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基于卡铂-紫杉醇的每周根治性放化疗治疗不适合铂类-氟嘧啶类治疗的食管癌患者的结果:一项多中心回顾性研究。

Outcome of Weekly Carboplatin-Paclitaxel-based Definitive Chemoradiation in Oesophageal Cancer in Patients Not Considered to be Suitable for Platinum-Fluoropyrimidine-based Treatment: A Multicentre, Retrospective Review.

机构信息

Oxford University Hospital NHS Foundation Trust, Oxford, UK.

Cardiff University, Centre for Trials Research, Cardiff, UK.

出版信息

Clin Oncol (R Coll Radiol). 2020 Feb;32(2):121-130. doi: 10.1016/j.clon.2019.09.058. Epub 2019 Oct 26.

Abstract

AIMS

Although cisplatin-fluoropyrimidine-based definitive chemoradiotherapy (dCRT) is a standard of care for oesophageal cancer, toxicity is significant and limits its use in elderly and frail patients. Weekly carboplatin-paclitaxel-based dCRT provides a viable alternative, although prospective data are lacking in the dCRT setting. Here we report the results of a national, multicentre retrospective review of outcome in patients treated with weekly carboplatin-paclitaxel-based dCRT.

MATERIALS AND METHODS

In this multicentre retrospective study of nine radiotherapy centres across the UK we evaluated the outcome of patients who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous cell or undifferentiated; World Health Organization performance status 0-2; stage I-III disease) and had been selected to receive weekly carboplatin-paclitaxel-based dCRT as they were considered not suitable for cisplatin-fluoropyrimidine-based dCRT. dCRT consisted of carboplatin AUC 2 and paclitaxel 50 mg/m (days 1, 8, 15, 22, 29) and the recommended radiation dose was 50 Gy in 25 daily fractions. We assessed overall survival, progression-free survival (PFS; overall, local and distant), proportion of patients who were failure free at the response assessment (12 weeks after dCRT), treatment compliance and toxicity.

RESULTS

In total, 214 patients from nine UK centres were treated between 15 February 2013 and 19 March 2019: 39.7% of patients were ≥75 years; 18.7% ≥ 80 years. Indications for weekly carboplatin-paclitaxel-based dCRT were comorbidities (47.2%), clinician choice (36.4%) and poor tolerance/progression on cisplatin-fluoropyrimidine induction chemotherapy (15.8%). The median overall survival was 24.28 months (95% confidence interval 20.07-30.09) and the median PFS was 16.33 months (95% confidence interval 14.29-20.96). Following treatment, 69.1% (96/139) had a combined complete response on endoscopy with non-progression (complete response/partial response/stable disease) on imaging. The 1- and 2-year overall survival rates for this patient group were 81.9% (95% confidence interval 75.6-86.8%) and 50.6% (95% confidence interval 40.5-60.0%), respectively. Thirty-three per cent (n = 70) of patients experienced at least one grade 3 + acute toxicity (grade 3/4 haematological: 10%; grade 3/4 non-haematological: 32%) and there were no treatment-related deaths. 86.9% of patients completed at least four cycles of concomitant weekly carboplatin-paclitaxel-based chemotherapy and planned radiotherapy was completed in 97.7% (209/214).

CONCLUSION

Weekly carboplatin-paclitaxel-based CRT seems to be well tolerated in elderly patients and in those with comorbidities, where cisplatin-fluoropyrimidine-based dCRT is contraindicated. Survival outcomes are comparable with cisplatin-fluoropyrimidine-based dCRT.

摘要

目的

虽然顺铂-氟嘧啶为基础的放化疗(dCRT)是食管癌的标准治疗方法,但毒性显著,限制了其在老年和体弱患者中的应用。每周卡铂-紫杉醇为基础的 dCRT 提供了一种可行的替代方案,尽管在 dCRT 环境中缺乏前瞻性数据。在这里,我们报告了英国九家放疗中心进行的每周卡铂-紫杉醇为基础的 dCRT 治疗患者的结果的全国性、多中心回顾性研究。

材料和方法

在这项针对英国九家放疗中心的多中心回顾性研究中,我们评估了患有非转移性、组织学证实的食管癌(腺癌、鳞状细胞癌或未分化癌;世界卫生组织表现状态 0-2;I-III 期疾病)并被选择接受每周卡铂-紫杉醇为基础的 dCRT 的患者的结果,因为他们被认为不适合顺铂-氟嘧啶为基础的 dCRT。dCRT 包括卡铂 AUC 2 和紫杉醇 50mg/m(第 1、8、15、22、29 天),推荐的放疗剂量为 50Gy,分 25 个每日剂量。我们评估了总生存率、无进展生存率(PFS;总体、局部和远处)、在 dCRT 后 12 周时无失败反应的患者比例(12 周时无失败反应)、治疗依从性和毒性。

结果

共有来自英国九家中心的 214 名患者在 2013 年 2 月 15 日至 2019 年 3 月 19 日期间接受治疗:39.7%的患者年龄≥75 岁;18.7%≥80 岁。每周卡铂-紫杉醇为基础的 dCRT 的适应症为合并症(47.2%)、临床医生选择(36.4%)和对顺铂-氟嘧啶诱导化疗的耐受性差/进展(15.8%)。中位总生存期为 24.28 个月(95%置信区间为 20.07-30.09),中位 PFS 为 16.33 个月(95%置信区间为 14.29-20.96)。治疗后,69.1%(96/139)的患者内镜检查有联合完全反应,影像学检查无进展(完全缓解/部分缓解/稳定疾病)。该患者组的 1 年和 2 年总生存率分别为 81.9%(95%置信区间为 75.6-86.8%)和 50.6%(95%置信区间为 40.5-60.0%)。33%(n=70)的患者至少出现一次 3 级及以上急性毒性(3/4 级血液学毒性:10%;3/4 级非血液学毒性:32%),无治疗相关死亡。86.9%的患者至少完成了四个周期的同步每周卡铂-紫杉醇化疗,97.7%(209/214)的计划放疗完成。

结论

每周卡铂-紫杉醇为基础的 CRT 在老年患者和有合并症的患者中耐受性良好,这些患者对顺铂-氟嘧啶为基础的 dCRT 是禁忌的。生存结果与顺铂-氟嘧啶为基础的 dCRT 相当。

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