Dictionary:

dactinomycin

  (dăk'tə-nō-mī'sĭn)

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An antibiotic of the actinomycin group, C₆₂H₈₆N₁₂O₁₆, isolated from bacteria and used as an antineoplastic agent in the treatment of certain cancers. Also called actinomycin D.

[D– + ACTINOMYCIN.]

Key Terms: Antineoplastics, Cytotoxic, Ewing's sarcoma, Gestational trophoblastic cancer, Kaposi's sarcoma, Myeloma, Oncologist, Rhabdomyosarcoma.

Definition

Dactinomycin is a chemotherapeutic agent belonging to a family of medicines known as antineoplastic drugs. Alternative trade names or brand names for dactinomycin include Actinomycin-D and Cosmegen.

Description

Dactinomycin is one of the older chemotherapy drugs, having gained approval from the Food and Drug Administration (FDA) in 1982. This highly potent and effective cytotoxic agent is a mixture of substances produced by the bacteria Streptomyces parvullus. Its toxic properties prevent its use as an antibiotic.

Dactinomycin interferes with the growth of cancer cells by complexing with a cell's genetic material (deoxyribonucleic acid, or DNA). This prevents the cell from producing the proteins necessary to function and grow, thereby killing it. Dactinomycin may be used as a single chemotherapeutic agent or in conjunction with other antineoplastics (such as vincristine and cyclophosphamide) for greater efficacy.

Purpose

Dactinomycin is used in the treatment of Ewing's sarcoma, Wilms' tumor, rhabdomyosarcoma, gestational trophoblastic tumors, Kaposi's sarcoma, and soft tissue sarcomas. It is less commonly used for cancers of the uterus and testis.

Recommended Dosage

The exact schedule and method of dactinomycin administration will be prescribed by an oncologist based on the type and stage of the cancer. An appropriate starting treatment regimen for adult patients is 500 mg/day for five consecutive days at two to four week intervals if the drug is tolerated. For children the dose is 15 mg/day over the same time course as prescribed for adults. Dactinomycin is not recommended for children less than one year of age; little clinical data is available on the use of dactinomycin in the elderly. Administration may be by intravenous (IV) injection, through a running IV infusion, or through a central line inserted under the skin into a vein near the collarbone.

Precautions

To maximize treatment effects, patients receiving dactinomycin should observe the following guidelines, as well as any modifications given by the oncologist:

• The area surrounding the injection site should be monitored.
• Patients should have regular laboratory testing for white blood cell count and kidney, liver, and bone marrow function.
• In order to reduce the possibility of immunosuppression, immunizations not approved or prescribed by the oncologist should be avoided.
• Patients should avoid contact with individuals taking or that have recently taken the oral polio vaccine, or individuals that have an active infection. When necessary a protective facemask should be worn.
• Oral hygiene procedures should be followed to reduce the risk of gum abrasion.
• Patients should not touch eye and nasal areas unless hands have been properly washed immediately prior to contact.
• To reduce bleeding and bruising complications, patients should exercise extreme caution when handling sharp instruments and decline participation in contact sports.
• Prior to treatment, the patient's medical history should be thoroughly reviewed to avoid complications that might arise from previous conditions such as gout, kidney stones, liver disease, chickenpox, shingles, or a history of allergic reactions to various drugs.
• The oncologist should be made aware if the patient is pregnant or if there is the possibility the patient might be pregnant, or if the patient is a breast-feeding mother.
• Only prescribed medications or over the counter (OTC) drugs approved by the oncologist should be taken by a patient receiving dactinomycin.

Side Effects

Possible side effects of treatment with dactinomycin should be discussed with the patient prior to initiation of treatment. The patient should be instructed to notify the oncologist of any side effects. Side effects that may not be life threatening but give the patient cause for concern include hair loss (alopecia), intermittent diarrhea, nausea and vomiting, loss of appetite, difficulty swallowing, mouth sores or ulcers, and a general rash or change in skin tone. Side effects that should be reported immediately to the oncologist include unusual bleeding or bruising, black tarry stools, blood in the urine or stool, development of a cough, wheezing or hoarseness, fever or chills, lower back or side pain, painful or difficult urination, pinpoint red spots on the skin, and pain at the site of the injection. The oncologist will decide what type of intervention is best suited to control or extinguish the presented side effects, including changing the dosage, changing the treatment schedule, or discontinuing dactinomycin treatment.

Interactions

Certain medications should never be used together, but there are cases in which multiple drug treatment may be advisable even when drug interaction is well documented. Dactinomycin may be used in conjunction with other antineoplastic drugs or radiation therapy for increased efficacy of treatment. Under such conditions the oncologist will balance dosage and treatment schedules to maximize the positive effects of all drugs given and minimize any negative interactions.

It is essential that the oncologist be aware of any drugs that the patient is presently taking or has recently taken, or if the patient has recently received radiation therapy. A careful review of drugs that may interact with dactinomycin to lower its efficiency should be covered with the patient prior to treatment. These may include, but are not limited to, amphotericin B, antithyroid agents, azathioprine, chloramphenicol, flucytosine, ganciclovir, interferon, plicamycin, zidovudine, probenecid, and sulfinpyrazone.

—Jane Taylor-Jones, Research Associate, M.S.

An antibiotic isolated from bacteria and used as an antineoplastic agent in the treatment of certain cancers.

An antibiotic of the actinomycin complex (actinomycin D), produced by several species of Streptomyces; used as an antineoplastic agent.

Actinomycin
Systematic (IUPAC) name
(Dactinomycin )
Identifiers
CAS number	50-76-0
ATC code	L01DA01
PubChem	2019
DrugBank	APRD00124
Chemical data
Formula	C62H86N12O16
Mol. mass	1255.42 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	5%
Metabolism	?
Half life	36 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Actinomycin is any of a class of polypeptide antibiotics isolated from soil bacteria of the genus Streptomyces.

Mechanism

Actinomycin-D is primarily used as an investigative tool in cell biology to inhibit transcription. It does this by binding DNA at the transcription initiation complex and preventing elongation by RNA polymerase.^[1]

As it can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis.

Clinical use

As chemotherapy

Actinomycin-D is marketed under the trade name Dactinomycin. Actinomycin-D is one of the older chemotherapy drugs which has been used in therapy for many years.

It is a clear, yellow liquid which is administered intravenously and most commonly used in treatment of a variety of cancers, including:

• gestational trophoblastic neoplasia^[2]
• Wilms' tumor^[3]
• rhabdomyosarcoma ^[4]

As an antibiotic

It was the first antibiotic shown to have anti-cancer activity, but is not normally used as such, as it is highly toxic, causing damage to genetic material.

It was the first antibiotic ever isolated by Selman Waksman.

Research use

Actinomycin-D and its fluorescent derivative, 7-amino-actinomycin D, are used as stains in microscopy and flow cytometry applications. The affinity of these stains compounds for GC-rich regions of DNA strands makes them excellent markers for DNA.

7-amino-actinomycin D (7aad) is used as a DNA stain .7aad binds to single stranded DNA. Therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones. (Source)

References

1. ^ Sobell H (1985). "Actinomycin and DNA transcription". Proc Natl Acad Sci U S A 82 (16): 5328-31. PMID 2410919. 
2. ^ Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose M. "Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia". Int J Gynecol Cancer 16 (3): 1432-8. PMID 16803542. 
3. ^ Abd El-Aal H, Habib E, Mishrif M (2005). "Wilms' Tumor: The Experience of the Pediatric Unit of Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK)". J Egypt Natl Canc Inst 17 (4): 308-11. PMID 17102824. 
4. ^ Khatua S, Nair C, Ghosh K (2004). "Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues". J Pediatr Hematol Oncol 26 (11): 777-9. PMID 15543019. 

External links

• MedlinePlus DrugInfo medmaster-a682224

Chemotherapeutic agents/Antineoplastic agents (L01)
Alkylating agents	Nitrogen mustards: (Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan). Nitrosoureas:(Carmustine, Fotemustine, Lomustine, Streptozocin). Platinum: (Carboplatin, Cisplatin, Oxaliplatin, BBR3464). Busulfan, Dacarbazine, Procarbazine, Temozolomide, ThioTEPA, Uramustine
Antimetabolites	Folic acid: (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed). Purine:(Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine). Pyrimidine:(Capecitabine, Cytarabine, Fluorouracil, Floxuridine, Gemcitabine)
Spindle poison/mitotic inhibitor	Taxane: (Docetaxel, Paclitaxel). Vinca: (Vinblastine, Vincristine, Vindesine, Vinorelbine).
Cytotoxic/antitumor antibiotics	Anthracycline family: (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Valrubicin) - streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) - Hydroxyurea
Topoisomerase inhibitors	Camptotheca: (Camptothecin, Topotecan, Irinotecan), Podophyllum:(Etoposide, Teniposide)
CI monoclonal antibodies	Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Panitumumab, Rituximab, Tositumomab, Trastuzumab
Photosensitizers	Aminolevulinic acid, Methyl aminolevulinate, Porfimer sodium, Verteporfin
Tyrosine kinase inhibitors	Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Nilotinib, Sorafenib, Sunitinib
Other	retinoids (Alitretinoin, Tretinoin) - Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase (Pegaspargase), Bexarotene, Bortezomib, Denileukin diftitox, Estramustine, Masoprocol, Mitotane

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