Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer.
Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer.
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DOI：
10.1016/j.radonc.2016.04.013
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Chakravarthy AB
中科院分区：
文献类型：
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作者：
Chan E;Arlinghaus LR;Cardin DB;Goff L;Berlin JD;Parikh A;Abramson RG;Yankeelov TE;Hiebert S;Merchant N;Bhaskara S;Chakravarthy AB
这项单机构I期试验确定了非转移性胰腺癌患者同时接受伏立诺他和卡培他滨联合放疗的最大耐受剂量（MTD）。21名患者在放疗期间接受了剂量不断增加的伏立诺他（每天100-400毫克）。卡培他滨1000 mg q12在放射日给药。放疗剂量为30戈伊，分10次。伏立诺他剂量递增遵循标准3 + 3设计。未计划剂量递增超过400 mg伏立诺他。治疗前和治疗后的弥散加权（DW）-MRI用于评价体内肿瘤细胞构成。伏立诺他的MTD为400 mg。在100 mg、300 mg和400 mg剂量水平下各有1例患者发生剂量限制性毒性：2例胃肠道毒性和1例血小板减少症。最常见的不良事件是淋巴细胞减少症（76%）和恶心（14%）。表观扩散系数（ADC）在大多数肿瘤中增加。19例（90%）患者病情稳定，2例（10%）患者在手术时病情进展。11例患者接受了手术探查，其中4例R 0切除，1例R1切除。中位总生存期为1.1年（95%置信区间为0.78-1.35）。伏立诺他400 mg每日M-F和卡培他滨1000 mg q12 M-F联合放疗（30戈伊，分10次）耐受性良好，中位总生存期令人鼓舞。
This single institution phase I trial determined the maximum tolerated dose (MTD) of concurrent vorinostat and capecitabine with radiation in non-metastatic pancreatic cancer. Twenty-one patients received escalating doses of vorinostat (100–400 mg daily) during radiation. Capecitabine was given 1000 mg q12 on the days of radiation. Radiation consisted of 30 Gy in 10 fractions. Vorinostat dose escalation followed the standard 3 + 3 design. No dose escalation beyond 400 mg vorinostat was planned. Diffusion-weighted (DW)-MRI pre- and post-treatment was used to evaluate in vivo tumor cellularity. The MTD of vorinostat was 400 mg. Dose limiting toxicities occurred in one patient each at dose levels 100 mg, 300 mg, and 400 mg: 2 gastrointestinal toxicities and one thrombocytopenia. The most common adverse events were lymphopenia (76%) and nausea (14%). The apparent diffusion coefficient (ADC) increased in most tumors. Nineteen (90%) patients had stable disease, and two (10%) had progressive disease at time of surgery. Eleven patients underwent surgical exploration with four R0 resections and one R1 resection. Median overall survival was 1.1 years (95% confidence interval 0.78–1.35). The combination of vorinostat 400 mg daily M–F and capecitabine 1000 mg q12 M–F with radiation (30 Gy in 10 fractions) was well tolerated with encouraging median overall survival.