Dactinomycin

Indications

Dactinomycin is used for: Wilms Tumor, Rhabdomyosarcoma, Ewing Sarcoma, Gestational Trophoblastic Neoplasms, Testicular Cancer,

Adult Dose

Intravenous Childhood rhabdomyosarcoma, Ewing's sarcoma, Wilm's tumour Adult: 15 mcg/kg daily for 5 days, in combination regimens. Max: 15 mcg/kg or 400-600 mcg/m2 daily for 5 days per 2-wk cycle. Metastatic nonseminomatous testicular cancer Adult: 1 mg/m2 on day 1 of combination regimens. Max: 15 mcg/kg or 400-600 mcg/m2 daily for 5 days per 2-wk cycle. Gestational trophoblastic tumours Adult: 12 mcg/kg daily for 5 days as a single agent or 500 mcg daily on days 1 and 2 of combination regimens. Max: 15 mcg/kg or 400-600 mcg/m2 daily for 5 days per 2-wk cycle.

Child Dose

Intravenous Childhood rhabdomyosarcoma, Ewing's sarcoma, Wilm's tumour Child: >6 mth Same as adult dose.

Renal Dose

Administration

IV Preparation Follow cytotoxic handling and disposal guidelines Reconstitute with 1.1 mL of preservative-free sterile water for injection to yield a final concentration of 500 mcg/mL Resulting solution should appear clear, gold-colored Further dilute reconstituted product with D5W or 0.9% NaCl to yield concentration >10 mcg/mL Contains no preservative, discard any unused portions IV Administration Vesicant Administer diluted reconstituted product IV over 10-15 minutes Do not use in-line cellulose ester membrane filter Do not give IM or SC

Contra Indications

Hypersensitivity. Patient w/ varicella or herpes zoster infection.

Precautions

Patient w/ impaired bone marrow. Renal and hepatic impairment. Pregnancy and lactation.

Pregnancy-Lactation

Interactions

Combination w/ radiation therapy may result in increased toxicity esp when w/in 2 mth of radiation treatment for right-sided Wilm's tumour. May diminish the therapeutic effect of live vaccines.

Adverse Effects

Side effects of Dactinomycin : Nausea, vomiting, cheilitis, oesophagitis, GI ulceration, proctitis, fever, malaise, hypocalcaemia, myalgia, alopecia, pneumonitis, kidney and liver abnormalities, eruptions, acne, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, severe tissue damage, oedema, neutropenia and febrile neutropenia. Potentially Fatal: Hepatic failure, hepatic veno-occlusive disease, particularly in childn <4 yr, myelosuppression, sepsis, including neutropenic sepsis.

Mechanism of Action

Dactinomycin binds to the guanine portion of DNA forming a complex which interferes w/ DNA and RNA synthesis as well as protein synthesis. It is also immunosuppressive and possesses some hypocalcaemic activity.