9-CIS RETINOIC ACID/INTERFERON-ALPHA 2B IN AIDS-ASSOCIATED KAPOSI'S SARCOMA

临床前和临床经验表明，维甲酸和 干扰素抑制HIV复制并具有抗肿瘤活性 卡波修斯肉瘤(KS)。在这项研究中，干扰素- 将检测α-2b(干扰素-a)和9-顺式维甲酸(9-CRA)以 确定最大耐受量(MTD)和剂量限制毒性 (DLT)这种疗法在艾滋病相关KS患者中的应用。最低要求 将对6名和最多24名患者进行研究。病人将会是 给予9-CRA(ALRT1057，NSC编号659772)，起始剂量为25 mg/m2/d。 在指定的剂量水平内，9-CRA不会发生剂量增加。 在治疗的前7天，9-CRA将单独给予。 从第8天开始，患者将接受干扰素-a治疗。病人将会是 在给定剂量水平观察至少四周之前 进入下一个剂量级别。此外，该研究还将评估 这些患者的下列指标：1)各亚型的水平 维甲酸受体(RAR)、维甲酸X受体(RXR)和维甲酸 2-mM法获得KS组织孤儿受体(ROR/RZR)mRNA和蛋白 9-CRA/干扰素-a治疗前和治疗中的穿孔活检 2)9-CRA和干扰素-α的药代动力学；3) 9-CRA和干扰素-α对HIV活性的影响；4)抗肿瘤 9-CRA和干扰素-α的作用。

Preclinical and clinical experience suggests that both retinoids and interferon inhibit HIV replication and have anti-tumor activity against KaposiUs sarcoma (KS). In this study, the combination of interferon- alpha-2b (IFN-a) and 9-cis retinoic acid (9-cRA) will be tested to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy in patients with AIDS-associated KS. A minimum of 6 and a maximum of 24 patients will be studied. Patients will be given 9-cRA (ALRT1057, NSC #659772) at a starting dose of 25 mg/m2/day. No dose escalation of 9-cRA will occur within a designated dose level. The 9-cRA will be given alone for the first 7 days of therapy. Beginning on day 8, patients will be given IFN-a. Patients will be observed at a given dose level for a minimum of four weeks before proceeding to the next dose level. In addition, the study will assess the following in these patients: 1) the levels of the various subtypes of retinoic acid receptor (RAR), retinoid X receptor (RXR), and retinoid orphan receptor (ROR/RZR) mRNA and protein in KS tissue obtained by 2-mm punch biopsy prior to and during therapy with the 9-cRA/IFN-a combination; 2) the pharmacokinetics of 9-cRA and IFN-a; 3) the effects of 9-cRA and IFN-a on HIV activity; and 4) the antitumor effects of 9-cRA and IFN-a.