Dacarbazine

Indications

Dacarbazine is used for: Metastatic melanoma, Hodgkin's disease, Soft tissue sarcoma

Adult Dose

Intravenous Metastatic melanoma Adult: 2-4.5 mg/kg daily for 10 days, repeat at 4-wk intervals or 200-250 mg/m2 BSA daily for 5 days, repeat at 3-wk intervals or 850 mg/m2 BSA by infusion, repeat at 3-wk intervals. Hodgkin's disease Adult: 150 mg/m2 BSA daily for 5 days, repeat every 4 wk or 375 mg/m2 BSA every 15 days in combination with other agents. Soft tissue sarcoma Adult: 250 mg/m2 BSA daily for 5 days repeated every 3 wk. Usually given with doxorubicin.

Child Dose

Hodgkin's Disease With other antineoplastics, eg ABVD Dosage dependent on protocol150 mg/m² IV qDay for 5 days, repeat q4Weeks OR 375 mg/m² IV on Day 1; repeat every 15 Days

Renal Dose

Renal Impairment CrCl 46-60 mL/min: 80% of regular dose CrCl 31-45 mL/min: 75% of regular dose CrCl <30 mL/min: 70% of regular dose

Administration

IV Preparation Reconstitute with a 9.9 mL (100 mg vial) or 19.7 mL (200 mg vial) of SWI to obtain a 10 mg/mL soln For infusion, dilute with D5W or NS up to 250 mL IV Administration IVP over 1 min (may be irritant & painful) OR infusion over 15-60 min

Contra Indications

Bone marrow suppression Hypersensitivity Breastfeeding Severe anemia, severe thrombocytopenia

Precautions

The drug should be administered under the supervision of an experienced cancer chemotherapy physician. The most common toxicity for injectable dacarbazine is hemopoietic (bone marrow) depression Hepatic necrosis reported Carcinogenic and teratogenic effects reported in animals. The physician must weigh the possible therapeutic benefits against the risks of toxicity. May cause severe pain & burning at injection site & along vein; to alleviate, may increase diluent, reduce infusion rate & apply cold compresses Risk of potentially fatal hepatocellular necrosis Avoid pregnancy Monitor: CBC, LFTs

Pregnancy-Lactation

Pregnancy Category: C Lactation: not known if excreted in breast milk, do not nurse

Interactions

Impairs immune response to vaccines; possible infection after admin of live vaccines. Effect increased by CYP1A2 inhibitors e.g. amiodarone, ciprofloxacin, fluvoxamine, ketoconazole, lomefloxacin, ofloxacin and rofecoxib. Effect decreased by CYP1A2 inducers e.g. aminoglutethimide, carbamazepine, phenobarbital and rifampicin. Contraindicated (0) Serious (14) adenovirus types 4 and 7 live, oral axicabtagene ciloleucel brexucabtagene autoleucel ciltacabtagene autoleucel etrasimod givosiran idecabtagene vicleucel influenza virus vaccine quadrivalent, adjuvanted influenza virus vaccine trivalent, adjuvanted lisocabtagene maraleucel palifermin ropeginterferon alfa 2b tisagenlecleucel tofacitinib

Adverse Effects

Side effects of Dacarbazine : >10% Nausea (>90%),Vomiting(>90%),Injection site pain,Leukopenia,Thrombocytopenia 1-10% Alopecia,Rash,Photosensitivity,Anorexia,Metallic taste,Flu-like syndrome Frequency Not Defined Anaphylaxis,Photosensitivity (rare),Cerebral hemorrhage,Seizure,Myelosuppression,Hepatic necrosis,Hepatic vein thrombosis,Hepatotoxicity Potentially Fatal: Myelosuppression; hepatotoxicity, anaphylaxis.

Mechanism of Action

The exact mechanism of action is still unclear but it appears to form methylcarbonium ions that attack nucleophilic groups by attaching to the 7-position of guanine on DNA. It also cross-links DNA strands leading to inhibition of DNA, RNA and protein synthesis.