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Dacarbazine Injection - Uses, Dose, Side effects, MOA, Brands

Dacarbazine, also known by its trade name DTIC-Dome, is a chemotherapy medication used in the treatment of various types of cancer, particularly malignant melanoma and Hodgkin lymphoma. It belongs to the class of alkylating agents, which are used to interfere with the DNA replication process of rapidly dividing cells, ultimately inhibiting their growth and division.

Dacarbazine is often administered intravenously and works by causing damage to the DNA within cancer cells, which leads to the cells' inability to divide and grow. It is commonly used in combination with other chemotherapy drugs or as part of combination therapies for different types of cancer.

Dacarbazine is a chemotherapeutic cytotoxic (non-cell cycle specific) drug that is used to treat patients with hodgkins lymphoma and malignant melanoma in combination with other chemotherapeutic agents.

Dacarbazine Uses:

Hodgkin lymphoma:
- It is used in the management of Hodgkin lymphoma (in combination with other chemotherapeutic agents)
Metastatic malignant melanoma:
- It can be used in the treatment of metastatic malignant melanoma
Use: Off-Label: Adult
- Advanced Medullary thyroid cancer
- Advanced Pancreatic neuroendocrine tumors
- Malignant Pheochromocytoma
- Advanced Soft-tissue sarcomas

Dacarbazine Dose in Adults

Note: Dacarbazine is a medicine used to treat certain types of cancer like skin cancer and a kind of lymph gland cancer. It works by attacking the DNA of cancer cells, stopping them from growing. A big side effect of this medicine is that it can make people feel very sick and want to throw up.

Dacarbazine Dose in the treatment of Hodgkin lymphoma:

When treating Hodgkin lymphoma, Dacarbazine is given as part of two main regimens:

ABVD Regimen:

Dose: 375 mg/m^2 through IV (a way of giving medicine directly into the bloodstream) on days 1 and 15, every 4 weeks.
How long: This is given for 2 to 4 cycles.
With what other drugs: It's given alongside doxorubicin, bleomycin, and vinblastine.

A-AVD Regimen:

Dose: 375 mg/m^2 through IV on days 1 and 15, every 4 weeks.
How long: This is given for up to 6 cycles.
With what other drugs: It's given with brentuximab vedotin, doxorubicin, and vinblastine.
Extra care: A medicine called G-CSF (like filgrastim) is given from the start to help prevent low white blood cell counts.

Dacarbazine Dose in the treatment of metastatic malignant Melanoma:

For treating metastatic malignant melanoma, Dacarbazine is given as:

Dose: 250 mg/m^2 via IV (directly into the bloodstream) over 30 minutes.
When: Once a day from days 1 to 5.
How often: Every 3 weeks.

Dacarbazine Dose in the treatment of stage IIIA-N2a to stage IIIC-N3, high-risk melanoma (off-label dosing/combinations):

For treating high-risk melanoma (stages IIIA-N2a to IIIC-N3) using an off-label combination, Dacarbazine is given as follows:

Dose: 800 mg/m^2 through IV (into the bloodstream) over 1 hour.
When: On day 1.
How often: Every 3 weeks.
With what other drugs: It's given alongside cisplatin, vinblastine, interleukin-2, and interferon alfa-2b.
Duration: This treatment is given for 3 cycles.

Dacarbazine Dose in the treatment of advanced Medullary thyroid cancer (off-label):

For treating advanced medullary thyroid cancer using Dacarbazine (off-label use):

Combination with fluorouracil and streptozocin:
- Dose: 200 mg/m^2 via IV (into the bloodstream).
- When: Every day for 5 days.
- How often: Every 6 weeks.
Combination with cyclophosphamide and vincristine:
- Dose: 600 mg/m^2 via IV.
- When: Once a day for 2 days.
- How often: Every 3 or 4 weeks.
Combination with fluorouracil:
- Dose: 250 mg/m^2 via IV over 15 to 30 minutes.
- When: Every day for 5 days.
- How often: Every 4 weeks.

Dacarbazine Dose in the treatment of advanced Pancreatic neuroendocrine tumors (off-label):

For treating advanced pancreatic neuroendocrine tumors using Dacarbazine (off-label use):

Dose: 850 mg/m^2 given via IV (directly into the bloodstream) over a period of 60 to 90 minutes.
When: On the first day.
How often: Every 4 weeks.

Dacarbazine Dose in the treatment of malignant Pheochromocytoma (off-label):

For treating malignant pheochromocytoma with Dacarbazine (an off-label use):

Dose: 600 mg/m^2 given via IV (into the bloodstream).
When: Once a day for 2 days.
How often: Every 3 or 4 weeks.
With what other drugs: It's used together with cyclophosphamide and vincristine.

Dacarbazine Dose in the treatment of advanced Soft tissue sarcoma (off-label): IV:

For treating advanced soft tissue sarcoma using Dacarbazine (off-label use):

AD Regimen (with doxorubicin):

First option (based on Antman 1993):
- Dose: 250 mg/m^2 per day given via IV as a continuous infusion.
- When: For 4 consecutive days.
- How often: Every 3 weeks.
- Total dose per cycle: 1,000 mg/m^2.
Second option (based on Zalupski 1991):
- Dose: 187.5 mg/m^2 per day given via IV as a continuous infusion.
- When: For 4 consecutive days.
- How often: Every 3 weeks.
- Total dose per cycle: 750 mg/m^2.

MAID Regimen (with mesna, doxorubicin, and ifosfamide):

Dose: 250 mg/m^2 per day via IV as a continuous infusion.
When: For 4 consecutive days.
How often: Every 3 weeks.
Total dose per cycle: 1,000 mg/m^2.

Dacarbazine Dose in Childrens

Note:

If Dacarbazine is being used for cancer treatment, especially when used with other medications, you should also check the dosing details for those combinations.
Dacarbazine, regardless of the dose, can make people feel very sick and prone to throwing up.

Dacarbazine Dose in the treatment of High-Risk Hodgkin lymphoma: Limited data available:

For high-risk Hodgkin lymphoma in kids and teenagers:

Using the ABVD regimen (based on limited data):

Dose: They get 375 mg/m^2 of Dacarbazine through an IV (a drip into the bloodstream).
How long it takes: It's given over 30 to 60 minutes.
When: On the first and fifteenth days of a 28-day treatment cycle.
How many times: This is done for 2 to 6 cycles.
With other medicines: It's given together with doxorubicin, vinblastine, and bleomycin.

Dacarbazine Dose in the treatment of High-risk Melanoma: Limited data available:

For high-risk melanoma in kids aged 10 and older and in teenagers:

Based on limited data:

Dose: They get 800 mg/m^2 of Dacarbazine through an IV (a drip into the bloodstream).
How long it takes: It's given over 1 hour.
When: On the first day, but only after they've been given vinblastine.
How often: Every 21 days.
How many times: This is done for 3 cycles.
With other medicines: It's used with cisplatin and interferon alfa-2b.

Pregnancy Risk Factor C

Dacarbazine has a warning because studies in animals suggest it might cause cancer or birth defects. Pregnant women or those who could become pregnant should avoid this treatment. If cancer is found during pregnancy, experts recommend getting care from a team of specialists, including an oncologist, an obstetrician, and more.

If chemotherapy is needed during pregnancy, guidelines suggest:

Avoiding it during the first trimester.
Leaving a 3-week gap between the last chemo dose and the expected delivery.
Not giving chemotherapy beyond a certain point in pregnancy.

For Hodgkin lymphoma treatment during pregnancy:

Early-stage: ABVD treatment can be given safely later in pregnancy.
Advanced-stage: ABVD can be given in the later stages of pregnancy.

Use of dacarbazine while breastfeeding

We don't know if dacarbazine gets into breast milk.
Because it might harm a breastfeeding baby, a decision should be made: either stop taking dacarbazine or stop breastfeeding.
This choice should consider the benefits of the treatment for the mother.

Dacarbazine Dose in Kidney disease:

The maker of dacarbazine doesn't give specific dosage changes for kidney function. But based on a study from 1995 (by Kintzel), here are suggested adjustments:

If your kidney function (CrCl) is 46 to 60 mL/minute: Take 80% of the regular dose.
If CrCl is 31 to 45 mL/minute: Take 75% of the regular dose.
If CrCl is 30 mL/minute or less: Take 70% of the regular dose.

Dacarbazine Dose in Liver disease:

The company that makes the drug doesn't give guidance on changing the dose.
But the drug might harm the liver, so it's important to watch out for signs of liver damage.

Side effects of Dacarbazine:

Central nervous system:
- Infusion-site pain
Dermatologic:
- Alopecia
Gastrointestinal:
- Nausea and vomiting
- Anorexia
Hematologic & oncologic:
- Bone marrow depression
- Leukopenia
- Thrombocytopenia

Contraindications to Dacarbazine:

Don't use dacarbazine if you're really sensitive to it or any parts of it.

In Canada, it's also not recommended if you had serious bone marrow problems before.

Warnings and precautions

Anaphylaxis

After taking dacarbazine, there's a risk of a severe allergic reaction called anaphylaxis. It's important to be aware and get medical help immediately if this happens.

Suppression of bone marrow: [US Boxed Warning]

Taking dacarbazine can affect your bone marrow, leading to low levels of white blood cells (leukopenia), low platelets (thrombocytopenia), and sometimes anemia.
These problems can be severe and might lead to treatment pauses or stops.
Keep an eye on your blood counts (CBC with differential) as advised by your doctor.
Leukopenia typically starts around 2 weeks after taking the drug, lasting about 1 to 3 weeks.
Thrombocytopenia starts about 2.5 weeks after, also lasting 1 to 3 weeks.

[US Boxed Warning] Carcinogenic/teratogenic

There's a warning for dacarbazine because animal studies show it might cause cancer or birth defects.
This means there are potential risks, especially during pregnancy.

Extravasation

If dacarbazine leaks out of the vein and into the surrounding tissue (called extravasation), it can cause skin irritation, damage, and a lot of pain.
It's important to make sure the medicine is going into the vein properly.

Gastrointestinal toxicities:

Dacarbazine can make people feel very sick and want to throw up.
It's recommended to take medicines that help prevent this nausea and vomiting when using dacarbazine.

Hepatic effects: [US Boxed Warning]

There's a warning for dacarbazine because it can seriously damage the liver, leading to liver cell death.
This liver damage can be very dangerous and sometimes even fatal.
While the damage is more common when dacarbazine is used with other cancer drugs, it can also happen when dacarbazine is used on its own.

Hepatic impairment

If someone has liver problems, be careful when using dacarbazine.
The drug stays in the body longer in such cases, which could increase the risk of side effects.
It might be necessary to give a lower dose.

Renal impairment

For people with kidney issues, using dacarbazine might be risky.
The drug can stay in the body longer, increasing the chance of side effects.
It could be necessary to use a smaller dose.

Dacarbazine: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Abiraterone Acetate	High risk of Inhibitors causing an increase in serum CYP1A2 Substrates concentrations
Broccoli	High risk of Inducers causing a decrease in serum CYP1A2 Substrates concentrations
Cannabis	High risk of Inducers causing a decrease in serum CYP1A2 Substrates concentrations
Chloramphenicol Ophthalmic	May increase the toxic/adverse effects of Myelosuppressive Agents.
CloZAPine	CloZAPine's toxic/adverse effects may be exacerbated by myelosuppressive agents. Particularly, there may be an increase in the risk of neutropenia.
Coccidioides immitis skin test	Coccidioides immitis Skin Test may be affected by immunosuppressants.
Moderate CYP1A2 Inhibitors	Might decrease metabolism of CYP1A2 substrates (High Risk with Inhibitors).
Cyproterone	High risk of Inducers causing a decrease in serum CYP1A2 Substrates concentrations
Deferasirox	High risk of Inhibitors causing an increase in serum CYP1A2 Substrates concentrations
Obeticholic Acid	High risk of Inhibitors causing an increase in serum CYP1A2 Substrates concentrations
Ocrelizumab	May increase the immunosuppressive effects of Immunosuppressants.
Peginterferon Al-2b	High risk of Inhibitors causing an increase in serum CYP1A2 Substrates concentrations
Pidotimod	Pidotimod's therapeutic effects may be diminished by immunosuppressants.
Promazine	May increase the myelosuppressive effects of Myelosuppressive Drugs.
Siponimod	Siponimod's immunosuppressive effects may be enhanced by taking immunosuppressants.
Sipuleucel - T	Sipuleucel T's therapeutic effects may be diminished by immunosuppressants
SORAfenib	Could lower the serum level of dacarbazine. The active metabolite of dacarbazine may be increased by Sorafenib.
Teriflunomide	High risk of Inducers causing a decrease in serum CYP1A2 Substrates concentrations
Tertomotide	Tertomotide's therapeutic effects may be diminished by immunosuppressants.
Trastuzumab	May increase the neutropenic effects of Immunosuppressants.
Risk Factor D (Consider therapy modifications)
Baricitinib	Baricitinib's immunosuppressive effects may be enhanced by immunosuppressants. Baricitinib should not be used in combination with immunosuppressants like azathioprine and cyclosporine. It is permissible to use methotrexate antirheumatically or nonbiologic disease-modifying antirheumatic drug (DMARDs), concurrently.
Strong CYP1A2 Inhibitors	Might decrease metabolism of CYP1A2 substrates (High Risk with Inhibitors).
Echinacea	Might decrease the therapeutic effects of Immunosuppressants.
Fingolimod	Fingolimod may be immunosuppressed by immunosuppressants. When possible, avoid the use of fingolimod with other immunosuppressants. Patients should be closely monitored for any additive immunosuppressant effects, such as infections, if they are used together.
Fotemustine	Dacarbazine may have an adverse/toxic effect that can be increased. In particular, there may be an increase in the risk of pulmonary toxicities (adult acute respiratory distress syndrome). Management: Avoid taking fotemustine or dacarbazine at the same time, especially if you are taking high doses. Between the last dose fotemustine dose and the first dose decadrone, a gap of one week should be allowed.
Leflunomide	Leflunomide's toxic/adverse effects may be exacerbated by immunosuppressants. The risk of hematologic toxicities such as pancytopenia and thrombocytopenia (agranulocytosis) may increase. Patients on immunosuppressants should not be given a leflunomide loading dosage. Patients who are receiving leflunomide or another immunosuppressant must be checked for bone marrow suppression at minimum monthly.
Lenograstim	Antineoplastic Agents can reduce the therapeutic effects of Lenograstim. Management: Lenograstim should be avoided 24 hours prior to and 24 hours following the completion of myelosuppressive, cytotoxic chemotherapy.
Lipegfilgrastim	Antineoplastic agents may reduce the therapeutic effects of Lipegfilgrastim. Management: It is important to avoid the simultaneous use of lipegfilgrastim with myelosuppressive, cytotoxic chemotherapy. After myelosuppressive chemotherapy has been completed, lipegfilgrastim must be given at least 24 hours.
Nivolumab	Nivolumab's therapeutic effects may be diminished by immunosuppressants.
Palifermin	Can increase the toxic/adverse effects of Antineoplastic Agents. In particular, oral mucositis can be more severe and prolonged. Management: Avoid palifermin administration within the first 24 hours of infusion or 24 hours following myelotoxic chemotherapy.
Roflumilast	May increase the immunosuppressive effects of Immunosuppressants.
Tofacitinib	Tofacitinib's immunosuppressive effects may be enhanced by immunosuppressants. Management: It is permissible to use methotrexate (or nonbiologic disease-modifying antirheumatic drug (DMARDs), concurrently with antirheumatic doses. This warning appears to be particularly targeted at more potent immunosuppressants.
Vaccines (Inactivated).	Immunosuppressants can reduce the therapeutic effects of Vaccines (Inactivated). Management: The effectiveness of vaccines may be decreased. All age-appropriate vaccines must be completed at least two weeks before you start an immunosuppressant. Re-vaccinate anyone who was vaccinated while on immunosuppressant therapy.
Vemurafenib	High risk of Inhibitors causing an increase in serum CYP1A2 substrates. Management: If the CYP1A2 substrat has a narrow therapeutic index, consider alternatives. Separate drug interaction monographs are available for drugs that have been excluded from this monograph.
Risk Factor X (Avoid Combination)
BCG (Intravesical).	The therapeutic effects of BCG (Intravesical) may be diminished by immunosuppressants
BCG (Intravesical).	Myelosuppressive agents may reduce the therapeutic effects of BCG (Intravesical).
Cladribine	May increase the immunosuppressive effects of Immunosuppressants.
Cladribine	May increase the myelosuppressive effects of myelosuppressive agents.
Deferiprone	Deferiprone may have a neutropenic effect that myelosuppressive agents can increase.
Denosumab	Might increase the toxic/adverse effects of Immunosuppressants. In particular, there may be an increase in the risk of serious infections.
Dipyrone	May increase the toxic/adverse effects of Myelosuppressive Agents. In particular, there may be an increase in the risk of pancytopenia and agranulocytosis.
Natalizumab	Natalizumab's toxic/adverse effects may be exacerbated by immunosuppressants. Particularly, concurrent infections may increase.
Pimecrolimus	May increase the toxic/adverse effects of Immunosuppressants
Tacrolimus - Topical	May increase the toxic/adverse effects of Immunosuppressants
Vaccines (Live).	Immunosuppressants can increase the toxic/adverse effects of Vaccines (Live). Immunosuppressants can decrease the therapeutic effects of Vaccines. Management: Live-attenuated vaccines should be avoided for at least three months following immunosuppressants.

Monitoring parameters:

CBC with Differential:

This is a blood test that checks the different types of cells in your blood.
It can tell if you have an infection, inflammation, or other conditions.

Liver Function:

These tests check how well your liver is working.
They can tell if there's liver damage or inflammation.
It's important to monitor liver function when taking certain medications, like dacarbazine.

How to administer Dacarbazine?

Nausea and Vomiting:

Dacarbazine can make people feel very sick.
Doctors recommend taking medicines to prevent nausea and vomiting.

How to Give the Drug (IV Infusion):

It should be given slowly, over 15 to 60 minutes.
If given too quickly, it can irritate the veins.
Different treatments might have different timings; always check specific instructions.

Irritation and Local Reactions:

Dacarbazine can irritate the skin.
Watch the area where the drug is given for any signs of a reaction.

Mechanism of action of Dacarbazine:

Dacarbazine is a medicine that changes inside the body to become an active form called MTIC.
This happens with the help of a system in our body called cytochrome P450.
MTIC damages the DNA of cells, causing them to break and die.
This medicine doesn't target a specific part of the cell's life cycle, so it can act at any time (Marchesi 2007).

Distribution:

It spreads more than just in the body's water.
It likely attaches to some parts of the body, probably the liver (Perry 2012).

Changing Form (Metabolism):

The liver changes dacarbazine into its active form called MTIC.

How Long It Stays (Half-life):

Initially: 19 minutes, but can be 55 minutes if there are liver or kidney issues.
Finally: 5 hours, but can be 7.2 hours with liver or kidney problems.

Leaving the Body (Excretion):