Phase III randomized trial comparing neoadjuvant paclitaxel+platinum to 5-fluorouracil+platinum in esophageal/GEJ squamous cell carcinoma.

IF 9.9 1区医学 Q1 ONCOLOGY JNCI Journal of the National Cancer Institute Pub Date : 2024-09-02 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, Rajeev Kumar, 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 Trika, Srigadha Vivek Kumar, Manali Kolkur, Priyanka Bhagyavant, Zoya Peelay, Rutvij Khedkar, Medha Jain, Rajendra Badwe, Kumar Prabhash

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Abstract

Purpose: Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed.

Patients and methods: Phase III randomized open-label non-inferiority trial at Tata Memorial Center, India, in resectable LAEGSC. Patients were randomized 1:1 to three cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin AUC 6) with paclitaxel 175 mg/m2 (day 1) or 5FU 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. Significantly more patients on paclitaxel + platinum (194 (92.3%)] received all 3 chemotherapy cycles than on 5FU+platinum (170 [85.9%]), P = .009. 5FU + platinum caused more grade ≥ 3 toxicities (124 [69.7%]) than paclitaxel + platinum (97 [51.9%]), P = .001. Surgery was performed in 131 (62.4%) patients on 5FU + platinum vs 139 (66.2%) on paclitaxel + platinum, P = .415. Paclitaxel + platinum resulted in higher pathologic primary tumor clearance (33 [25.8%]) vs 17 [15%]; P = .04), and pathologic complete responses in 21.9% compared to 12.4% from 5FU + platinum, P = .053. Median OS was 27.5 months (95% CI, 18.6-43.5) from paclitaxel + platinum, which was non-inferior to 27.1 months (95% CI, 18.8-40.7) from 5FU + platinum; HR, 0.89 (95% CI, 0.72-1.09); P = .346.

Conclusion: Neoadjuvant paclitaxel + platinum chemotherapy is safer, and results in similar R0 resections, higher pathologic tumor clearance and non-inferior survival, compared to 5FU + platinum. Paclitaxel + platinum should replace 5FU + platinum as NACT for resectable LAEGSC.

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.