PHASE I STUDY OF HIGH DOSE CARBOPLATIN PLUS IL-1 ALPHA.

大剂量化疗所致的血小板减少症仍是一个显著的问题 限制许多化疗剂量强化的临床问题 探员们。在我们的IL-1αI期试验中，我们注意到增加了 骨髓中的巨核细胞和血小板计数的增加 经IL-1α治疗后。我们设计这次试验是为了确定 IL-1α是否能改善小鼠血小板减少症 化疗。我们选择卡铂与IL-1α联合使用是因为它 具有相当大的抗肿瘤活性，但受到骨髓的限制 抑制，尤指血小板减少症。这项研究已经招募了27人 到目前为止的病人。7名患者为对照组，接受了 单用卡铂(800 mg/m2)。10例患者接受了0.03%的IL-1α治疗 微克/千克和10微克/千克白介素1α治疗一半患者 卡铂(800 mg/m2)前、后各半次接受IL-1α治疗。 在这项试验中观察到的毒性与 之前对任何一种药物的单独试验。IL-1α治疗似乎对 减轻了一些患者的血小板减少程度，但这 在前两个剂量水平上并没有一致地观察到效果 IL-1α的表达。10名IL-1α剂量最高的患者入选 (0.3微克/公斤)将在不久的将来完成。如果IL-1α 治疗减轻卡铂的骨髓抑制，第二个 这项研究的一部分将确定IL-1α可以增加到什么程度 卡铂的剂量强度。

Thrombocytopenia induced by high-dose chemotherapy remains a significant clinical problem that limits dose intensification of many chemotherapy agents. In our phase I trial of IL-1alpha, we noted increased megakaryocytes in the bone marrow and an increase in the platelet count after IL-1alpha treatment. We designed the present trial to determine if IL-1alpha could ameliorate the thrombocytopenia induced by chemotherapy. We chose carboplatin to combine with IL-1alpha because it has considerable antitumor activity, but is limited by bone marrow suppression, especially thrombocytopenia. This study has enrolled 27 patients to date. Seven patients were in a control group and received carboplatin alone (800 mg/m2). Ten patients received IL-1alpha at 0.03 mcg/kg and ten received 0.1 mcg/kg IL-1alpha with half the patients receiving IL-1alpha before and half after carboplatin (800 mg/m2). Toxicities observed in this trial were similar to those observed with previous trials of either agent alone. IL-1alpha treatment appears to have lessened the degree of thrombocytopenia in some patients, but this effect has not been consistently observed at the first two dose levels of IL-1alpha. Enrollment of 10 patients at the highest IL-1alpha dose (0.3 micro g/kg) will be completed in the near future. If IL-1alpha treatment lessens the bone marrow suppression of carboplatin, a second part of this study will determine to what extent IL-1alpha can increase the dose intensity of carboplatin.