Dacarbazine

Approved Indications:

• Malignant Melanoma: Treatment of metastatic malignant melanoma as part of combination chemotherapy or as monotherapy.
• Hodgkin Lymphoma: Used in combination chemotherapy regimens (e.g., ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine) for classical Hodgkin lymphoma.
• Soft Tissue Sarcomas: For certain advanced or metastatic soft tissue sarcomas.
• Neuroendocrine Tumors: Occasionally used in treatment protocols.

Clinically Accepted Off-label Uses:

• Treatment of non-Hodgkin lymphoma in select cases.
• Palliative chemotherapy in some other advanced solid tumors.
• Investigational uses in various other cancers under clinical trial settings.

Adults:

• Malignant Melanoma (Monotherapy):
• 250 mg/m² intravenous (IV) infusion over 60 minutes, daily for 5 consecutive days every 28 days.
• Hodgkin Lymphoma (ABVD Regimen):
• 375 mg/m² IV on days 15 and 22 of each 28-day cycle.
• Soft Tissue Sarcomas:
• Dose varies; commonly 200–250 mg/m² IV every 3 weeks or as per protocol.

Pediatrics:

• Safety and efficacy not well established; dosing individualized based on body surface area and specific protocols.

Elderly:

• No specific dose adjustment recommended but monitor for toxicity due to reduced organ function.

Renal Impairment:

• Use with caution; no formal dose adjustment guidelines but monitor renal function and toxicity.

Hepatic Impairment:

• No specific dose adjustments; caution advised.

Route of Administration:

• Intravenous infusion over 60 minutes.
• Must be administered in a healthcare setting with monitoring.

Dacarbazine is an alkylating agent and a prodrug that requires metabolic activation in the liver to its active form, monomethyl triazeno imidazole carboxamide (MTIC). MTIC methylates DNA at the O6 and N7 positions of guanine residues, causing DNA strand breaks and inhibition of DNA, RNA, and protein synthesis. This cytotoxic effect triggers apoptosis in rapidly dividing cancer cells, leading to antitumor activity in melanoma, lymphoma, and other malignancies.

Absorption:

• Not applicable (IV administration).

Distribution:

• Widely distributed throughout the body, including tumor tissue.

Metabolism:

• Metabolized hepatically via microsomal enzymes to active metabolite MTIC.

Elimination:

• Excreted primarily in urine.

Half-life:

• Approximately 40–60 minutes.

Onset of Action:

• Cytotoxic effects accumulate over treatment cycles.

• Pregnancy:
• FDA Category D: Positive evidence of human fetal risk. Use only if benefits outweigh risks.
• Teratogenic and embryotoxic effects observed; contraindicated during pregnancy unless absolutely necessary.
• Lactation:
• Unknown if excreted in human milk.
• Avoid breastfeeding during treatment due to potential toxicity.
• Caution:
• Women of childbearing potential should use effective contraception during and after treatment.

• Primary Class: Antineoplastic Agent
• Subclass: Alkylating Agent (Triazene derivative)

• Hypersensitivity to dacarbazine or any components of the formulation.
• Severe bone marrow suppression.
• Active infection or severe immunosuppression.
• Pregnancy unless benefits clearly outweigh risks.

• Myelosuppression: Monitor blood counts regularly; risk of neutropenia, thrombocytopenia, and anemia.
• Hepatotoxicity: Monitor liver function tests during treatment.
• Renal Function: Monitor renal function; dose adjustments may be needed based on toxicity.
• Secondary Malignancies: Long-term risk of secondary leukemia with alkylating agents.
• Infusion Reactions: Monitor for allergic reactions during infusion.
• Photosensitivity: Patients may be more sensitive to sunlight; advise protection.

Common:

• Hematologic: Leukopenia, thrombocytopenia, anemia.
• Gastrointestinal: Nausea, vomiting (often severe), anorexia, diarrhea.
• Constitutional: Fatigue, fever, malaise.
• Dermatologic: Rash, photosensitivity.

Serious:

• Severe myelosuppression leading to infection or bleeding.
• Hepatotoxicity.
• Allergic reactions/anaphylaxis (rare).
• Secondary malignancies (long-term).

• Other Myelosuppressive Agents: Additive bone marrow toxicity.
• Live Vaccines: Contraindicated during therapy.
• Hepatotoxic Drugs: Use caution due to potential additive liver toxicity.
• Enzyme Inducers/Inhibitors: May alter metabolism, though clinical significance uncertain.

• Continued role as part of first-line regimens in Hodgkin lymphoma.
• Emerging data on combination therapies in melanoma and sarcomas.
• Updated antiemetic guidelines emphasize aggressive prophylaxis due to high nausea risk.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Use reconstituted solution immediately or store refrigerated (2°C to 8°C) and discard after 24 hours.
• Handle with care; cytotoxic precautions required.