Phase I/II Trial of Preoperative Oxaliplatin, Docetaxel, and Capecitabine With Concurrent Radiation Therapy in Localized Carcinoma of the Esophagus or Gastroesophageal Junction
Phase I/II Trial of Preoperative Oxaliplatin, Docetaxel, and Capecitabine With Concurrent Radiation Therapy in Localized Carcinoma of the Esophagus or Gastroesophageal Junction
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DOI：
10.1200/jco.2009.24.8773
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发表时间：
2010-05-01
影响因子：
45.3
通讯作者：
Hainsworth, John D.
中科院分区：
文献类型：
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作者：
Spigel, David R.;Greco, F. Anthony;Hainsworth, John D.
目的术前放化疗是可切除食管癌的主要治疗方法。使用新药物的联合治疗方案可能会改善患者的预后。这个多中心的社区为基础的I/II期试验研究了一个现代的三联方案，包括奥沙利铂，多西他赛，卡培他滨（ODC）结合放射治疗（RT）。患者和MethodsThe主要终点是病理完全缓解（pCR）率。入选标准包括可切除的中/远端食管或胃食管交界处I至III期癌症、可测量的疾病和东部肿瘤协作组体能状态（ECOG PS）为0或1。治疗包括奥沙利铂40 mg/m2、多西他赛20 mg/m2（静脉注射，每周一次x5）;卡培他滨1,000 mg/m2，口服，每日两次，第1 - 7、15 - 21和29 - 35天;同时RT（45戈伊）。在第9至12周期间进行切除。ODC和RT的安全性，确定在I期部分（n = 10）之前阶段II.ResultsFifty-nine例患者入组（2005年9月至2008年2月; I期/队列1，10例患者; I期/队列2/II期，49例患者）。基线特征包括中位年龄63岁; 84%为男性; ECOG PS 0和1分别为51%和49%;腺癌和鳞状细胞分别为69%和18%; I、II和III期分别为12%、41%和45%。I期研究显示无剂量限制性毒性。缓解：pCR率为49%;客观缓解率为61%（24例完全缓解，6例部分缓解）;疾病稳定率为6%;疾病进展率为2%。69%的患者接受了手术。生存期：中位随访时间为116周;中位无病生存期（DFS）和总生存期（OS）分别为16.3和24.1个月。2年DFS和OS分别为45.1%和52.2%。最常见（>= 5%）的3 - 4级非血液学毒性为厌食（20%）、脱水（16%）、腹泻（8%）、吞咽困难（10%）、食管炎（20%）、疲乏（12%）、高血糖（6%）、恶心（16%）、肺部症状（14%）、败血症（6%）和呕吐（16%）。其他3 ~ 4级血液学和非血液学毒性均不常见（< 5%）。结论术前ODC加RT治疗局部食管癌是有效的，相对安全。重要的是，这种治疗可以在8周内进行。该方案需要在这种情况下进行额外的研究，并与新的生物制剂联合使用。
PurposePreoperative chemoradiotherapy is a primary treatment option for patients with resectable esophageal cancer. Combination regimens using newer agents may improve patient outcomes. This multicenter community-based phase I/II trial examined a modern triplet regimen comprised of oxaliplatin, docetaxel, and capecitabine (ODC) combined with radiation therapy (RT).Patients and MethodsThe primary end point was the pathologic complete response (pCR) rate. Eligibility criteria included resectable stage I to III cancer of the mid-/distal-esophagus or gastroesophageal junction, measurable disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Treatment included oxaliplatin 40 mg/m(2), docetaxel 20 mg/m(2) (intravenous, weekly x 5); capecitabine 1,000 mg/m(2) orally twice daily on days 1 to 7, 15 to 21, and 29 to 35; and concurrent RT (45 Gy). Resection was performed during weeks 9 to 12. ODC and RT safety was determined in a phase I portion (n = 10) preceding phase II.ResultsFifty-nine patients were enrolled (September 2005 to February 2008; phase I/cohort 1, 10 patients; phase I/cohort 2/phase II, 49 patients). Baseline characteristics included median age of 63 years; 84% male; ECOG PS 0 and 1, 51% and 49%, respectively; adenocarcinoma and squamous cell, 69% and 18%, respectively; stage I, II, and III, 12%, 41%, and 45%, respectively. Phase I revealed no dose-limiting toxicity. Responses: pCR rate, 49%; objective response rate, 61% (24 complete and six partial responses); stable disease, 6%; and progressive disease, 2%. Sixty-nine percent of patients underwent surgery. Survival: median follow-up, 116 weeks; median disease-free survival (DFS) and overall survival (OS) were 16.3 and 24.1 months, respectively. Two-year DFS and OS were 45.1% and 52.2%, respectively. Most common (>= 5%) grade 3 to 4 nonhematologic toxicities were anorexia (20%), dehydration (16%), diarrhea (8%), dysphagia (10%), esophagitis (20%), fatigue (12%), hyperglycemia (6%), nausea (16%), pulmonary symptoms (14%), sepsis (6%), and vomiting (16%). All other grade 3 to 4 hematologic and nonhematologic toxicities were uncommon (< 5%).ConclusionPreoperative ODC plus RT is active and relatively safe in patients with locoregional esophageal cancer. Importantly, this therapy can be administered within 8 weeks. This regimen warrants additional study in this setting and in combination with newer biologic agents.