Advanced Breast Cancer: Learn about treatment options.

Dacarbazine

Pronunciation: da-CAR-buh-zeen
Class: Alkylating agent, Triazine

Trade Names

DTIC-Dome
- Powder for injection 100 mg
- Powder for injection 200 mg

Pharmacology

Exact mechanism is unknown. Three mechanisms are hypothesized: 1) inhibition of DNA synthesis by acting as a purine analog; 2) action as an alkylating agent; and 3) interaction with sulfhydryl groups.

Slideshow: Hitting the Beach? Soak Up These Top Sun Safety Tips

Pharmacokinetics

Distribution

Vd exceeds total body water content, suggesting localization in some body tissue, probably liver. Not appreciably bound to proteins.

Metabolism

Extensive major metabolite is 5-amino-imidazole-4 carboxamide.

Elimination

Biphasic, initial t ½ is 19 min and terminal t ½ is 5 h; 40% excreted unchanged in urine in 6 h.

Special Populations

Hepatic Function Impairment

Initial t ½ increased to 55 min and terminal t ½ increased to 7.2 h in a patient with renal and hepatic function impairment.

Indications and Usage

Treatment of metastatic malignant melanoma; in combination with other agents as second-line therapy for Hodgkin disease.

Unlabeled Uses

In combination with cyclophosphamide and vincristine for malignant pheochromocytoma; in combination with other agents for treatment of advanced metastatic soft tissue sarcoma; alone or in combination with other agents for management of Kaposi sarcoma.

Contraindications

Standard considerations.

Dosage and Administration

Malignant Melanoma
Adults

IV 2 to 4.5 mg/kg/day for 10 days is recommended; may be repeated at 4 wk intervals. Alternatively, administer 250 mg/m 2 daily for 5 days; may be repeated every 3 wk.

Hodgkin Disease
Adults

IV 150 mg/m 2 daily for 5 days in combination with other effective drugs is recommended; may be repeated every 4 wk. Alternatively, 375 mg/m 2 on day 1 in combination with other effective drugs, repeated every 15 days.

General Advice

  • Follow institutional and NIH procedures for handling, administration, and disposal of anticancer drugs.
  • Reconstitute 100 mg vial with 9.9 mL sterile water for injection. Reconstitute 200 mg vial with 19.7 mL sterile water for injection. Resulting solution contains 10 mg/mL of dacarbazine.
  • Reconstituted solution may be further diluted with dextrose 5% injection or sodium chloride injection for administration as an IV infusion.
  • To reduce GI adverse reactions, restrict the patient's food intake for 4 to 6 h prior to treatment if possible.

Storage/Stability

Store unopened vials in refrigerator (36° to 46°F). Protect from light. Store reconstituted solution in vial at 39.2°F for up to 72 h or at normal room conditions for up to 8 h. If reconstituted solution is further diluted with dextrose 5% injection or sodium chloride injection, store diluted solution at 39.3°F for up to 24 h or at normal room conditions for up to 8 h.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Dermatologic

Alopecia; facial flushing; erythematous and urticarial rashes.

GI

Anorexia, nausea, vomiting (over 90% with initial few doses).

Hematologic

Bone marrow suppression.

Lab Tests

Abnormal liver or renal function tests.

Musculoskeletal

Myalgia.

Miscellaneous

Flu-like syndrome; malaise; facial paresthesia.

Precautions

Warnings

Administer under supervision of a qualified physician experienced in use of cancer chemotherapeutic agents; hemopoietic depression is most common toxicity; hepatic necrosis has been reported; carcinogenic and teratogenic effects demonstrated in animals; weigh possibility of achieving therapeutic benefit against risk of toxicity when treating patient.


Monitor

Ensure that CBC with differential and platelet count is evaluated before starting therapy and then frequently during therapy. Implement infection control measures if WBC drops; implement bleeding precautions if platelet count drops. Assess injection site frequently for signs or symptoms of extravasation (eg, burning, pain, induration). Monitor patient for signs and symptoms of bacterial, viral, or fungal infection.


Pregnancy

Category C .

Lactation

Undetermined.

Hemopoietic depression

Hemopoietic depression is the most common toxicity and involves primarily leukocytes and platelets, although anemia sometimes occurs. Leukopenia and thrombocytopenia may be severe enough to cause death. Possible bone marrow suppression requires careful monitoring of RBC, WBC, and platelets.

Hepatotoxicity

Hepatotoxicity, accompanied by hepatic vein thrombosis and hepatocellular necrosis resulting in death, may occur.

Vomiting

Consider using phenobarbital and/or prochlorperazine for recurrent or prolonged vomiting.

Overdosage

Symptoms

Bone marrow suppression.

Patient Information

  • Advise patient, family, or caregiver that medication will be prepared and administered by health care providers in a health care setting.
  • Advise patient, family, or caregiver that medication may be used in combination with other agents, including antiemetics and sedatives, to achieve max benefit possible.
  • Advise patient, family, or caregiver that restricting food intake for 4 to 6 h before treatment may help reduce nausea and vomiting.
  • Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing; fever, chills, or other signs of infection; unusual bleeding or bruising; pain, redness, or swelling at injection site.
  • Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness.
  • Advise patient, family, or caregiver that hair loss is a common adverse reaction of therapy, but that this is usually reversible after therapy has been completed.
  • Caution women of childbearing potential to avoid becoming pregnant during therapy.

Copyright © 2009 Wolters Kluwer Health.

Advanced Breast Cancer: Learn about treatments to improve quality of life. Click Here

Close
Hide
(web2)