Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553).
Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553).
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蛋白酶体抑制剂carfilzomib用伊立替康（Irinotecan）在肺癌和其他对先前治疗方面进展的伊诺特坎敏感性恶性肿瘤的1B试验（Onyx IST参考号：CAR-IST-553）。
DOI：
10.1007/s10637-017-0441-4
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发表时间：
2017-10
影响因子：
3.4
通讯作者：
Baggstrom MQ
中科院分区：
文献类型：
--
作者：
Arnold SM;Chansky K;Leggas M;Thompson MA;Villano JL;Hamm J;Sanborn RE;Weiss GJ;Chatta G;Baggstrom MQ
蛋白酶体抑制剂是一种治疗多种恶性肿瘤的有效方法。卡非佐米是一种新型蛋白酶体抑制剂，与伊立替康联合使用，为复发性伊立替康敏感性癌症提供了一种协同方法。材料和方法复发性伊立替康敏感性癌症患者接受三种剂量水平（20/27 mg/m2、20/36 mg/m2和20/45 mg/m2/天）的卡非佐米（第1、2、8、9、15和16天）与125 mg/m2/天的伊立替康（第1、8和15天）联合治疗。关键合格性标准包括可测量的疾病、Zubrod PS为0或1以及可接受的器官功能。稳定无症状脑转移患者符合条件。剂量递增采用标准3 + 3设计。结果总体而言，16例患者入组3个剂量水平，4例患者被替换。3例患者发生剂量限制性毒性（DLT），队列3中超过了最大耐受剂量（MTD）。RP 2剂量为卡非佐米20/36 mg/m2（第1、2、8、9、15和16天给药）和伊立替康125 mg/m2（第1、8和15天）。常见的3级和4级毒性包括疲乏（19%）、血小板减少症（19%）和腹泻（13%）。结论伊立替康和卡非佐米耐受性良好，常见毒副反应为疲乏、血小板减少和血小板减少性发热。客观临床缓解率为19%（小细胞肺癌（SCLC）中1例确认部分缓解（PR），2例未确认）;疾病控制率（DCR）为25%时，疾病稳定（SD）为6%。推荐的II期剂量为卡非佐米20/36 mg/m2和伊立替康125 mg/m2。II期评估正在复发性小细胞肺癌中进行。
Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day. Key eligibility criteria included measurable disease, a Zubrod PS of 0 or 1, and acceptable organ function. Patients with stable asymptomatic brain metastases were eligible. Dose escalation utilized a standard 3 + 3 design. Results Overall, 16 patients were enrolled to three dose levels, with four patients replaced. Three patients experienced dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) was exceeded in Cohort 3. The RP2 dose was carfilzomib 20/36 mg/m2 (given on Days 1, 2, 8, 9, 15, and 16) and irinotecan 125 mg/m2 (Days 1, 8 and 15). Common Grade (Gr) 3 and 4 toxicities included fatigue (19%), thrombocytopenia (19%), and diarrhea (13%). Conclusions Irinotecan and carfilzomib were well tolerated, with common toxicities of fatigue, thrombocytopenia and neutropenic fever. Objective clinical response was 19% (one confirmed partial response (PR) in small cell lung cancer (SCLC) and two unconfirmed); stable disease (SD) was 6% for a disease control rate (DCR) of 25%. The recommended phase II dose was carfilzomib 20/36 mg/m2 and irinotecan125 mg/m2. The phase II evaluation is ongoing in relapsed small cell lung cancer.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
4.6
作者：
Denlinger, CE;Rundall, BK;Jones, DR
通讯作者：
Jones, DR
影响因子：
45.3
作者：
FUKUOKA, M;NIITANI, H;MIYATA, Y
通讯作者：
MIYATA, Y
影响因子：
11.2
作者：
Demo, Susan D.;Kirk, Christopher J.;Bennett, Mark K.
通讯作者：
Bennett, Mark K.
影响因子：
20.3
作者：
Kuhn, Deborah J.;Chen, Qing;Orlowski, Robert Z.
通讯作者：
Orlowski, Robert Z.