High dose Chemotherapy

Dactinomycin Administartion

"The VAC combination was used extensively in previous IRS studies (I, II, and III) and VOD was not reported during these studies, strongly suggesting that the escalation of the cyclophosphamide dose to 2.2 g/m2 (with the vincristine and actinomycin D doses and schedule remaining unchanged) triggered the development of VOD."             Ortega     et al. 1997

Some Doctors continue pushing the limits of dosing in drugs for children. This unethical conduct only results in higher toxic adverse reactions, and deaths. Below is an example of the limits that were pushed with Daniella.

Dactinomycin (Cosmegen) - Daniella's doses in the study are listed below this article.

Dosage And Administration: Toxic reactions due to dactinomycin are frequent and may be severe (see Adverse Effects), thus limiting in many instances the amount that may be given. However, the severity of toxicity varies markedly and is only partly dependent on the dose employed. The drug must be given in short courses.

I.V.: The dosage of dactinomycin varies depending on the tolerance of the patient, the size and location of the neoplasm, and the use of other forms of therapy. It may be necessary to decrease the usual dosages suggested below when other chemotherapy or x-ray therapy is used concomitantly or has been used previously.

The dosage for adults or children should not exceed 15 µg/kg or 400 to 600 µg/mof body surface daily i.v. for 5 days. Calculation of the dosage for obese or edematous patients should be on the basis of surface area in an effort to relate dosage to lean body mass.

Adults: The usual adult dosage is 500 µg (0.5 mg) daily i.v. for a maximum of 5 days.

Children: In children 15 µg (0.015 mg)/kg of body weight is given i.v. daily for 5 days. An alternative schedule is a total dosage of 2 500 µg (2.5 mg)/mof body surface given i.v. over a 1-week period.

In both adults and children, a second course may be given after at least 3 weeks have elapsed, provided all signs of toxicity have disappeared.

Reconstitute dactinomycin by adding 1.1 mL of Sterile Water for Injection (without preservative) using aseptic precautions. The resulting solution of dactinomycin will contain approximately 500 µg or 0.5 mg/mL.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. When reconstituted, dactinomycin is a clear, gold-colored solution.

Once reconstituted, the solution of dactinomycin can be added to infusion solutions of Dextrose Injection 5% or Sodium Chloride Injection either directly or to the tubing of a running i.v. infusion.

Although reconstituted dactinomycin is chemically stable, the product does not contain a preservative and accidental microbial contamination might result. Any unused portion should be discarded. Use of water containing preservatives (benzyl alcohol or parabens) to reconstitute dactinomycin for injection, results in the formation of a precipitate.

Partial removal of dactinomycin from i.v. solutions by cellulose ester membrane filters used in some i.v. in-line filters has been reported.

Since dactinomycin is extremely corrosive to soft tissue, precautions for materials of this nature should be observed.

If the drug is given directly into the vein without the use of an infusion, the two-needle technique should be used. Reconstitute and withdraw the calculated dose from the vial with one sterile needle. Use another sterile needle for direct injection into the vein.

Discard any unused portion of the dactinomycin solution.

Isolation-Perfusion Technique: The dosage schedules and the technique itself vary from one investigator to another; the published literature, therefore, should be consulted for details. In general, the following doses are suggested: 50 µg (0.05 mg)/kg of body weight for lower extremity or pelvis. 35 µg (0.035 mg)/kg of body weight for upper extremity.

It may be advisable to use lower doses in obese patients, or when previous chemotherapy or radiation therapy has been employed.

Complications of the perfusion technique are related mainly to the amount of drug that escapes into the systemic circulation and may consist of hemopoietic depression, absorption of toxic products from massive destruction of neoplastic tissue, increased susceptibility to infection, impaired wound healing, and superficial ulceration of the gastric mucosa. Other side effects may include edema of the extremity involved, damage to soft tissues of the perfused area, and (potentially) venous thrombosis.

Special Handling: Due to the drug's toxic and mutagenic properties, appropriate precautions including the use of appropriate safety equipment are recommended for the preparation of dactinomycin for parenteral administration. The National Institutes of Health presently recommend that the preparation of injectable antineoplastic drugs should be performed in a Class II laminar flow biological safety cabinet and that personnel preparing drugs of this class should wear surgical gloves and a closed front surgical-type gown with knit cuffs.

Availability And Storage: Each vial contains: lyophilized, amorphous yellow dactinomycin powder 500 µg and mannitol 20 mg. Forms a clear gold-colored solution on reconstitution. Protect from light.

St. Louis Children's Hospital Doses

Daniella's dose was 1.5/m2 x BSA (.57 & .50) =  0.85 and 0.75 mg

Doses recomended from industry standards and Merck & CO., Inc

Regular dose recommendations for Daniella ranged from 0.18mg, to highest Merck Recommendations from package insert =  0.34 mg.
Any deviation from these regimins can cause toxic reactions.

Links about Cosmegen.

• CancerCare Web Site (pdf file)
• Merck Package Insert (pdf file)
• CTCLConsult Web Site
• BC Cancer Agency

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