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

大剂量化疗引起的血小板减少仍然是一个重要的 限制许多化疗剂量强化的临床问题 剂. 在我们的IL-1 α I期试验中，我们注意到， 骨髓中的巨核细胞和血小板计数增加 IL-1 α治疗后。 我们设计这个试验是为了确定 IL-1 α可改善化疗所致的血小板减少。 我们选择卡铂与IL-1 α联合联合收割机， 相当大的抗肿瘤活性，但受骨髓 抑制，尤其是血小板减少症。 本研究共招募了52名 患者至今 11名患者属于对照组， 卡铂单药（800 mg/m2）。5例患者接受IL-1 α治疗 卡铂剂量分别为0.03、0.1和0.3 μ g/kg。 5名患者接受 0.03 11名患者接受卡铂治疗后， 0.1 IL-1 α，10例患者接受0.3 μ g/kg 卡铂后的IL-1 α。 本试验中观察到的毒性为 类似于先前单独使用任一种药物的试验所观察到的那些。 卡铂后IL-1 α治疗显著促进血小板聚集 在0.3%时， μ g/kg IL-1 α剂量。 在高剂量之前用IL-Ia治疗 卡铂没有效果。 15个病人中有5个在两个最高的 卡铂后给予的IL-1 α剂量具有极轻微的血小板减少症。 IL-1 α治疗导致血清中IL-1 α水平的剂量相关性增加， IL-6和G-CSF。 该试验提供了结论性证据， 治疗可以显著改善化疗诱导的 血小板减少症

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 52 patients to date. Eleven patients were in a control group and received carboplatin alone (800 mg/m2). Five patients each received IL-1alpha before carboplatin at 0.03, 0.1 and 0.3 mu-g/kg. Five patients received 0.03 mu-g/kg IL-1alpha after carboplatin and 11 patients each received 0.1 IL-1alpha after carboplatin and 10 patients received 0.3 mu-g/kg IL-1alpha after carboplatin. Toxicities observed in this trial were similar to those observed with previous trials of either agent alone. IL-1alpha treatment after carboplatin significantly accelerated platelet recovery and shortened the duration of severe thrombocytopenia at the 0.3 mu-g/kg IL-1alpha dose. Treatment with IL-la before high dose carboplatin had no effect. Five of 15 patients at the two highest IL-1alpha doses given after carboplatin had minimal thrombocytopenia. IL-1alpha treatment produced dose related increases in the serum level of IL-6 and G-CSF. This trial provides conclusive evidence that IL-1alpha treatment can significantly ameliorate chemotherapy induced thrombocytopenia.