Lopez A M, Wallace L, Dorr R T, Koff M, Hersh E M, Alberts D S
Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Cancer Chemother Pharmacol. 1999;44(4):303-6. doi: 10.1007/s002800050981.
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/m(2) 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.
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.
Two patients undergoing chemotherapy with pegylated liposomal doxorubicin, 50 mg/m(2) 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.
While these results are promising, patients must be treated in a prospective study of this topical DMSO formulation to definitively document its therapeutic efficacy.
已证明使用氟尿嘧啶、阿糖胞苷和多柔比星的化疗方案会引发一种称为手足综合征或掌跖红斑感觉异常综合征（PPES）的皮肤病综合征。聚乙二醇化脂质体多柔比星已被证明对治疗艾滋病相关的卡波西肉瘤、铂类和紫杉醇治疗难治的卵巢癌以及转移性乳腺癌有效。在一项使用脂质体多柔比星治疗难治性上皮细胞卵巢癌的研究中，每3周静脉注射剂量为50mg/m²，29%的患者（10/35）出现3级PPES，在中位三个治疗周期后需要降低剂量和/或延迟给药。
目前预防聚乙二醇化脂质体多柔比星诱导的PPES的方法包括降低剂量、延长给药间隔，最终停药。局部使用99%二甲基亚砜（DMSO）在多柔比星静脉给药期间治疗组织外渗反应方面也显示出强大活性。
两名接受聚乙二醇化脂质体多柔比星化疗（每4周50mg/m²）的患者在三个周期后出现3级PPE。他们的PPES在每天4次局部使用99%DMSO共14天的情况下，在1至3周内得到缓解。
虽然这些结果很有前景，但必须在这项局部DMSO制剂的前瞻性研究中对患者进行治疗，以明确记录其治疗效果。
