No

Antineoplastic Agent, Antibiotic

Treatment of testicular tumors, melanoma, choriocarcinoma, Wilms' tumor, neuroblastoma, retinoblastoma, rhabdomyosarcoma, uterine sarcomas, Ewing's sarcoma, Kaposi's sarcoma, and soft tissue sarcoma

C

Hypersensitivity to dactinomycin or any component; patients with chickenpox or herpes zoster; avoid in infants <6 months of age

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Drug is extremely irritating to tissues and must be administered I.V.; if extravasation occurs during I.V. use, severe damage to soft tissues will occur; use with caution in patients who have received radiation therapy or in the presence of hepatobiliary dysfunction; reduce dosage in patients who are receiving radiation therapy simultaneously.

>10%:

Central nervous system: Unusual fatigue, malaise, fever

Dermatologic: Alopecia (reversible), skin eruptions, acne, increased pigmentation of previously irradiated skin

Extravasation: An irritant and should be administered through a rapidly running I.V. line; extravasation can lead to tissue necrosis, pain, and ulceration

Vesicant chemotherapy

Endocrine & metabolic: Hypocalcemia

Gastrointestinal: Highly emetogenic

Severe nausea and vomiting occurs in most patients and persists for up to 24 hours; stomatitis, anorexia, abdominal pain, esophagitis, diarrhea

Time course of nausea/vomiting: Onset: 2-5 hours; Duration: 4-24 hours

Hematologic: Myelosuppressive: Dose-limiting toxicity; anemia, aplastic anemia, agranulocytosis, pancytopenia

WBC: Moderate

Platelets: Moderate

Onset (days): 7

Nadir (days): 14-21

Recovery (days): 21-28

1% to 10%: Gastrointestinal: Diarrhea, mucositis

<1%: Hyperuricemia, hepatitis, LFT abnormalities, anaphylactoid reaction

Symptoms of overdose include myelosuppression, nausea, vomiting, glossitis, oral ulceration

There are no known antidotes and treatment is primarily symptomatic and supportive

Increased toxicity: Dactinomycin potentiates the effects of radiation therapy: Radiation may cause skin erythema which may become severe and is also associated with incidence of GI toxicity

Store intact vials at room temperature (30°C) and protect from light; storage at high temperatures (up to 50°C) for up to 2 weeks is permissible

Dilute with 1.1 mL of preservative-free SWI to yield a final concentration of 500 mcg/mL; do not use preservative diluent as precipitation may occur. Solution is chemically stable for 24 hours at room temperature (25°C). Significant binding of the drug occurs with micrometer nitrocellulose filter materials.

Compatible with D₅W or NS

Standard I.V. dilution:

I.V. push: Dose/syringe (500 mcg/mL)

IVPB: Dose/50 mL D₅W or NS

Stable for 24 hours at room temperature

Binds to the guanine portion of DNA intercalating between guanine and cytosine base pairs inhibiting DNA and RNA synthesis and protein synthesis; product of Streptomyces parvullus (a yeast species)

Distribution: Poor penetration into CSF; crosses placenta; high concentrations found in bone marrow and tumor cells, submaxillary gland, liver, and kidney

Metabolism: Minimal

Half-life: 36 hours

Time to peak serum concentration: I.V.: Within 2-5 minutes

Elimination: ~10% of dose excreted as unchanged drug in the urine, 14% excreted in feces, while 50% appears in the bile

Refer to individual protocols

Children >6 months and Adults: I.V.:

15 mcg/kg/day or 400-600 mcg/m²/day (maximum: 500 mcg) for 5 days, may repeat every 3-6 weeks or

2.5 mg/m² given in divided doses over 1-week period and repeated at 2-week intervals or

0.75-2 mg/m² as a single dose given at intervals of 1-4 weeks have been used

Dosing in renal impairment: No adjustment necessary

CBC with differential and platelet count, liver function tests, and renal function tests

Sedation is common

May cause myelosuppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Limit oral intake for 4-6 hours before therapy. Do not use alcohol, aspirin-containing products and OTC medications without consulting prescriber. It is important to maintain adequate nutrition and hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) during therapy; frequent small meals may help. You may experience nausea or vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help). If this is ineffective consult prescriber for antiemetic medication. You may experience loss of hair (reversible); you will be more susceptible to infection (avoid crowds and exposure to infection as much as possible); you will be more sensitive to sunlight; use sunblock, wear protective clothing and dark glasses, or avoid direct exposure to sunlight. Flu-like symptoms (eg, malaise, fever, myalgia) may occur 1 week after infusion and persist for 1-3 weeks; consult prescriber for severe symptoms. Report fever, chills, unusual bruising or bleeding, signs of infection, excessive fatigue, yellowing of eyes or skin, or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Care should be taken to avoid extravasation of the drug; an in-line cellulose membrane filter should not be used during administration of dactinomycin solutions; do not administer I.M. or S.C.

Powder for injection, lyophilized: 0.5 mg

Berg SL, Grisell DL, DeLaney TF, et al, "Principles of Treatment of Pediatric Solid Tumors," Pediatr Clin North Am, 1991, 38(2):249-67.

Berkowitz RS and Goldstein DP, "Gestational Trophoblastic Disease," Cancer, 1995, 76(10 Suppl): 2079-85.

Carli M, Pastore G, Perilongo G, et al, "Tumor Response and Toxicity After Single High-Dose Versus Standard Five-Day Divided Dose Dactinomycin in Childhood Rhabdomyosarcoma," J Clin Oncol, 1988, 6(4):654-8.

Horowitz ME, "Ewing's Sarcoma: Current Status of Diagnosis and Treatment," Oncology, 1989, 3(3):101-6.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Mehta MP, Bastin KT, and Wiersma SR, "Treatment of Wilms' Tumor. Current Recommendations," Drugs, 1991, 42(5):766-80.