A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study.
A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study.
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DOI：
10.1007/s10637-012-9916-5
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发表时间：
2013-08
影响因子：
3.4
通讯作者：
Lubner, Sam J.
中科院分区：
文献类型：
--
作者：
LoConte, Noelle K.;Holen, Kyle D.;Schelman, William R.;Mulkerin, Daniel L.;Deming, Dustin A.;Hernan, Hilary R.;Traynor, Anne M.;Goggins, Timothy;Groteluschen, David;Oettel, Kurt;Robinson, Emily;Lubner, Sam J.
化疗对胰腺癌和胆道癌的临床疗效甚微。高剂量、短疗程卡培他滨与奥沙利铂联合使用，已显示出一定的疗效，且掌跖红肿的发生率较低。通过缩短卡培他滨的使用时间，可以避免皮肤毒性，从而实现靶向药物索拉非尼的高暴露。所有患者均患有胰腺或胆道癌。两个队列的患者均接受奥沙利铂85 mg/m2，随后卡培他滨2250 mg/m2 PO，每8小时× 6次，从28天周期的第1天和第15天开始，或2DOC（2天奥沙利铂/卡培他滨）。队列1使用索拉非尼200mg BID，队列2使用索拉非尼400mg BID。16名患者入组。在所有周期中，最常见的1级或2级不良事件是疲劳（10分）、腹泻（10分）、恶心（9分）、呕吐（8分）、感觉神经病变（8分）、血小板减少（7分）、中性粒细胞减少（5分）和手足综合征（5分）。3级毒性包括中性粒细胞减少、粘膜炎、疲劳、呕吐和腹泻。队列1代表MTD。观察到两种部分反应，分别发生在胰腺癌和胆道癌中。索拉非尼联合2DOC的推荐II期剂量为BID 200mg。有罕见的3级毒性，最明显的是索拉非尼400mg BID。
Chemotherapy has yielded minimal clinical benefit in pancreatic and biliary tract cancer. A high-dose, short course capecitabine schedule with oxaliplatin, has shown some efficacy with a lower incidence of palmar-plantar erythrodysesthesia. Achieving high exposures of the targeted agent sorafenib may be possible with this shorter schedule of capecitabine by avoiding dermatologic toxicity. All patients had pancreatic or biliary tract cancer. Patients in both cohorts received oxaliplatin 85 mg/m2 followed by capecitabine 2250 mg/m2 PO every 8 hours × 6 doses starting on days 1 and 15 of a 28 day cycle, or 2DOC (2 Day Oxaliplatin/Capecitabine). Cohort 1 used sorafenib 200 mg BID, and cohort 2 used sorafenib 400 mg BID. Sixteen patients were enrolled. Across all cycles the most common grade 1 or 2 adverse events were fatigue (10 pts), diarrhea (10 pts), nausea (9 pts), vomiting (8 pts), sensory neuropathy (8 pts), thrombocytopenia (7 pts), neutropenia (5 pts), and hand-foot syndrome (5 pts). Grade 3 toxicites included neutropenia, mucositis, fatigue, vomiting and diarrhea. Cohort 1 represented the MTD. Two partial responses were seen, one each in pancreatic and biliary tract cancers. The recommended phase II dose of sorafenib in combination with 2DOC is 200 mg BID. There were infrequent grade 3 toxicities, most evident with sorafenib at 400 mg BID.
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影响因子：
6.2
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通讯作者：
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