Dactinomycin Anticancer Drug

INTRODUCTION

Dactinomycin, also known as actinomycin D, is the most significant member of actinomycines, which are a class of polypeptide antitumor antibiotics isolated from soil bacteria of the genus Streptomyces.[1] It is one of the older anticancer drugs, and has been used for many years.

THERAPEUTIC USES:

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

• Gestational trophoblastic neoplasia

• Wilms' tumor

• Rhabdomyosarcoma

• Ewing's sarcoma

• Malignant hydatidiform mole

Sometimes it will be combined with other drugs in chemotherapy regimens, like the VAC regimen (with vincristine and cyclophosphamide) for treating rhabdomyosarcoma and Ewing's sarcoma.

It is also used as a radiosensitizer in adjunct to radiotherapies, since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation

ADVERSE EFFECT:

• Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue);

• black, tarry, or bloody stools; chest pain; diarrhea; fever, chills, or sore throat; flushing; leg pain or swelling; muscle pain or aches; red, swollen, blistering, or peeling skin; redness, swelling, pain, or blistering near the injection site;

• severe or persistent nausea or vomiting; shortness of breath; swelling, sores, or ulcers of the mouth, tongue, or lips; symptoms of liver problems (eg, dark urine, pale stools, persistent loss of appetite, severe stomach pain,

 yellowing of the skin or eyes); trouble swallowing; unusual bruising or bleeding; unusual tiredness or weakness.

MECHANISM OF ACTION:

In cell biology, actinomycin D is shown to have the ability to inhibit transcription. Actinomycin D does this by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase

PHARMACOKINETICS:

Pharmacokinetic data analysis suggested that a three-compartment model most accurately reflected dactinomycin pharmacokinetics. However, there was insufficient data available to fully characterize this model. A median peak plasma concentration (Cmax) of 25.1 mg/ml (range, 3.2-99.2 mg/ml) was observed at 15 minutes after administration. The median exposure (AUC0-6), determined in 16 patients with sampling to 6 hours, was 2.67 mg/L.min (range, 1.12-4.90 mg/L.min). After adjusting for body size, AUC0-6 and Cmax were positively related to dose (P = 0.03 and P = 0.04, respectively). Patients who experienced any level of Common Toxicity Criteria grade had a 1.46-fold higher AUC0-6, 95% confidence interval (1.02-2.09). AUC0-6 was higher in patients <40 kg, possibly indicating a greater toxicity risk.

PRECAUTIONS: 

Dactinomycin is very toxic. Do not inhale the dust or vapors of dactinomycin. Do not get dactinomycin in your eyes, nose, or mouth, or onto your skin. Do not come into contact with dactinomycin if you are pregnant. Dactinomycin is given through a vein. If dactinomycin leaks out of the vein (extravasation), severe damage to the area around the injection site will occur. Tell your doctor or health care provider immediately if you notice any discomfort, pain, or redness at the injection site.

• if you are pregnant, planning to become pregnant, or are breast-feeding

• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

• if you have allergies to medicines, foods, or other substances

• if you have bone marrow problems or an infection, are scheduled to receive a vaccine, or are very overweight

• if you are scheduled to have radiation therapy, have had radiation therapy in the last several months, or are receiving any other cancer therapy

DRUG-DRUG INTERACTIONS:

• Drug + kidney patient  = may result in renal failure

• Drug + antibiotics= synergistic effect may increase side effect

• Drug + antiemetic = synergistic effect may cause weakness and nausea.

REFERENCE: Tripathi K.D; "Essentials of medical pharmacology"; Page no-858,859,867