A phase 2 study of oral MKC-1, an inhibitor of importin-β, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer.
A phase 2 study of oral MKC-1, an inhibitor of importin-β, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer.
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DOI：
10.1007/s10637-011-9708-3
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发表时间：
2012-08
影响因子：
3.4
通讯作者：
Kwak, Eunice L.
中科院分区：
文献类型：
--
作者：
Faris, Jason E.;Arnott, Jamie;Zheng, Hui;Ryan, David P.;Abrams, Thomas A.;Blaszkowsky, Lawrence S.;Clark, Jeffrey W.;Enzinger, Peter C.;Hezel, Aram F.;Ng, Kimmie;Wolpin, Brian M.;Kwak, Eunice L.
MKC-1是一种口服细胞周期抑制剂，其下游靶点包括微管蛋白和importin-β家族。我们在晚期胰腺癌患者中进行了一项MKC-1的开放标签II期研究。入选标准包括不可切除或转移性胰腺癌，体能状态为1或更好，以及至少一种既往化疗方案失败。MKC-1口服给药，每日两次，初始剂量为100 mg/m2，连续给药14天，28天为一个周期。在试验期间，将该方案修改为每天150 mg的固定和连续给药。初始目标33例患者中有20例入选，中位年龄为61岁（范围44 - 81岁）。未观察到客观缓解，1例患者显示病情稳定。从MKC-1给药开始，总生存期为101天，中位进展时间为42天。与MKC-1给药相关或可能相关的最常见不良事件为血液学毒性和疲乏。1例患者发生5级（致死性）全血细胞减少症。3级和4级事件包括血细胞减少症（淋巴细胞减少症、贫血）、高胆红素血症、肺炎、粘膜炎、疲乏、输注反应、厌食和低白蛋白血症。MKC-1给药与实质性毒性相关，在晚期胰腺癌患者中未显示出足够的活性，无法证明在该患者人群中进行进一步探索的合理性。
MKC-1 is an orally available cell cycle inhibitor with downstream targets that include tubulin and the importin-β family. We conducted an open-label Phase II study with MKC-1 in patients with advanced pancreatic cancer. Eligibility criteria included unresectable or metastatic pancreatic cancer, performance status of 1 or better, and failure of at least one prior regimen of chemotherapy. MKC-1 was administered orally, twice daily, initially at 100mg/m2 dosing for 14 consecutive days of a 28-day cycle. This schedule was modified during the trial to fixed and continuous dosing of 150mg per day. 20 of an original target of 33 patients were accrued, with a median age of 61 (range 44 to 81). No objective responses were observed, with one patient demonstrating stable disease. Overall survival was 101 days from the start of MKC-1 administration, and median time to progression was 42 days. The most common adverse events listed as related or possibly related to MKC-1 administration were hematologic toxicities and fatigue. One patient developed grade 5 (fatal) pancytopenia. Grade 3 and 4 events included cytopenias (lymphopenia, anemia), hyperbilirubinemia, pneumonia, mucositis, fatigue, infusion reaction, anorexia, and hypoalbuminemia. MKC-1 administration was associated with substantial toxicity and did not demonstrate sufficient activity in patients with advanced pancreatic cancer to justify further exploration in this patient population.
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影响因子：
6.2
作者：
Colucci, G;Giuliani, F;Lopez, M
通讯作者：
Lopez, M
影响因子：
8.8
作者：
Bramhall, SR;Schulz, J;Nemunaitis, J;Brown, PD;Baillet, M;Buckels, JAC
通讯作者：
Buckels, JAC
影响因子：
45.3
作者：
Van Cutsem, E;de Velde, HV;Von Hoff, D
通讯作者：
Von Hoff, D
影响因子：
45.3
作者：
Burris, HA;Moore, MJ;VanHoff, DD
通讯作者：
VanHoff, DD
影响因子：
158.5
作者：
Conroy, Thierry;Desseigne, Francoise;Ducreux, Michel
通讯作者：
Ducreux, Michel