Coukell A J, Spencer C M
Adis International Limited, Auckland, New Zealand.
Drugs. 1997 Mar;53(3):520-38. doi: 10.2165/00003495-199753030-00011.
Doxorubicin is an antineoplastic drug which has in vitro and in vivo activity against a number of malignancies including Kaposi's sarcoma. Incorporation of doxorubicin into polyethylene glycol-coated (pegylated) liposomes alters the pharmacokinetics of the drug. Liposomal doxorubicin has a smaller volume of distribution and slower plasma clearance than standard free doxorubicin. The liposomal formulation achieves higher concentrations in the highly vascularised lesions of Kaposi's sarcoma than in normal tissue. Liposomal doxorubicin monotherapy in patients with AIDS-related Kaposi's sarcoma produced overall response rates (complete plus partial) of 43 and 59% in large comparative studies and 67 to 100% in noncomparative studies which included > or = 20 patients. In comparative studies, liposomal doxorubicin was significantly more effective than the combination of standard doxorubicin, bleomycin and vincristine (overall response rates of 43 and 25%, respectively) and bleomycin and vincristine (BV) [overall response rates of 59 and 23%, respectively]. In addition, overall response rates to the liposomal drug were higher in both treatment arms of 2 smaller comparative studies which compared liposomal doxorubicin with BV, but significant between-treatment differences were not detected. Patient numbers in these 2 studies, however, may have been too small to detect significant differences. Liposomal doxorubicin is generally well tolerated. Myelosuppression is the most common dose-limiting adverse effect in patients with AIDS and Kaposi's sarcoma. Neutropenia occurs most often; anaemia and thrombocytopenia occur less frequently, as do nausea and vomiting and stomatitis. Palmar-plantar erythrodysaesthesia occurs in some patients, most commonly after 6 to 8 weeks of chemotherapy. Although symptoms may occasionally be severe, the syndrome usually does not require dosage reduction or treatment delay. Limited data suggest that the incidence of cardiotoxicity may be lower after liposomal doxorubicin than after equivalent doses of standard doxorubicin. Overall, liposomal doxorubicin appears to be one of the most active single agents available for treating patients with AIDS-related Kaposi's sarcoma. The therapeutic potential of liposomal doxorubicin administered in combination with other active agents to patients with Kaposi's sarcoma is, as yet, unknown. However, administered alone, the drug seems to be more effective than the best available combination chemotherapy regimens.
阿霉素是一种抗肿瘤药物，它在体外和体内对包括卡波西肉瘤在内的多种恶性肿瘤都有活性。将阿霉素包封于聚乙二醇包被（聚乙二醇化）的脂质体中可改变该药物的药代动力学。与标准游离阿霉素相比，脂质体阿霉素的分布容积更小，血浆清除率更慢。脂质体制剂在卡波西肉瘤高度血管化的病灶中比在正常组织中能达到更高的浓度。在大型对比研究中，脂质体阿霉素单药治疗艾滋病相关卡波西肉瘤患者的总体缓解率（完全缓解加部分缓解）为43%和59%，在纳入≥20例患者的非对比研究中为67%至100%。在对比研究中，脂质体阿霉素显著比标准阿霉素、博来霉素和长春新碱联合用药（总体缓解率分别为43%和25%）以及博来霉素和长春新碱（BV）联合用药（总体缓解率分别为59%和23%）更有效。此外，在两项将脂质体阿霉素与BV进行比较的较小对比研究的两个治疗组中，对脂质体药物的总体缓解率均更高，但未检测到显著的组间差异。然而，这两项研究中的患者数量可能太少，无法检测到显著差异。脂质体阿霉素一般耐受性良好。骨髓抑制是艾滋病和卡波西肉瘤患者中最常见的剂量限制性不良反应。中性粒细胞减少最常发生；贫血和血小板减少较少发生，恶心、呕吐和口腔炎也是如此。一些患者会出现手足红斑感觉异常，最常见于化疗6至8周后。虽然症状偶尔可能很严重，但该综合征通常不需要降低剂量或延迟治疗。有限的数据表明，脂质体阿霉素治疗后心脏毒性的发生率可能低于同等剂量标准阿霉素治疗后。总体而言，脂质体阿霉素似乎是可用于治疗艾滋病相关卡波西肉瘤患者的最有效的单一药物之一。脂质体阿霉素与其他活性药物联合应用于卡波西肉瘤患者的治疗潜力目前尚不清楚。然而，单独使用时，该药物似乎比现有的最佳联合化疗方案更有效。
