Topical DMSO treatment for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia

Purpose: Chemotherapeutic regimens that utilize fluorouracil, cytarabine, and doxorubicin have been shown to cause a dermatologic syndrome known as hand-foot syndrome, or palmar-plantar erythrodysesthesia syndrome (PPES). Pegylated liposomal doxorubicin has proven effective in the treatment of AIDS-related Kaposi's sarcoma, ovarian cancer refractory to platinum and paclitaxel therapies, and metastatic breast cancer. In a study of the treatment of refractory epithelial cell ovarian cancers with lipozomal doxorubicin utilizing intravenous doses of 50 mg/m² every 3 weeks, grade 3 PPES was observed in 29% of patients (10/35) and required dose reductions and/or dose delay after a median of three therapy cycles. Methods: Current methods to prevent pegylated liposomal doxorubicin-induced PPES include dose reduction, lengthening of the drug administration interval and ultimately, drug withdrawal. Topical 99% dimethylsulfoxide (DMSO) also has shown strong activity in treating tissue extravasation reactions during intravenous administration of doxorubicin. Results: Two patients undergoing chemotherapy with pegylated liposomal doxorubicin, 50 mg/m² every 4 weeks, developed grade 3 PPE after three cycles. Their PPES resolved over a period of 1 to 3 weeks while receiving topical 99% DMSO four times daily for 14 days. Conclusions: While these results are promising, patients must be treated in a prospective study of this topical DMSO formulation to definitively document its therapeutic efficacy.