Department of Medical Oncology, Princess Margaret and Toronto General Hospitals of the University Health Network, Toronto, Ontario, Canada.
Cancer. 2010 Sep 1;116(17):4023-32. doi: 10.1002/cncr.25349.
Esophagectomy for locally advanced esophageal cancer (LAEC) is associated with limited survival. Trimodality therapy yields a small survival advantage, with cisplatin and 5-fluorouracil regimens most frequently studied. Newer regimens may impact these poor outcomes. This phase 2 trial assessed the feasibility and efficacy of induction chemoradiotherapy with cisplatin and irinotecan followed by esophagectomy.
Patients with LAEC of the thoracic esophagus or gastroesophageal junction underwent chemotherapy with preoperative irinotecan (65 mg/m(2)) plus cisplatin (30 mg/m(2)) on Weeks 1, 2, 4, 5, 7, and 8 with concurrent conformal radiotherapy (40 grays [Gy]/20 fractions during Weeks 4-7) and external beam boost (10 Gy/5 fractions at Week 8). Esophagectomy was performed between Weeks 12 and 16. Pathologic response was the primary endpoint with follow-up data on progression, survival, and toxicity as secondary endpoints.
Fifty-two patients were enrolled from November 2002 to October 2005. Nineteen patients had American Joint Committee on Cancer stage II, 22 had stage III, and 11 had stage IVA disease. Grade 3 to 4 toxicity (graded according to the National Cancer Institute Common Toxicity Criteria 2.0) during induction included neutropenia (36%), febrile neutropenia (8%), diarrhea (10%), and esophagitis (4%). Three patients withdrew from treatment due to toxicity. There was 1 treatment-related death. Clinical responses included complete response in 2%, partial response in 30%, stable disease in 62%, and progressive disease in 6% of patients. Dysphagia improved/resolved in 72% of patients during induction. Forty-three patients underwent esophagectomy and 7 (16%) achieved pathologic complete responses. Median and 3-year overall survival for patients receiving trimodality therapy was 36 months and 51%, respectively.
In LAEC, concurrent irinotecan/cisplatin and radiotherapy followed by esophagectomy is reported to be associated with dysphagia improvement in 72% of patients, a significant but manageable toxicity profile, and encouraging survival compared with historic controls.
局部晚期食管癌（LAEC）的食管切除术的生存率有限。三联疗法可带来较小的生存优势，其中顺铂和 5-氟尿嘧啶方案最常被研究。新的方案可能会影响这些不良结果。这项 2 期试验评估了顺铂和伊立替康诱导化疗联合食管切除术的可行性和疗效。
胸段食管或胃食管交界处的 LAEC 患者接受术前伊立替康（65mg/m²）联合顺铂（30mg/m²）化疗，第 1、2、4、5、7 和 8 周，同时进行适形放疗（第 4-7 周 40 戈瑞[Gy]/20 次分割）和外部束增敏放疗（第 8 周 10Gy/5 次分割）。食管切除术在第 12-16 周进行。病理反应是主要终点，次要终点为进展、生存和毒性的随访数据。
2002 年 11 月至 2005 年 10 月期间共招募了 52 名患者。19 名患者为美国癌症联合委员会（AJCC）分期 II 期，22 名患者为 III 期，11 名患者为 IVA 期。诱导期间出现 3 级至 4 级毒性（根据国家癌症研究所通用毒性标准 2.0 分级），包括中性粒细胞减少症（36%）、发热性中性粒细胞减少症（8%）、腹泻（10%）和食管炎（4%）。有 3 名患者因毒性而退出治疗。有 1 例与治疗相关的死亡。临床反应包括完全缓解 2%，部分缓解 30%，稳定疾病 62%，进展疾病 6%。诱导期间 72%的患者吞咽困难得到改善/缓解。43 名患者接受了食管切除术，其中 7 名（16%）患者获得了病理完全缓解。接受三联疗法的患者的中位和 3 年总生存率分别为 36 个月和 51%。
在 LAEC 中，顺铂/伊立替康联合放疗联合食管切除术与 72%的患者吞咽困难改善相关，与历史对照相比，毒性谱具有显著但可管理的特征，且生存结果令人鼓舞。
