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

IF 9.9 1区医学 Q1 ONCOLOGY JNCI Journal of the National Cancer Institute Pub Date : 2025-01-01 DOI:10.1093/jnci/djae214

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

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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.

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比较新辅助紫杉醇+铂与 5-氟尿嘧啶+铂治疗食管/胃食管鳞状细胞癌的 III 期随机试验。

目的：局部晚期食管癌/胃食管交界处鳞状癌（LAEGSC）的标准新辅助化疗（NACT），即5-氟尿嘧啶（5FU）+铂，具有毒性和后勤挑战性；需要替代方案：印度塔塔纪念中心对可切除LAEGSC进行的III期随机开放标签非劣效性试验。患者按1:1随机分配到三周期铂（顺铂75 mg/m2或卡铂AUC 6）联合紫杉醇175 mg/m2（第1天）或5FU 1000 mg/m2持续输注（第1-4天），然后进行手术：2014年8月至2022年6月，我们共招募了420名患者，每组210人。接受紫杉醇+铂金治疗的患者（194人（92.3%））比接受5FU+铂金治疗的患者（170人[85.9%]）显著多出3个化疗周期，P = .009。与紫杉醇+铂（97 [51.9%]）相比，5FU+铂引起的≥3级毒性反应（124 [69.7%]）更多，P = .001。131例（62.4%）接受5FU+铂治疗的患者与139例（66.2%）接受紫杉醇+铂治疗的患者进行了手术，P = .415。紫杉醇+铂的病理原发肿瘤清除率更高（33 [25.8%]) vs 17 [15%]；P = .04），病理完全应答率为21.9%，而5FU+铂为12.4%，P = .053。紫杉醇+铂的中位OS为27.5个月（95% CI，18.6-43.5），不劣于5FU+铂的27.1个月（95% CI，18.8-40.7）；HR，0.89（95% CI，0.72-1.09）；P = .346.结论：与5FU+铂相比，新辅助紫杉醇+铂化疗更安全，可获得相似的R0切除率、更高的病理肿瘤清除率和非劣效生存率。紫杉醇+铂应取代5FU+铂作为可切除LAEGSC的NACT：CTRI/2014/04/004516.

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来源期刊

JNCI Journal of the National Cancer Institute 医学-肿瘤学

CiteScore

17.00

自引率

2.90%

发文量

203

审稿时长

4-8 weeks

期刊介绍： The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.