The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB1-1M59, Baltimore, MD 21231, USA.
Cancer Chemother Pharmacol. 2011 Feb;67(2):431-8. doi: 10.1007/s00280-010-1328-7. Epub 2010 May 6.
To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors.
This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m(2) given on Day 1 of each 21-day cycle.
OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response.
The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued.
确定 OSI-461 与米托蒽醌联合用于治疗晚期实体瘤患者的最大耐受剂量（MTD）。
这是一项 I 期研究，采用 OSI-461 口服每日两次递增剂量与米托蒽醌 12mg/m²（第 1 天，每 21 天为一个周期）联合治疗。
OSI-461 的剂量递增至 1000mg，每日两次。1 名患者出现剂量限制性毒性（DLT）。3 名患者因不良事件（AE）退出研究。2 名患者（10%）有部分缓解，10 名患者（50%）的最佳缓解为疾病稳定。
OSI-461 与米托蒽醌联合使用耐受性良好。由于同期进行的 I 期试验出现毒性，因此停止了剂量递增。在前列腺癌患者中观察到的缓解率与米托蒽醌和泼尼松单独治疗的试验中观察到的缓解率相当，因此未进一步研究 OSI-461 与米托蒽醌的联合用药。
