比较新辅助紫杉醇联合铂类与5-氟尿嘧啶联合铂类治疗食管或胃食管交界鳞状细胞癌的III期随机试验。

Phase III randomized trial comparing neoadjuvant paclitaxel plus platinum with 5-fluorouracil plus platinum in esophageal or gastroesophageal junction squamous cell carcinoma.

作者信息

Noronha Vanita, Patil Vijay Maruti, Menon Nandini, Joshi Amit, Shah Minit Jalan, Singh Ajaykumar, Goud Supriya, Shah Srushti, More Sucheta, Nawale Kavita, Nakti Dipti, Yadav Akanksha, Jogdhankar Shweta, Kaushal Rajiv Kumar, Tiwari Virendra Kumar, Niyogi Devayani, Purandare Nilendu, Janu Amit, Chakrabarty Nivedita, Mahajan Abhishek, Tibdewal Anil, Agarwal Jaiprakash, Pawar Akash, Chowdhury Oindrila Roy, Sharma Vibhor, Kapu Venkatesh, Trikha Mehak, Kumar Srigadha Vivek, Kolkur Manali, Bhagyavant Priyanka, Peelay Zoya, Khedkar Rutvij, Jain Medha, Badwe Rajendra Achyut, Prabhash Kumar

机构信息

Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India.

Department of Medical Oncology, PD Hinduja Hospital Medical Research Centre, Mumbai, Khar and Mahim, India.

出版信息

J Natl Cancer Inst. 2025 Jan 1;117(1):58-75. doi: 10.1093/jnci/djae214.

DOI:10.1093/jnci/djae214

PMID:39222012

Abstract

BACKGROUND

Standard neoadjuvant chemotherapy for locally advanced esophageal or gastroesophageal junction squamous cancer, 5-fluorouracil plus platinum, is toxic and logistically challenging; alternative regimens are needed.

METHODS

This was a phase III randomized open-label noninferiority trial at Tata Memorial Center, India, in resectable locally advanced esophageal or gastroesophageal junction squamous cancer. Patients were randomly assigned 1:1 to 3 cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin area under the curve 6) with paclitaxel 175 mg/m2 (day 1) or 5-fluorouracil 1000 mg/m2 continuous infusion (days 1-4), followed by surgery.

RESULTS

Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Statistically significantly more patients on paclitaxel plus platinum (n =194, 92.3%) received all 3 chemotherapy cycles than on 5-fluorouracil with platinum (n = 170, 85.9%; P = .009). 5-fluorouracil plus platinum caused more grade 3 or higher toxicities (n = 124, 69.7%) than paclitaxel plus platinum (n = 97, 51.9%; P = .001). Surgery was performed in 131 (62.4%) patients on 5-fluorouracil plus platinum vs 139 (66.2%) on paclitaxel plus platinum (P = .415). Paclitaxel plus platinum resulted in higher pathologic primary tumor clearance (n = 33, 25.8%, vs n = 17, 15%; P = .04) and pathologic complete responses in 21.9% compared with 12.4% from 5-fluorouracil plus platinum (P = .053). Median overall survival was 27.5 months (95% confidence interval [CI] = 18.6 to 43.5 months) from paclitaxel plus platinum, which was noninferior to 27.1 months (95% CI = 18.8 to 40.7 months) from 5-fluorouracil plus platinum (hazard ratio [HR] = 0.89, 95% CI = 0.72 to 1.09; P = .346).

CONCLUSION

Neoadjuvant paclitaxel plus platinum chemotherapy is safer and results in similar R0 resections, higher pathologic tumor clearance and noninferior survival compared with 5-fluorouracil plus platinum. Paclitaxel plus platinum should replace 5-fluorouracil plus platinum as neoadjuvant chemotherapy for resectable locally advanced esophagealor gastroesophageal junction squamous cancer.

CLINICAL TRIALS REGISTRY INDIA NUMBER

CTRI/2014/04/004516.

摘要

背景

对于局部晚期食管或食管胃交界部鳞状癌，标准的新辅助化疗方案是5-氟尿嘧啶联合铂类，该方案毒性大且在组织实施上具有挑战性，因此需要替代方案。

方法

这是一项在印度塔塔纪念中心进行的III期随机开放标签非劣效性试验，针对可切除的局部晚期食管或食管胃交界部鳞状癌患者。患者按1:1随机分组，接受3个周期、每3周一次的铂类（顺铂75mg/m²或卡铂曲线下面积6）联合紫杉醇175mg/m²（第1天）或5-氟尿嘧啶1000mg/m²持续输注（第1 - 4天），之后进行手术。

结果

2014年8月至2022年6月期间，我们共纳入420例患者，每组210例。接受紫杉醇联合铂类治疗的患者中，有194例（92.3%）完成了全部3个化疗周期，这在统计学上显著多于接受5-氟尿嘧啶联合铂类治疗的患者（170例，85.9%；P = 0.009）。5-氟尿嘧啶联合铂类导致的3级及以上毒性反应（124例，69.7%）多于紫杉醇联合铂类（97例，51.9%；P = 0.001）。接受5-氟尿嘧啶联合铂类治疗的患者中有131例（62.4%）进行了手术，而接受紫杉醇联合铂类治疗的患者中有139例（66.2%）进行了手术（P = 0.415）。紫杉醇联合铂类组的病理原发肿瘤清除率更高（33例，25.8%，对比5-氟尿嘧啶联合铂类组的17例，15%；P = 0.04），病理完全缓解率为21.9%，而5-氟尿嘧啶联合铂类组为12.4%（P = 0.053）。紫杉醇联合铂类组的中位总生存期为27.5个月（95%置信区间[CI] = 18.6至43.5个月），不劣于5-氟尿嘧啶联合铂类组的27.1个月（95%CI = 18.8至40.7个月）（风险比[HR] = 0.89，95%CI = 0.72至1.09；P = 0.346）。