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Nursing Pharmacology Chapter 33-34: Anticancer Drugs
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Natural Products:
Topoisomerase Inhibitors Type II: Liposomal Doxorubicin (Pegylated liposomal doxorubicin, Doxil)
Administration of the pegylated form of doxorubicin (liposomal form) results in an extended duration of action as a liposomal form is not subject to appreciable uptake by the reticuloendothelial system.7
Pharmacokinetics of the pegylated form is distinct from the non-liposomal drug preparation.
Liposomal
doxorubicin administration is associated with a reduced side-effect profile
compared to doxorubicin.7
For example, nausea and vomiting occur less frequently with liposomal doxorubicin compared to doxorubicin.
Also, myelosuppression with doxorubicin is considerably more substantial compared to that observed with the liposomal drug formulation.
Two side effects appear unique to the pegylated liposomal doxorubicin form:
(1) Risk for hand-foot syndrome.
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(2) Acute infusion reaction.
The acute infusion reaction, dependent on infusion rate, presents with the following:
Flushing
Dyspnea
Fever
Edema
Chills
Bronchospasm
Rash Hypertension.
FDA-approved
uses for pegylated liposomal doxorubicin (Doxil) include:
Ovarian cancer
AIDS-related Kaposi's sarcoma
Multiple myeloma.7
Pharmacokinetics and toxicities:
In preclinical experiments, liposomal doxorubicin elimination was characterized by a one-or two-phase plasma concentration-time curve.
Drug elimination was characterized by half-life of about 25 hours.
The volume of distribution (Vd) approximated blood volume.
Tissue distribution studies suggested preferential concentration of drug in tumor, compared with free doxorubicin (non-pegylated liposomal form).
Pegylated liposomal doxorubicin has been the subject of clinical trials in patients with a variety of solid tumors including breast, ovarian and prostate carcinoma, well as in patients with AIDS-related Kaposi's sarcoma (ARKS).
Pharmacokinetic profiles determined in human subjects appeared similar to that observed in animals within a dose range of 10-80 mg/m2.
Toxicity of
pegylated liposomal doxorubicin includes both dose-limiting mucosal and cutaneous
toxicityand mild myelosuppression and reduced cardiotoxicity
(compared with free doxorubicin) described earlier.
Despite
mucocutaneous toxic reactions to liposomal doxorubicin, the reduced
cardiotoxicity of the liposomal form permits an increased cumulative dose
compared to free doxorubicin dosing.
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