Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer Pub Date : 2024-09-01 DOI:10.1016/j.clcc.2024.03.003

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引用次数: 0

Abstract

Background

Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy—TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW.

Methods

This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)—TNT-arm—or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR).

Results

Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns).

Conclusions

TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

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巴西-TNT：新辅助化疗后 FOLFIRINOX 与化疗治疗 II/III 期直肠癌的随机 2 期试验

背景新辅助放疗和以奥沙利铂为基础的全身治疗（全新辅助治疗-TNT）已被证明可提高局部直肠癌的反应率和器官保留率。然而，有关治疗方案的试验各不相同，很少有试验对完全应答者采用观察和等待（WW）方法。本试验评估了传统的长期化疗后巩固FOLFIRINOX是否能提高完全反应率，以及采用观察-等待（WW）方法治疗的患者人数。这是一项在巴西两家癌症中心进行的实用随机II期试验，纳入了T3+或N+直肠腺癌患者。患者在完成卡培他滨长疗程54 Gy化放疗后，按1:1随机分配到4个周期的mFOLFIRINOX（奥沙利铂85、伊立替康150、5-FU 2400）- TNT-治疗组或对照组，后者不包括进一步的新辅助治疗。所有患者均在放射治疗结束 12 周后接受专门的盆腔磁共振成像和乙状结肠镜检查，重新分期。临床完全反应患者采用WW方案进行随访。主要终点是完全反应：临床完全反应（cCR）或病理反应（pCR）。结果在2021年4月至2023年6月期间，55名患者随机接受了TNT治疗，53名患者接受了对照组治疗。74%的肿瘤为3期，距离肛门边缘的中位距离为6厘米，63%的肿瘤周缘有风险，33%的肿瘤累及括约肌。TNT 的 cCR + pCR 率为（31%），而对照组为（17%）（几率比 2.19，CI 95% 0.8-6.22 P = .091），WW 率分别为 16% 和 9%（P = ns）。中位随访时间为 8.1 个月，TNT 和对照组的复发率分别为 16% 和 21% (P = ns)。该试验得到了巴西政府的资助（PROADI-SUS - NUP 25000.164382/2020-81）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical colorectal cancer 医学-肿瘤学

CiteScore

5.50

自引率

2.90%

发文量

审稿时长

27 days

期刊介绍： Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.