{"title":"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","authors":"","doi":"10.1016/j.clcc.2024.03.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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<span>. 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.</span></p></div><div><h3>Methods</h3><p>This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma<span><span>. After completing a long-course 54 Gy chemoradiation<span><span><span> with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, </span>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 </span>pelvic magnetic resonance imaging and </span></span>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).</span></p></div><div><h3>Results</h3><p><span>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 </span><em>P</em> = .091) and rates of WW were 16% and 9% (<em>P</em> = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (<em>P</em> = ns).</p></div><div><h3>Conclusions</h3><p>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).</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 3","pages":"Pages 238-244"},"PeriodicalIF":3.3000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer\",\"authors\":\"\",\"doi\":\"10.1016/j.clcc.2024.03.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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<span>. 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.</span></p></div><div><h3>Methods</h3><p>This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma<span><span>. After completing a long-course 54 Gy chemoradiation<span><span><span> with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, </span>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 </span>pelvic magnetic resonance imaging and </span></span>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).</span></p></div><div><h3>Results</h3><p><span>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 </span><em>P</em> = .091) and rates of WW were 16% and 9% (<em>P</em> = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (<em>P</em> = ns).</p></div><div><h3>Conclusions</h3><p>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).</p></div>\",\"PeriodicalId\":10373,\"journal\":{\"name\":\"Clinical colorectal cancer\",\"volume\":\"23 3\",\"pages\":\"Pages 238-244\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical colorectal cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1533002824000264\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical colorectal cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1533002824000264","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer
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).
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.