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

临床前和临床经验表明， 干扰素抑制HIV复制并具有抗肿瘤活性 Kaposius肉瘤（KS）。 在这项研究中，干扰素- α-2b（IFN-a）和9-顺式视黄酸（9-cRA）将被检测， 确定最大耐受剂量（MTD）和剂量限制性毒性 (DLT)艾滋病相关KS患者的治疗效果。 最小 将研究6名患者，最多24名患者。 患者将 以25 mg/m2/天的起始剂量给予9-cRA（ALRT 1057，NSC #659772）。 在指定的剂量水平内，9-cRA的剂量不会递增。 9-cRA将在治疗的前7天单独给药。 从第8天开始，患者将被给予IFN-a。 患者将 在给定剂量水平下观察至少四周， 进入下一个剂量水平。 此外，该研究还将评估 在这些患者中的以下情况：1）各种亚型的水平 视黄酸受体（RAR）、类维生素A X受体（RXR）和类维生素A 孤儿受体（ROR/RZR）mRNA和蛋白质在KS组织中获得2-mm 9-cRA/IFN-α治疗前和治疗期间的穿刺活检 组合; 2）9-cRA和IFN-α的药代动力学; 3）9-cRA和IFN-α的组合。 9-cRA和IFN-a对HIV活性的影响;和4）抗肿瘤 9-cRA和IFN-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.