Gill P S
Department of Internal Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Semin Oncol. 1991 Oct;18(5 Suppl 7):53-7.
Kaposi's sarcoma (KS) is a malignant neoplasm that develops in 20% to 30% of all acquired immunodeficiency syndrome (AIDS) cases. Kaposi's sarcoma primarily involves the skin, but can progress to involve the lungs, gastrointestinal tract, and liver. alpha-Interferon alone or in combination with zivoduvine has activity in acquired immunodeficiency syndrome-related KS, especially in patients with limited disease and CD4 lymphocyte counts over 400/mm3. Patients with progressive or symptomatic visceral disease, however, can be treated more effectively with cytotoxic chemotherapy. We have used a combination of doxorubicin, bleomycin, and vincristine (ABV) and have achieved response rates of over 80%. Discontinuation of therapy, however, is associated with relapse shortly after response (2 to 3 months). Thus, we have begun studies to define a safe and effective maintenance therapy. Such therapies should include antiretroviral agents since most patients succumb to other human immunodeficiency virus complications, and since human immunodeficiency virus directly, through viral proteins, and indirectly, through the induction of cellular genes, induces KS growth. Additionally, agents with antitumor activity and possible antiviral activity, such as alpha-interferon, may be potentially effective in maintenance therapies. We recently studied 21 patients in a phase I study of recombinant interferon alpha-2b (INTRON-A, Schering-Plough Corp, Kenilworth, NJ) alone following ABV chemotherapy. A dose of 10 million units, given in daily subcutaneous injections, was the maximal tolerated dose; higher doses were associated with intolerable fatigue, diarrhea, and fevers. We are currently conducting a phase I/II trial studying the combination of zivoduvine (500 mg/d) and recombinant interferon alpha-2b (5, 10, and 15 million units) as maintenance in patients with advanced or progressive KS.
卡波西肉瘤（KS）是一种恶性肿瘤，在所有获得性免疫缺陷综合征（AIDS）病例中，有20%至30%会发生。卡波西肉瘤主要累及皮肤，但可进展至累及肺部、胃肠道和肝脏。单独使用α干扰素或与齐多夫定联合使用，对与获得性免疫缺陷综合征相关的卡波西肉瘤有活性，特别是对于疾病局限且CD4淋巴细胞计数超过400/mm³的患者。然而，对于进展性或有症状的内脏疾病患者，细胞毒性化疗可能更有效。我们使用了阿霉素、博来霉素和长春新碱（ABV）联合治疗，有效率超过80%。然而，停止治疗后，缓解后不久（2至3个月）就会复发。因此，我们已开始研究确定一种安全有效的维持治疗方法。此类治疗应包括抗逆转录病毒药物，因为大多数患者死于其他人类免疫缺陷病毒并发症，而且人类免疫缺陷病毒通过病毒蛋白直接以及通过诱导细胞基因间接诱导卡波西肉瘤生长。此外，具有抗肿瘤活性和可能抗病毒活性的药物，如α干扰素，可能在维持治疗中具有潜在疗效。我们最近在一项I期研究中，对21例患者在ABV化疗后单独使用重组干扰素α-2b（INTRON-A，先灵葆雅公司，新泽西州肯尼沃思）进行了研究。每日皮下注射1000万单位的剂量是最大耐受剂量；更高剂量会导致无法耐受的疲劳、腹泻和发热。我们目前正在进行一项I/II期试验，研究齐多夫定（500mg/天）和重组干扰素α-2b（500万、1000万和1500万单位）联合用于晚期或进展性卡波西肉瘤患者的维持治疗。
