First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer.
First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer.
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DOI：
10.1007/s00280-013-2359-7
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发表时间：
2014-02
影响因子：
3
通讯作者：
Cheng, Yung-Chi
中科院分区：
文献类型：
--
作者：
Saif, Muhammad Wasif;Li, Jia;Lamb, Lynne;Kaley, Kristin;Elligers, Kyle;Jiang, Zaoli;Bussom, Scott;Liu, Shwu-Huey;Cheng, Yung-Chi
临床前研究表明，中国植物配方PHY 906与卡培他滨具有协同抗肿瘤活性。我们的I期研究确定了卡培他滨1500 mg/m2 BID第1-7天和PHY 906 800 mg BID第1-4天每两周的最大耐受剂量。我们进行了这项II期研究，以探讨卡培他滨和PHY 906在既往接受过吉西他滨方案治疗的晚期胰腺癌患者中的疗效。患有胰腺癌且ECOG体力状态为0至2的患者接受PHY 906和卡培他滨。根据NCI-CTCAE v3.0评估毒性，根据RECIST q 6 wks评估缓解。使用流式细胞仪微球阵列检测细胞因子、趋化因子和生长因子的相关研究。采用埃德蒙顿症状自评量表评定患者的生活质量。主要目标是总生存期。该研究招募了25名患者。中位无进展生存期（mPFS）为10.1周（范围：0.4-54.1），中位总生存期（mOS）为21.6周（范围：0.4-84.1）。18例患者接受了至少2个周期的治疗，mPFS为12.3周，mOS为28周。6个月生存率为44%（11/25）。通过细胞因子谱将生存期缩短的患者分组在一起的无监督聚类显示，短期和长期存活者之间仅IL-6具有显著差异（p<0.001）。卡培他滨联合PHY 906是吉西他滨治疗APC失败后安全可行的挽救治疗方法。IL-6在肿瘤进展和肿瘤恶病质中的作用需要就其与胰腺癌的病理生理学和抗IL-6疗法的发展的关系进行研究。
Preclinical studies showed a Chinese botanical formula, PHY906, has synergistic anti-tumor activity with capecitabine. Our phase I study determined maximal tolerated dose of capecitabine 1500mg/m2 BID day 1–7 and PHY906 800mg BID day 1–4 every two weeks. We conducted this phase II study to explore the efficacy of capecitabine and PHY906 in patients with advanced pancreatic cancer who were previously treated with gemcitabine-based regimens. Patients with pancreatic cancer and an ECOG performance status of 0 to 2 received PHY906 and capecitabine. Toxicity was assessed per NCI-CTCAE v3.0 and response per RECIST q 6 wks. Correlative studies of cytokines, chemokines and growth factors were tested using a cytometric bead array. Quality of life was assessed by utilizing Edmonton Symptom Assessment System. The primary objective was overall survival. The study enrolled 25 patients. Median progression-free survival (mPFS) was 10.1 weeks (range: 0.4–54.1) and median overall survival (mOS) was 21.6 weeks (range: 0.4–84.1). 18 patients received at least 2 cycles, achieved mPFS of 12.3 weeks and mOS of 28 weeks. Six-month survival rate was 44% (11/25). Unsupervised clustering of patients grouped those with shortened survival together by their cytokine profile showed that only IL-6 had a significant difference (p<.001) between short and long term survivors. Capecitabine plus PHY906 provides a safe and feasible salvage therapy after gemcitabine failure for APC. Role of IL-6 in tumor progression and tumor cachexia needs to be investigated with respect to its relation to pathophysiology of pancreatic cancer and development of anti-IL-6 therapeutics.
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影响因子：
45.3
作者：
Scheithauer, W;Kornek, GV;Depisch, D
通讯作者：
Depisch, D
影响因子：
8.6
作者：
Morgan, E;Varro, R;Gaur, A
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Gaur, A
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3.5
作者：
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Heinemann, Volker
影响因子：
45.3
作者：
Cunningham, David;Chau, Ian;Neoptolemos, John P.
通讯作者：
Neoptolemos, John P.
影响因子：
45.3
作者：
Cartwright, TH;Cohn, A;Schulz, JJ
通讯作者：
Schulz, JJ