Bendell Johanna C, Jones Suzanne F, Hart Lowell, Pant Shubham, Moyhuddin Adil, Lane Cassie M, Earwood Chris, Murphy Patrick, Patton Jeffrey, Penley William C, Thompson Dana, Infante Jeffrey R
a Sarah Cannon Research Institute/Tennessee Oncology , PLLC, Nashville , Tennessee , USA.
b Sarah Cannon Research Institute , Nashville , Tennessee , USA.
Cancer Invest. 2015;33(10):477-82. doi: 10.3109/07357907.2015.1069834. Epub 2015 Oct 13.
This phase I study determined the maximum tolerated dose (MTD) of AUY922 with capecitabine in advanced solid tumors.
Capecitabine 1000 mg/m(2) PO BID was administered with escalating doses of AUY922 IV; the MTD of AUY922 was combined with capecitabine 1250 mg/m(2) (DL6).
23 patients were treated at 5 dose levels (22 mg/m(2)-70 mg/m(2)). No DLTs were observed until DL6 (grade 3 diarrhea). Reversible vision darkening was seen in 26%. Four patients had partial response; 2 previously progressed on fluorouracil. Eight patients had stable disease (median 25.5 weeks).
AUY922 plus capecitabine was well-tolerated up to 70 mg/m(2) with encouraging preliminary efficacy.
本I期研究确定了AUY922与卡培他滨联合用于晚期实体瘤的最大耐受剂量（MTD）。
口服卡培他滨1000 mg/m²，每日两次，同时静脉注射递增剂量的AUY922；AUY922的MTD与卡培他滨1250 mg/m²（剂量水平6）联合使用。
23例患者在5个剂量水平（22 mg/m² - 70 mg/m²）接受治疗。在剂量水平6之前未观察到剂量限制性毒性（DLT）（3级腹泻）。26%的患者出现可逆性视力模糊。4例患者部分缓解；其中2例之前对氟尿嘧啶治疗进展。8例患者病情稳定（中位时间25.5周）。
AUY922加卡培他滨在高达70 mg/m²的剂量下耐受性良好，初步疗效令人鼓舞。
