer cells from growing and dividing.

Metabolism:

Mitomycin is mainly processed and broken down in the liver.

Half-life Elimination:

About half of mitomycin is removed from the body in approximately 17 minutes after a 30 mg dose. This means the amount of the drug in the body decreases by half during this time.

How It's Removed from the Body: