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Skin Toxic Effects of Polyethylene Glycol–Coated Liposomal Doxorubicin
Michal Lotem, MD;
Ayala Hubert, MD;
Olga Lyass, MD;
Michael A. Goldenhersh, MD;
Arieh Ingber, MD;
Tamar Peretz, MD;
Alberto Gabizon, MD, PhD
Arch Dermatol. 2000;136:1475-1480.
Objectives To record the profile of toxic effects of polyethylene glycol–coated liposomal doxorubicin hydrochloride (Doxil) to the skin, and to evaluate whether the long circulation pattern and enhanced accumulation of liposomes in specific skin sites will result in any unique presentations.
Design Patients were accrued in the frame of dose-range–finding studies that examine the toxic effects and antitumor activity of Doxil therapy in metastatic breast and prostate cancers. All patients receiving Doxil were instructed to report any skin eruption or discomfort. Skin examination was performed on a regular basis at every cycle of Doxil therapy and after specific complaints.
Setting Outpatient day care unit of the oncology institute of a secondary-referral medical center.
Patients Sixty patients (45 women and 15 men).
Main Outcome Measures A basic severity scale of I through IV was adopted for toxic effects to the skin, based on National Cancer Institute common toxicity criteria.
Results The following 4 patterns of skin eruptions were encountered: hand-foot syndrome (n = 24), diffuse follicular rash (n = 6), intertrigolike eruption (n = 5), and new formation of melanotic macules (n = 3). Another major toxic effect of Doxil was stomatitis, which was found to be the dose-limiting factor for the maximal single dose. Alopecia and extravasation injuries did not occur.
Conclusions The profile of toxic effects of Doxil to the skin reflects its unique pharmacokinetics and tissue distribution. These skin reactions vary significantly from those associated with doxorubicin in non–liposome-encapsulated form.
From the Sharett Institute of Oncology (Drs Lotem, Hubert, Lyass, Peretz, and Gabizon) and the Departments of Dermatology (Drs Lotem, Goldenhersh, and Ingber) and Pathology (Dr Goldenhersh), Hadassah Hebrew University Medical Center, Jerusalem, Israel.
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