硼替佐米、依托泊苷及卡铂用于对标准治疗难治的晚期实体瘤患者的I期研究。
A phase I study of bortezomib, etoposide and carboplatin in patients with advanced solid tumors refractory to standard therapy.
作者信息
Lieu Christopher, Chow Laura, Pierson A Scott, Eckhardt S Gail, O'Bryant Cindy L, Morrow Mark, Tran Zung Vu, Wright John J, Gore Lia
机构信息
University of Colorado Cancer Center, 1665 North Ursula Street, Aurora, CO, USA.
出版信息
Invest New Drugs. 2009 Feb;27(1):53-62. doi: 10.1007/s10637-008-9154-z. Epub 2008 Jul 11.
PURPOSE
To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies.
PATIENTS AND METHODS
Patients received escalating doses of bortezomib, etoposide, and carboplatin every 21 days. Surrogate markers of angiogenesis were evaluated.
RESULTS
Twenty-four patients received 64 courses of therapy. The most common treatment-related adverse events were myelosuppression. Dose-limiting grade 3 and 4 neutropenia and thrombocytopenia were observed when bortezomib was given on days 1, 4, 8, 11. With revised dosing, the maximum tolerated dose (MTD) of bortezomib 0.75 mg/m(2) (days 1, 8), etoposide 75 mg/m(2) (days 1-3), and carboplatin AUC 5 (day 1) was well tolerated, and are the recommended doses for further studies with this combination. No objective responses were observed, however stable disease was noted for greater or equal to four cycles in nine highly refractory patients.
目的
评估硼替佐米、依托泊苷与卡铂联合用药对晚期实体恶性肿瘤成人患者的毒性、药理及生物学特性。
患者与方法
患者每21天接受递增剂量的硼替佐米、依托泊苷与卡铂治疗。对血管生成的替代标志物进行评估。
结果
24例患者接受了64个疗程的治疗。最常见的治疗相关不良事件为骨髓抑制。当在第1、4、8、11天给予硼替佐米时，观察到剂量限制性3级和4级中性粒细胞减少及血小板减少。经调整给药方案后，硼替佐米0.75mg/m²（第1、8天）、依托泊苷75mg/m²（第1 - 3天）及卡铂曲线下面积（AUC）5（第1天）的最大耐受剂量（MTD）耐受性良好，是该联合用药进一步研究的推荐剂量。未观察到客观缓解，但9例高度难治性患者病情稳定达4个或更多周期。
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