S0356：一项 II 期临床和前瞻性分子试验，奥沙利铂、氟尿嘧啶和外照射放疗联合术前治疗食管腺癌患者。
S0356: a phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma.
机构信息
Gastrointestinal Malignancies, Desert Regional Medical Center Comprehensive Cancer Center, and Aptium Oncology, 1180 N Indian Canyon Dr, Palm Springs, CA 92262;
出版信息
J Clin Oncol. 2011 Dec 1;29(34):4555-60. doi: 10.1200/JCO.2011.36.7490. Epub 2011 Oct 24.
PURPOSE
Pathologic complete response (pCR) after neoadjuvant therapy for locally advanced esophageal adenocarcinoma is associated with improved survival. The Southwest Oncology Group designed a trimodality, phase II, single-arm trial with objectives of achieving a pCR rate of 40% with prospective exploratory analyses of intratumoral molecular markers postulated to affect response and survival.
PATIENTS AND METHODS
Patients with clinically staged II or III esophageal adenocarcinoma received oxaliplatin 85 mg/m(2) on days 1, 15, and 29; protracted-infusion fluorouracil (PI-FU) 180 mg/m(2)/d on days 8 through 43; and external-beam radiation therapy (EBRT) 5 days a week at 1.8 Gy/d for 25 fractions; surgery was performed 28 to 42 days after neoadjuvant therapy. Chemotherapy was planned after surgery. Tumors were analyzed for mRNA expression and polymorphisms in genes involved in drug metabolism and DNA repair.
RESULTS
Ninety-three patients were evaluable. Two deaths (2.2%) were attributable to preoperative therapy, and two deaths (2.2%) were attributable to surgery. Grade 3 and 4 toxicities were recorded for 47.3% and 19.4% of patients, respectively. Seventy-nine patients (84.9%) underwent surgery; 67.7% of patients had R0 resections. Twenty-six patients (28.0%) had confirmed pCR (95% CI, 19.1% to 38.2%). At a median follow-up of 39.2 months, estimates of median and 3-year overall survival (OS) were 28.3 months and 45.1%, respectively. Intratumoral ERCC-1 gene expression was inversely related to progression-free survival and OS.
CONCLUSION
Neoadjuvant oxaliplatin, PI-FU, and EBRT for esophageal adenocarcinoma is active and tolerable. Because the regimen failed to meet the primary end point, it does not define a new standard. However, future trials can be built on this platform to validate the role of ERCC-1 in determining the best systemic regimen for individual patients.
目的
新辅助治疗局部晚期食管腺癌后获得病理完全缓解（pCR）与生存改善相关。西南肿瘤协作组设计了一项三联疗法、Ⅱ期、单臂试验，目的是实现 40%的 pCR 率，并对假定影响反应和生存的肿瘤内分子标志物进行前瞻性探索性分析。
患者和方法
临床分期为Ⅱ或Ⅲ期食管腺癌患者接受奥沙利铂 85mg/m²，第 1、15 和 29 天；持续输注氟尿嘧啶（PI-FU）180mg/m²/天，第 8 至 43 天；外照射放疗（EBRT）每周 5 天，每天 1.8Gy，共 25 个分次；新辅助治疗后 28 至 42 天进行手术。手术后计划进行化疗。分析肿瘤的 mRNA 表达和参与药物代谢和 DNA 修复的基因的多态性。
结果
93 例患者可评估。2 例（2.2%）死亡与术前治疗有关，2 例（2.2%）死亡与手术有关。分别有 47.3%和 19.4%的患者发生 3 级和 4 级毒性。79 例（84.9%）患者接受手术；67.7%的患者行 R0 切除。26 例（28.0%）患者确认 pCR（95%CI，19.1%至 38.2%）。中位随访 39.2 个月时，中位和 3 年总生存（OS）估计值分别为 28.3 个月和 45.1%。肿瘤内 ERCC-1 基因表达与无进展生存和 OS 呈负相关。
结论
奥沙利铂、PI-FU 和 EBRT 新辅助治疗食管腺癌具有活性且可耐受。由于该方案未能达到主要终点，因此它并未定义新的标准。然而，未来的试验可以在此平台上进行，以验证 ERCC-1 在确定最佳全身治疗方案方面对个体患者的作用。
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