PHASE I PHARMACOKINETIC STUDY OF IL-2 ENCAPSULATED IN LIPOSOMES

IL-2是一种有效的治疗方法， 黑素瘤或肾细胞癌。其他癌症的治疗方法 不太成功，所有患者的治疗都可能受到严重的 全身毒性，特别是在高剂量IL-2下。的封装 IL-2脂质体可允许以目前有效的剂量治疗患者。 剂量毒性较小，或可能导致疗效改善， 增加可以安全施用的IL-2的剂量。也是 脂质体IL-2在某些器官中的积累可能 导致对这些部位转移更有效的治疗。我们有 启动了脂质体包封的IL-2在患者中的Ia/Ib期研究 晚期癌症患者 脂质体IL-2通过30分钟静脉输注给药， 第一周，第二周三次，第五周五次 三. 有效患者有资格接受额外治疗。 在 除了对治疗的反应外，还监测患者的毒性， 继发于治疗的免疫学变化。 22名患者 接受过以下剂量水平的治疗：1 × 10（6）u/m2; 3 × 10（6）u/m2; 4.5x10（6）u/m2和6x 10（6）u/m2。 剂量限制性毒性尚未得到证实。 观察到患者继续增加较高剂量水平。 那里 有两个部分回应和两个次要回应。 纳戈尔诺-卡拉巴赫增加 活性和血清可溶性IL-2受体水平已经注意到， 大于或等于4.5x10（6）u/m2。

IL-2 is effective treatment for a significant minority of patients with melanoma or renal cell cancer. Treatment of other cancers has been much less successful, and treatment of all patients can be limited by severe systemic toxicity particularly at high doses of IL-2. The encapsulation of IL-2 liposomes may permit treatment of patients at currently effective doses with less toxicity, or it may lead to improved efficacy by increasing the dose of IL-2 that can be administered safely. It is also possible that the accumulation of liposomal IL-2 in certain organs will lead to more effective therapy of metastases to these sites. We have initiated a phase Ia/lb study of liposome-encapsulated IL-2 in patients with advanced cancer. Liposomal IL-2 is given by 30 min. IV infusion on during week one, three times during week two and five times during week three. Responding patients are eligible for additional therapy. In addition to response to therapy, patients are monitored for toxicity and for immunologic changes secondary to treatment. Twenty-two patient have been treated at the following dose levels: 1x 10(6) u/m2; 3x10(6) u/m2; 4.5x10(6) u/m2 an 6x10(6) u/m2. Dose-limiting toxicity has not been observed and accrual of patients continues a higher dose levels. There have been two partial responses and two minor responses. Increases in NK activity and serum soluble IL-2 receptor levels have been noted at doses of greater than or equal to 4.5x10(6) u/m2.