Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial
Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety...
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| Veröffentlicht in: | The Lancet (British edition) 2024-07, Vol.404 (10447), p.55-66 |
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| creator | Kato, Ken Machida, Ryunosuke Ito, Yoshinori Daiko, Hiroyuki Ozawa, Soji Ogata, Takashi Hara, Hiroki Kojima, Takashi Abe, Tetsuya Bamba, Takeo Watanabe, Masaya Kawakubo, Hirofumi Shibuya, Yuichi Tsubosa, Yasuhiro Takegawa, Naoki Kajiwara, Takeshi Baba, Hideo Ueno, Masaki Takeuchi, Hiroya Nakamura, Kenichi Kitagawa, Yuko Komatsu, Yoshito Akiyama, Yuji Takahashi, Masanobu Amagai, Kenji Matsushita, Naoyuki Hara, Hiroki Sato, Hiroshi Kojima, Takashi Minashi, Keiko Matsubara, Hisahiro Kikuchi, Yuji Kato, Ken Narumiya, Kosuke Kitagawa, Yuko Kubota, Yutaro Watanabe, Masayuki Ueno, Masaki Ozawa, Soji Ogata, Takashi Bamba, Takeo Ichikawa, Hiroshi Watanabe, Masaya Tsubosa, Yasuhiro Takeuchi, Hiroya Abe, Tetsuya Koike, Masahiko Tsunoda, Shigeru Doki, Yuichiro Miyata, Hiroshi Hirano, Motohiro Ikeda, Hiroko Goto, Masahiro Minami, Hironobu Masuzawa, Toru Tsuda, Masahiro Okada, Morihito Mukai, Hidenori Kajiwara, Takeshi Shibuya, Yuichi Morita, Masaru Baba, Eishi Baba, Hideo Inomata, Masafumi Sasaki, Ken |
| description | Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC.
In this randomised, open-label, phase 3 trial, patients aged 20–75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1–5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1–5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1–4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete.
A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8–70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4–77·8] vs 62·6% [55·5–68·9]; hazard ratio [HR] 0·68, 95% CI 0·50–0·92; p=0·006) but not in the N |
| doi_str_mv | 10.1016/S0140-6736(24)00745-1 |
| format | Article |
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In this randomised, open-label, phase 3 trial, patients aged 20–75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1–5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1–5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1–4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete.
A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8–70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4–77·8] vs 62·6% [55·5–68·9]; hazard ratio [HR] 0·68, 95% CI 0·50–0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3–74·3]; HR 0·84, 0·63–1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group.
Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy.
Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.</description><identifier>ISSN: 0140-6736</identifier><identifier>ISSN: 1474-547X</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(24)00745-1</identifier><identifier>PMID: 38876133</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>5-Fluorouracil ; Anastomotic leak ; Cancer ; Cancer therapies ; Chemotherapy ; Cisplatin ; Clinical trials ; Effectiveness ; Esophageal cancer ; Esophageal carcinoma ; Fatalities ; Gastrointestinal cancer ; Health services ; Labels ; Lymph nodes ; Lymphatic system ; Medical prognosis ; Medical research ; Metastasis ; Neutropenia ; Nutritional status ; Oncology ; Ostomy ; Paralysis ; Patients ; R&D ; Radiation therapy ; Randomization ; Research & development ; Squamous cell carcinoma ; Statistical analysis ; Surgery ; Surgical anastomosis ; Survival</subject><ispartof>The Lancet (British edition), 2024-07, Vol.404 (10447), p.55-66</ispartof><rights>2024 Elsevier Ltd</rights><rights>Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.</rights><rights>2024. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c323t-11963027add5eb404ac1eed2cde38069561eed4e80e06ab337d0f5cd852c20ee3</citedby><cites>FETCH-LOGICAL-c323t-11963027add5eb404ac1eed2cde38069561eed4e80e06ab337d0f5cd852c20ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/3075883324?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38876133$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kato, Ken</creatorcontrib><creatorcontrib>Machida, Ryunosuke</creatorcontrib><creatorcontrib>Ito, Yoshinori</creatorcontrib><creatorcontrib>Daiko, Hiroyuki</creatorcontrib><creatorcontrib>Ozawa, Soji</creatorcontrib><creatorcontrib>Ogata, Takashi</creatorcontrib><creatorcontrib>Hara, Hiroki</creatorcontrib><creatorcontrib>Kojima, Takashi</creatorcontrib><creatorcontrib>Abe, Tetsuya</creatorcontrib><creatorcontrib>Bamba, Takeo</creatorcontrib><creatorcontrib>Watanabe, Masaya</creatorcontrib><creatorcontrib>Kawakubo, Hirofumi</creatorcontrib><creatorcontrib>Shibuya, Yuichi</creatorcontrib><creatorcontrib>Tsubosa, Yasuhiro</creatorcontrib><creatorcontrib>Takegawa, Naoki</creatorcontrib><creatorcontrib>Kajiwara, Takeshi</creatorcontrib><creatorcontrib>Baba, Hideo</creatorcontrib><creatorcontrib>Ueno, Masaki</creatorcontrib><creatorcontrib>Takeuchi, Hiroya</creatorcontrib><creatorcontrib>Nakamura, Kenichi</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><creatorcontrib>Komatsu, Yoshito</creatorcontrib><creatorcontrib>Akiyama, Yuji</creatorcontrib><creatorcontrib>Takahashi, Masanobu</creatorcontrib><creatorcontrib>Amagai, Kenji</creatorcontrib><creatorcontrib>Matsushita, Naoyuki</creatorcontrib><creatorcontrib>Hara, Hiroki</creatorcontrib><creatorcontrib>Sato, Hiroshi</creatorcontrib><creatorcontrib>Kojima, Takashi</creatorcontrib><creatorcontrib>Minashi, Keiko</creatorcontrib><creatorcontrib>Matsubara, Hisahiro</creatorcontrib><creatorcontrib>Kikuchi, Yuji</creatorcontrib><creatorcontrib>Kato, Ken</creatorcontrib><creatorcontrib>Narumiya, Kosuke</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><creatorcontrib>Kubota, Yutaro</creatorcontrib><creatorcontrib>Watanabe, Masayuki</creatorcontrib><creatorcontrib>Ueno, Masaki</creatorcontrib><creatorcontrib>Ozawa, Soji</creatorcontrib><creatorcontrib>Ogata, Takashi</creatorcontrib><creatorcontrib>Bamba, Takeo</creatorcontrib><creatorcontrib>Ichikawa, Hiroshi</creatorcontrib><creatorcontrib>Watanabe, Masaya</creatorcontrib><creatorcontrib>Tsubosa, Yasuhiro</creatorcontrib><creatorcontrib>Takeuchi, Hiroya</creatorcontrib><creatorcontrib>Abe, Tetsuya</creatorcontrib><creatorcontrib>Koike, Masahiko</creatorcontrib><creatorcontrib>Tsunoda, Shigeru</creatorcontrib><creatorcontrib>Doki, Yuichiro</creatorcontrib><creatorcontrib>Miyata, Hiroshi</creatorcontrib><creatorcontrib>Hirano, Motohiro</creatorcontrib><creatorcontrib>Ikeda, Hiroko</creatorcontrib><creatorcontrib>Goto, Masahiro</creatorcontrib><creatorcontrib>Minami, Hironobu</creatorcontrib><creatorcontrib>Masuzawa, Toru</creatorcontrib><creatorcontrib>Tsuda, Masahiro</creatorcontrib><creatorcontrib>Okada, Morihito</creatorcontrib><creatorcontrib>Mukai, Hidenori</creatorcontrib><creatorcontrib>Kajiwara, Takeshi</creatorcontrib><creatorcontrib>Shibuya, Yuichi</creatorcontrib><creatorcontrib>Morita, Masaru</creatorcontrib><creatorcontrib>Baba, Eishi</creatorcontrib><creatorcontrib>Baba, Hideo</creatorcontrib><creatorcontrib>Inomata, Masafumi</creatorcontrib><creatorcontrib>Sasaki, Ken</creatorcontrib><creatorcontrib>JCOG1109 investigators</creatorcontrib><title>Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC.
In this randomised, open-label, phase 3 trial, patients aged 20–75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1–5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1–5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1–4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete.
A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8–70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4–77·8] vs 62·6% [55·5–68·9]; hazard ratio [HR] 0·68, 95% CI 0·50–0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3–74·3]; HR 0·84, 0·63–1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group.
Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy.
Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.</description><subject>5-Fluorouracil</subject><subject>Anastomotic leak</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Clinical trials</subject><subject>Effectiveness</subject><subject>Esophageal cancer</subject><subject>Esophageal carcinoma</subject><subject>Fatalities</subject><subject>Gastrointestinal cancer</subject><subject>Health services</subject><subject>Labels</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>Neutropenia</subject><subject>Nutritional status</subject><subject>Oncology</subject><subject>Ostomy</subject><subject>Paralysis</subject><subject>Patients</subject><subject>R&D</subject><subject>Radiation therapy</subject><subject>Randomization</subject><subject>Research & development</subject><subject>Squamous cell carcinoma</subject><subject>Statistical analysis</subject><subject>Surgery</subject><subject>Surgical anastomosis</subject><subject>Survival</subject><issn>0140-6736</issn><issn>1474-547X</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFks1u1DAQxy0EokvhEUCWuGylTbHjj2R7QWhpS1FFDxSJm-XYs2xWThxsp9D35UHqdMseAImTxzO_-c_YMwi9pOSYEirffCaUk0JWTM5LfkRIxUVBH6EZ5RUvBK--PkazPXKAnsW4JYRwScRTdMDqupKUsRn69d6PjYOEzQY6nzYQ9HC7wCm0w99eH7D9B46N75q2B4t_tGmDg7btPqQj7sFrux1vdJ-yLujUQbbWWcx5o53LkM1Bk_M9RD9s9DfQDpvJFfD84-rqnFKyxJ9Of14fnWCdC_TWd20Eu8il-xS8c5PtB-gLpxtwC5xVImA2PUS75-jJWrsILx7OQ_Tl7PR69aG4vDq_WL27LAwrWSooXUpGykpbK6DhhGtDAWxpLLCayKWQ05VDTYBI3TBWWbIWxtaiNCUBYIdovtMdgv8-Qkwqd2nAOZ3_YIyKEVlXQvCyyujrP9CtH0Ofu8tUJeqasZJnSuwoE3yMAdZqCG2nw62iRE1roO7XQE0zViVX92ugaM579aA-Nh3YfdbvuWfg7Q6A_B03LQQVTQvTDNoAJinr2_-UuAMK7MYC</recordid><startdate>20240706</startdate><enddate>20240706</enddate><creator>Kato, 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chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial</title><author>Kato, Ken ; Machida, Ryunosuke ; Ito, Yoshinori ; Daiko, Hiroyuki ; Ozawa, Soji ; Ogata, Takashi ; Hara, Hiroki ; Kojima, Takashi ; Abe, Tetsuya ; Bamba, Takeo ; Watanabe, Masaya ; Kawakubo, Hirofumi ; Shibuya, Yuichi ; Tsubosa, Yasuhiro ; Takegawa, Naoki ; Kajiwara, Takeshi ; Baba, Hideo ; Ueno, Masaki ; Takeuchi, Hiroya ; Nakamura, Kenichi ; Kitagawa, Yuko ; Komatsu, Yoshito ; Akiyama, Yuji ; Takahashi, Masanobu ; Amagai, Kenji ; Matsushita, Naoyuki ; Hara, Hiroki ; Sato, Hiroshi ; Kojima, Takashi ; Minashi, Keiko ; Matsubara, Hisahiro ; Kikuchi, Yuji ; Kato, Ken ; Narumiya, Kosuke ; Kitagawa, Yuko ; Kubota, Yutaro ; Watanabe, Masayuki ; Ueno, Masaki ; Ozawa, Soji ; Ogata, Takashi ; Bamba, Takeo ; Ichikawa, Hiroshi ; Watanabe, Masaya ; Tsubosa, Yasuhiro ; Takeuchi, Hiroya ; Abe, Tetsuya ; Koike, Masahiko ; Tsunoda, Shigeru ; Doki, Yuichiro ; Miyata, Hiroshi ; Hirano, Motohiro ; Ikeda, Hiroko ; Goto, Masahiro ; Minami, Hironobu ; Masuzawa, Toru ; Tsuda, Masahiro ; Okada, Morihito ; Mukai, Hidenori ; Kajiwara, Takeshi ; Shibuya, Yuichi ; Morita, Masaru ; Baba, Eishi ; Baba, Hideo ; Inomata, Masafumi ; Sasaki, Ken</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c323t-11963027add5eb404ac1eed2cde38069561eed4e80e06ab337d0f5cd852c20ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>5-Fluorouracil</topic><topic>Anastomotic leak</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Clinical trials</topic><topic>Effectiveness</topic><topic>Esophageal cancer</topic><topic>Esophageal carcinoma</topic><topic>Fatalities</topic><topic>Gastrointestinal cancer</topic><topic>Health services</topic><topic>Labels</topic><topic>Lymph nodes</topic><topic>Lymphatic system</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Metastasis</topic><topic>Neutropenia</topic><topic>Nutritional status</topic><topic>Oncology</topic><topic>Ostomy</topic><topic>Paralysis</topic><topic>Patients</topic><topic>R&D</topic><topic>Radiation therapy</topic><topic>Randomization</topic><topic>Research & development</topic><topic>Squamous cell carcinoma</topic><topic>Statistical analysis</topic><topic>Surgery</topic><topic>Surgical anastomosis</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kato, Ken</creatorcontrib><creatorcontrib>Machida, Ryunosuke</creatorcontrib><creatorcontrib>Ito, Yoshinori</creatorcontrib><creatorcontrib>Daiko, Hiroyuki</creatorcontrib><creatorcontrib>Ozawa, Soji</creatorcontrib><creatorcontrib>Ogata, Takashi</creatorcontrib><creatorcontrib>Hara, Hiroki</creatorcontrib><creatorcontrib>Kojima, Takashi</creatorcontrib><creatorcontrib>Abe, Tetsuya</creatorcontrib><creatorcontrib>Bamba, Takeo</creatorcontrib><creatorcontrib>Watanabe, Masaya</creatorcontrib><creatorcontrib>Kawakubo, Hirofumi</creatorcontrib><creatorcontrib>Shibuya, Yuichi</creatorcontrib><creatorcontrib>Tsubosa, Yasuhiro</creatorcontrib><creatorcontrib>Takegawa, Naoki</creatorcontrib><creatorcontrib>Kajiwara, Takeshi</creatorcontrib><creatorcontrib>Baba, Hideo</creatorcontrib><creatorcontrib>Ueno, Masaki</creatorcontrib><creatorcontrib>Takeuchi, Hiroya</creatorcontrib><creatorcontrib>Nakamura, Kenichi</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><creatorcontrib>Komatsu, Yoshito</creatorcontrib><creatorcontrib>Akiyama, Yuji</creatorcontrib><creatorcontrib>Takahashi, Masanobu</creatorcontrib><creatorcontrib>Amagai, Kenji</creatorcontrib><creatorcontrib>Matsushita, Naoyuki</creatorcontrib><creatorcontrib>Hara, Hiroki</creatorcontrib><creatorcontrib>Sato, Hiroshi</creatorcontrib><creatorcontrib>Kojima, Takashi</creatorcontrib><creatorcontrib>Minashi, Keiko</creatorcontrib><creatorcontrib>Matsubara, Hisahiro</creatorcontrib><creatorcontrib>Kikuchi, Yuji</creatorcontrib><creatorcontrib>Kato, Ken</creatorcontrib><creatorcontrib>Narumiya, Kosuke</creatorcontrib><creatorcontrib>Kitagawa, Yuko</creatorcontrib><creatorcontrib>Kubota, Yutaro</creatorcontrib><creatorcontrib>Watanabe, Masayuki</creatorcontrib><creatorcontrib>Ueno, Masaki</creatorcontrib><creatorcontrib>Ozawa, Soji</creatorcontrib><creatorcontrib>Ogata, Takashi</creatorcontrib><creatorcontrib>Bamba, Takeo</creatorcontrib><creatorcontrib>Ichikawa, Hiroshi</creatorcontrib><creatorcontrib>Watanabe, Masaya</creatorcontrib><creatorcontrib>Tsubosa, Yasuhiro</creatorcontrib><creatorcontrib>Takeuchi, Hiroya</creatorcontrib><creatorcontrib>Abe, Tetsuya</creatorcontrib><creatorcontrib>Koike, Masahiko</creatorcontrib><creatorcontrib>Tsunoda, 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Ryunosuke</au><au>Ito, Yoshinori</au><au>Daiko, Hiroyuki</au><au>Ozawa, Soji</au><au>Ogata, Takashi</au><au>Hara, Hiroki</au><au>Kojima, Takashi</au><au>Abe, Tetsuya</au><au>Bamba, Takeo</au><au>Watanabe, Masaya</au><au>Kawakubo, Hirofumi</au><au>Shibuya, Yuichi</au><au>Tsubosa, Yasuhiro</au><au>Takegawa, Naoki</au><au>Kajiwara, Takeshi</au><au>Baba, Hideo</au><au>Ueno, Masaki</au><au>Takeuchi, Hiroya</au><au>Nakamura, Kenichi</au><au>Kitagawa, Yuko</au><au>Komatsu, Yoshito</au><au>Akiyama, Yuji</au><au>Takahashi, Masanobu</au><au>Amagai, Kenji</au><au>Matsushita, Naoyuki</au><au>Hara, Hiroki</au><au>Sato, Hiroshi</au><au>Kojima, Takashi</au><au>Minashi, Keiko</au><au>Matsubara, Hisahiro</au><au>Kikuchi, Yuji</au><au>Kato, Ken</au><au>Narumiya, Kosuke</au><au>Kitagawa, Yuko</au><au>Kubota, Yutaro</au><au>Watanabe, Masayuki</au><au>Ueno, Masaki</au><au>Ozawa, Soji</au><au>Ogata, Takashi</au><au>Bamba, Takeo</au><au>Ichikawa, Hiroshi</au><au>Watanabe, Masaya</au><au>Tsubosa, Yasuhiro</au><au>Takeuchi, Hiroya</au><au>Abe, Tetsuya</au><au>Koike, Masahiko</au><au>Tsunoda, Shigeru</au><au>Doki, Yuichiro</au><au>Miyata, Hiroshi</au><au>Hirano, Motohiro</au><au>Ikeda, Hiroko</au><au>Goto, Masahiro</au><au>Minami, Hironobu</au><au>Masuzawa, Toru</au><au>Tsuda, Masahiro</au><au>Okada, Morihito</au><au>Mukai, Hidenori</au><au>Kajiwara, Takeshi</au><au>Shibuya, Yuichi</au><au>Morita, Masaru</au><au>Baba, Eishi</au><au>Baba, Hideo</au><au>Inomata, Masafumi</au><au>Sasaki, Ken</au><aucorp>JCOG1109 investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2024-07-06</date><risdate>2024</risdate><volume>404</volume><issue>10447</issue><spage>55</spage><epage>66</epage><pages>55-66</pages><issn>0140-6736</issn><issn>1474-547X</issn><eissn>1474-547X</eissn><abstract>Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC.
In this randomised, open-label, phase 3 trial, patients aged 20–75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1–5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1–5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1–4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete.
A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8–70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4–77·8] vs 62·6% [55·5–68·9]; hazard ratio [HR] 0·68, 95% CI 0·50–0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3–74·3]; HR 0·84, 0·63–1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group.
Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy.
Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>38876133</pmid><doi>10.1016/S0140-6736(24)00745-1</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2024-07, Vol.404 (10447), p.55-66 |
| issn | 0140-6736 1474-547X 1474-547X |
| language | eng |
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| source | Elsevier ScienceDirect Journals Complete; ProQuest Central UK/Ireland |
| subjects | 5-Fluorouracil Anastomotic leak Cancer Cancer therapies Chemotherapy Cisplatin Clinical trials Effectiveness Esophageal cancer Esophageal carcinoma Fatalities Gastrointestinal cancer Health services Labels Lymph nodes Lymphatic system Medical prognosis Medical research Metastasis Neutropenia Nutritional status Oncology Ostomy Paralysis Patients R&D Radiation therapy Randomization Research & development Squamous cell carcinoma Statistical analysis Surgery Surgical anastomosis Survival |
| title | Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial |
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