Takhar Harminder, Singhal Nimit, Mislang Anna, Kumar Raj, Kim Laurence, Selva-Nayagam Sid, Pittman Ken, Karapetis Chris, Borg Martin, Olver Ian N, Brown Michael P
Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Department of Medical Oncology, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia.
Asia Pac J Clin Oncol. 2018 Feb;14(1):91-100. doi: 10.1111/ajco.12749. Epub 2017 Aug 25.
Phase II study of celecoxib with docetaxel chemoradiotherapy (CRT) followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer.
Concurrent CRT has been associated with improvement in absolute 5-year survival by 10% and is the standard of care for inoperable stage III nonsmall cell lung cancer. Preclinical evidence suggests that cyclooxygenase-2 inhibition may increase the efficacy of CRT.
Patients were treated with CRT (weekly docetaxel at 30 mg/m over 6 weeks with concurrent external beam radiotherapy with 60 Gy in 30 fractions) followed by consolidation chemotherapy with docetaxel and cisplatin, each at 75 mg/m given 3 weekly for four cycles. Patients were to receive celecoxib 400 mg twice daily during treatment. Prophylactic cranial irradiation (30 Gy in 15 fractions) was offered if there was disease response.
Twenty-four patients commenced CRT. Nineteen patients commenced consolidation therapy with 14 patients completing treatment. Twelve patients had treatment with celecoxib. In the total cohort, the median overall survival (mOS) was 21 months and progression-free survival (PFS) was 16 months. Overall response rate was 59% and disease control rate was 82%. Three patient deaths occurred. Significant grade 3/4 toxicity included radiation pneumonitis (17%), febrile neutropenia (17%), infection/sepsis with or with neutropenia (25%) and esophagitis (12.5%). Retrospective analysis of celecoxib versus no celecoxib treatment showed favorable mOS 26.5 versus 17.5 months and PFS 22 versus 16 months, but this did not reach statistical significance.
The activity of this regimen has been demonstrated. Treatment-related toxicity was substantial. The role of celecoxib in addition to CRT could not be demonstrated in this study because of the small number of patients.
塞来昔布联合多西他赛同步放化疗（CRT），序贯多西他赛联合顺铂巩固化疗并联合塞来昔布维持治疗不可切除的Ⅲ期非小细胞肺癌的Ⅱ期研究
同步放化疗可使绝对5年生存率提高10%，是不可切除Ⅲ期非小细胞肺癌的标准治疗方案。临床前证据表明，环氧合酶-2抑制可能会提高放化疗疗效。
患者接受同步放化疗（每周30mg/m²多西他赛，共6周，同时进行60Gy分30次的体外照射放疗），随后进行多西他赛和顺铂的巩固化疗，各75mg/m²，每3周1次，共4个周期。患者在治疗期间每天服用2次400mg塞来昔布。若有疾病缓解则给予预防性颅脑照射（15次，共30Gy）。
24例患者开始同步放化疗。19例患者开始巩固治疗，其中14例完成治疗。12例患者接受了塞来昔布治疗。在整个队列中，中位总生存期（mOS）为21个月，无进展生存期（PFS）为16个月。总缓解率为59%，疾病控制率为82%。发生3例患者死亡。显著的3/4级毒性包括放射性肺炎（17%）、发热性中性粒细胞减少（17%）、伴有或不伴有中性粒细胞减少的感染/败血症（25%）和食管炎（12.5%）。对接受塞来昔布治疗与未接受塞来昔布治疗的患者进行回顾性分析显示，mOS分别为26.5个月和17.5个月，PFS分别为22个月和16个月，但未达到统计学显著性。
已证实该方案的活性。治疗相关毒性较大。由于患者数量较少，本研究未能证实塞来昔布在同步放化疗之外的作用。
