Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.
Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.
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DOI：
10.1186/s12885-016-2485-9
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发表时间：
2016-07-13
期刊：
影响因子：
3.8
通讯作者：
Enzinger PC
中科院分区：
文献类型：
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作者：
Cleary JM;Mamon HJ;Szymonifka J;Bueno R;Choi N;Donahue DM;Fidias PM;Gaissert HA;Jaklitsch MT;Kulke MH;Lynch TP;Mentzer SJ;Meyerhardt JA;Swanson RS;Wain J;Fuchs CS;Enzinger PC
接受三联疗法治疗的局部晚期食道癌患者复发率较高。临床前证据表明，抑制环氧合酶2(COX2)可以增加放化疗的有效性，而在人类中的观察研究表明，抑制COX-2可能会降低食道癌的风险。这项试验测试了COX2抑制剂塞来昔布与新佐剂伊立替康/顺铂联合化疗的安全性和有效性。这项单臂2期试验将伊立替康、顺铂和塞来昔布与同期放射治疗相结合。IIA-IVA期食道癌患者每周接受顺铂30 mg/m2加伊立替康65 mg/m2，在第1、2、4、5周的同时接受5040 mg/m2的放射治疗。塞来昔布400 mg在放化疗期间每天口服两次，手术前最多1周，手术后6个月。40例患者入选，其中IIa期(30%)、IIb期(20%)、III期(22.5%)和IVa期(27.5%)食道或胃食道交界区癌(AJCC，第5版)。放化疗期间，与3-4级治疗相关的毒性包括吞咽困难(20%)、厌食(17.5%)、脱水(17.5%)、恶心(15%)、中性粒细胞减少(12.5%)、腹泻(10%)、疲劳(7.5%)和发热中性粒细胞减少(7.5%)。病理完全缓解率为32.5%。中位无进展生存期为15.7个月，中位总生存期为34.7个月。在这项研究中接受治疗的患者中有15%(n = 6)发生脑转移。在新辅助顺铂-伊立替康化疗中加入塞来昔布是可以耐受的；然而，总体存活率似乎与之前单独使用新辅助顺铂-伊立替康化疗的研究相当。在食道癌的新辅助放化疗中加入塞来昔布的进一步研究是没有根据的。ClinicalTrials.gov：NCT00137852,2005年8月29日注册。
Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m2 plus irinotecan 65 mg/m2 on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3–4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted. Clinicaltrials.gov: NCT00137852, registered August 29, 2005.