Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial

Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and...

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Veröffentlicht in:The lancet oncology 2021-05, Vol.22 (5), p.716-726
Hauptverfasser: Lv, Xing, Cao, Xun, Xia, Wei-Xiong, Liu, Kui-Yuan, Qiang, Meng-Yun, Guo, Ling, Qian, Chao-Nan, Cao, Ka-Jia, Mo, Hao-Yuan, Li, Xian-Ming, Li, Zi-Huang, Han, Fei, He, Yu-Xiang, Liu, Yu-Meng, Wu, Shao-Xiong, Bai, Yong-Rui, Ke, Liang-Ru, Qiu, Wen-Ze, Liang, Hu, Liu, Guo-Ying, Miao, Jing-Jing, Li, Wang-Zhong, Lv, Shu-Hui, Chen, Xi, Zhao, Chong, Xiang, Yan-Qun, Guo, Xiang
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container_title The lancet oncology
container_volume 22
creator Lv, Xing
Cao, Xun
Xia, Wei-Xiong
Liu, Kui-Yuan
Qiang, Meng-Yun
Guo, Ling
Qian, Chao-Nan
Cao, Ka-Jia
Mo, Hao-Yuan
Li, Xian-Ming
Li, Zi-Huang
Han, Fei
He, Yu-Xiang
Liu, Yu-Meng
Wu, Shao-Xiong
Bai, Yong-Rui
Ke, Liang-Ru
Qiu, Wen-Ze
Liang, Hu
Liu, Guo-Ying
Miao, Jing-Jing
Li, Wang-Zhong
Lv, Shu-Hui
Chen, Xi
Zhao, Chong
Xiang, Yan-Qun
Guo, Xiang
description Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18–60 years with previously untreated, non-keratinising stage III–IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68–70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62–68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30–32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival betwe
doi_str_mv 10.1016/S1470-2045(21)00075-9
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However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18–60 years with previously untreated, non-keratinising stage III–IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68–70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62–68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30–32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9–81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7–80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69–1·39; log-rank p=0·92), with a difference of 0·5% (95% CI −7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (−6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3–4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. For the Chinese translation of the abstract see Supplementary Materials section.</description><identifier>ISSN: 1470-2045</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(21)00075-9</identifier><identifier>PMID: 33857411</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>5-Fluorouracil ; Adult ; Adverse events ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Cancer therapies ; Chemoradiotherapy ; Chemotherapy ; Cisplatin ; Clinical trials ; Creatinine ; Cyclobutanes - administration &amp; dosage ; Cyclobutanes - adverse effects ; Drug dosages ; Endoscopy ; Female ; Fluorouracil - administration &amp; dosage ; Fluorouracil - adverse effects ; Hematology ; Humans ; Hydration ; Immunotherapy ; Induction Chemotherapy ; International cooperation ; Intravenous administration ; Leukopenia ; Lymph nodes ; Lymphatic system ; Male ; Metastasis ; Middle Aged ; Mucositis ; Nasopharyngeal carcinoma ; Nasopharyngeal Carcinoma - mortality ; Nasopharyngeal Carcinoma - pathology ; Nasopharyngeal Carcinoma - therapy ; Nasopharyngeal Neoplasms - mortality ; Nasopharyngeal Neoplasms - pathology ; Nasopharyngeal Neoplasms - therapy ; Neoplasm Staging ; Neurotoxicity ; Neutropenia ; Organoplatinum Compounds - administration &amp; dosage ; Organoplatinum Compounds - adverse effects ; Patients ; Platinum ; Radiation therapy ; Radiotherapy Dosage ; Renal function ; Spinal cord ; Survival ; Throat cancer ; Toxicity ; Translation ; Tumors</subject><ispartof>The lancet oncology, 2021-05, Vol.22 (5), p.716-726</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><rights>2021. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-7c9899f911c2bcdc782ae3ed3e7951040e3cfcc8a19f3d3e4d7d99daf0cd350b3</citedby><cites>FETCH-LOGICAL-c445t-7c9899f911c2bcdc782ae3ed3e7951040e3cfcc8a19f3d3e4d7d99daf0cd350b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2519268162?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976,64364,64368,72218</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33857411$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lv, Xing</creatorcontrib><creatorcontrib>Cao, Xun</creatorcontrib><creatorcontrib>Xia, Wei-Xiong</creatorcontrib><creatorcontrib>Liu, Kui-Yuan</creatorcontrib><creatorcontrib>Qiang, Meng-Yun</creatorcontrib><creatorcontrib>Guo, Ling</creatorcontrib><creatorcontrib>Qian, Chao-Nan</creatorcontrib><creatorcontrib>Cao, Ka-Jia</creatorcontrib><creatorcontrib>Mo, Hao-Yuan</creatorcontrib><creatorcontrib>Li, Xian-Ming</creatorcontrib><creatorcontrib>Li, Zi-Huang</creatorcontrib><creatorcontrib>Han, Fei</creatorcontrib><creatorcontrib>He, Yu-Xiang</creatorcontrib><creatorcontrib>Liu, Yu-Meng</creatorcontrib><creatorcontrib>Wu, Shao-Xiong</creatorcontrib><creatorcontrib>Bai, Yong-Rui</creatorcontrib><creatorcontrib>Ke, Liang-Ru</creatorcontrib><creatorcontrib>Qiu, Wen-Ze</creatorcontrib><creatorcontrib>Liang, Hu</creatorcontrib><creatorcontrib>Liu, Guo-Ying</creatorcontrib><creatorcontrib>Miao, Jing-Jing</creatorcontrib><creatorcontrib>Li, Wang-Zhong</creatorcontrib><creatorcontrib>Lv, Shu-Hui</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Zhao, Chong</creatorcontrib><creatorcontrib>Xiang, Yan-Qun</creatorcontrib><creatorcontrib>Guo, Xiang</creatorcontrib><title>Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18–60 years with previously untreated, non-keratinising stage III–IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68–70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62–68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30–32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9–81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7–80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69–1·39; log-rank p=0·92), with a difference of 0·5% (95% CI −7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (−6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3–4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. For the Chinese translation of the abstract see Supplementary Materials section.</description><subject>5-Fluorouracil</subject><subject>Adult</subject><subject>Adverse events</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Cancer therapies</subject><subject>Chemoradiotherapy</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Clinical trials</subject><subject>Creatinine</subject><subject>Cyclobutanes - administration &amp; dosage</subject><subject>Cyclobutanes - adverse effects</subject><subject>Drug dosages</subject><subject>Endoscopy</subject><subject>Female</subject><subject>Fluorouracil - administration &amp; dosage</subject><subject>Fluorouracil - adverse effects</subject><subject>Hematology</subject><subject>Humans</subject><subject>Hydration</subject><subject>Immunotherapy</subject><subject>Induction Chemotherapy</subject><subject>International cooperation</subject><subject>Intravenous administration</subject><subject>Leukopenia</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mucositis</subject><subject>Nasopharyngeal carcinoma</subject><subject>Nasopharyngeal Carcinoma - mortality</subject><subject>Nasopharyngeal Carcinoma - pathology</subject><subject>Nasopharyngeal Carcinoma - therapy</subject><subject>Nasopharyngeal Neoplasms - mortality</subject><subject>Nasopharyngeal Neoplasms - pathology</subject><subject>Nasopharyngeal Neoplasms - therapy</subject><subject>Neoplasm Staging</subject><subject>Neurotoxicity</subject><subject>Neutropenia</subject><subject>Organoplatinum Compounds - administration &amp; dosage</subject><subject>Organoplatinum Compounds - adverse effects</subject><subject>Patients</subject><subject>Platinum</subject><subject>Radiation therapy</subject><subject>Radiotherapy Dosage</subject><subject>Renal function</subject><subject>Spinal cord</subject><subject>Survival</subject><subject>Throat cancer</subject><subject>Toxicity</subject><subject>Translation</subject><subject>Tumors</subject><issn>1470-2045</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFUc1u1DAQjhCIlsIjgCxxAWkDdhJvYi4IKn4iVeLAz9VyxpOuK68dbKfV3ngH3rBP0SPeTekNcZrR6PuZma8onjL6ilG2fv2VNS0tK9rwFxV7SSlteSnuFcd53JS86br7h36BHBWPYryglLWM8ofFUV13vG0YOy5ueqdnSMY7Ahvc-rTBoKYduTJpQ6wf1GRVMo4op8loZx_8HBQYSy4xxDkSMPFfiNFb669Qk2G3aAelzZ1BZkyZhy7FxSwmdY6k7_vrX7_7H--JU9FPGxV27hyVJaACGOe36k12In5CV1o1oF0R511p3IjB-GDSbkVCXsVvTUS9IuBdCnmRfZ_VIpKapGCUfVw8GJWN-OS2nhTfP374dvq5PPvyqT99d1ZC0_BUtiA6IUbBGFQDaGi7SmGNusZWcEYbijWMAJ1iYqzztNGtFkKrkYKuOR3qk-L5ojsF_3PGmORFfpDLlrLiTFTrjq2rjOILCoKPMeAop2C2-XjJqNznLQ95y32YsmLykLcUmffsVn0etqjvWH8DzoC3CwDzjZcGg4yQnw6oTUBIUnvzH4s_Hw7DVw</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>Lv, Xing</creator><creator>Cao, Xun</creator><creator>Xia, Wei-Xiong</creator><creator>Liu, Kui-Yuan</creator><creator>Qiang, Meng-Yun</creator><creator>Guo, Ling</creator><creator>Qian, Chao-Nan</creator><creator>Cao, Ka-Jia</creator><creator>Mo, Hao-Yuan</creator><creator>Li, Xian-Ming</creator><creator>Li, Zi-Huang</creator><creator>Han, Fei</creator><creator>He, Yu-Xiang</creator><creator>Liu, Yu-Meng</creator><creator>Wu, Shao-Xiong</creator><creator>Bai, Yong-Rui</creator><creator>Ke, Liang-Ru</creator><creator>Qiu, Wen-Ze</creator><creator>Liang, Hu</creator><creator>Liu, Guo-Ying</creator><creator>Miao, Jing-Jing</creator><creator>Li, Wang-Zhong</creator><creator>Lv, Shu-Hui</creator><creator>Chen, Xi</creator><creator>Zhao, Chong</creator><creator>Xiang, Yan-Qun</creator><creator>Guo, Xiang</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>202105</creationdate><title>Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial</title><author>Lv, Xing ; Cao, Xun ; Xia, Wei-Xiong ; Liu, Kui-Yuan ; Qiang, Meng-Yun ; Guo, Ling ; Qian, Chao-Nan ; Cao, Ka-Jia ; Mo, Hao-Yuan ; Li, Xian-Ming ; Li, Zi-Huang ; Han, Fei ; He, Yu-Xiang ; Liu, Yu-Meng ; Wu, Shao-Xiong ; Bai, Yong-Rui ; Ke, Liang-Ru ; Qiu, Wen-Ze ; Liang, Hu ; Liu, Guo-Ying ; Miao, Jing-Jing ; Li, Wang-Zhong ; Lv, Shu-Hui ; Chen, Xi ; Zhao, Chong ; Xiang, Yan-Qun ; Guo, Xiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-7c9899f911c2bcdc782ae3ed3e7951040e3cfcc8a19f3d3e4d7d99daf0cd350b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>5-Fluorouracil</topic><topic>Adult</topic><topic>Adverse events</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Cancer therapies</topic><topic>Chemoradiotherapy</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Clinical trials</topic><topic>Creatinine</topic><topic>Cyclobutanes - administration &amp; dosage</topic><topic>Cyclobutanes - adverse effects</topic><topic>Drug dosages</topic><topic>Endoscopy</topic><topic>Female</topic><topic>Fluorouracil - administration &amp; dosage</topic><topic>Fluorouracil - adverse effects</topic><topic>Hematology</topic><topic>Humans</topic><topic>Hydration</topic><topic>Immunotherapy</topic><topic>Induction Chemotherapy</topic><topic>International cooperation</topic><topic>Intravenous administration</topic><topic>Leukopenia</topic><topic>Lymph nodes</topic><topic>Lymphatic system</topic><topic>Male</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Mucositis</topic><topic>Nasopharyngeal carcinoma</topic><topic>Nasopharyngeal Carcinoma - mortality</topic><topic>Nasopharyngeal Carcinoma - pathology</topic><topic>Nasopharyngeal Carcinoma - therapy</topic><topic>Nasopharyngeal Neoplasms - mortality</topic><topic>Nasopharyngeal Neoplasms - pathology</topic><topic>Nasopharyngeal Neoplasms - therapy</topic><topic>Neoplasm Staging</topic><topic>Neurotoxicity</topic><topic>Neutropenia</topic><topic>Organoplatinum Compounds - administration &amp; dosage</topic><topic>Organoplatinum Compounds - adverse effects</topic><topic>Patients</topic><topic>Platinum</topic><topic>Radiation therapy</topic><topic>Radiotherapy Dosage</topic><topic>Renal function</topic><topic>Spinal cord</topic><topic>Survival</topic><topic>Throat cancer</topic><topic>Toxicity</topic><topic>Translation</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lv, Xing</creatorcontrib><creatorcontrib>Cao, Xun</creatorcontrib><creatorcontrib>Xia, Wei-Xiong</creatorcontrib><creatorcontrib>Liu, Kui-Yuan</creatorcontrib><creatorcontrib>Qiang, Meng-Yun</creatorcontrib><creatorcontrib>Guo, Ling</creatorcontrib><creatorcontrib>Qian, Chao-Nan</creatorcontrib><creatorcontrib>Cao, Ka-Jia</creatorcontrib><creatorcontrib>Mo, Hao-Yuan</creatorcontrib><creatorcontrib>Li, Xian-Ming</creatorcontrib><creatorcontrib>Li, Zi-Huang</creatorcontrib><creatorcontrib>Han, Fei</creatorcontrib><creatorcontrib>He, Yu-Xiang</creatorcontrib><creatorcontrib>Liu, Yu-Meng</creatorcontrib><creatorcontrib>Wu, Shao-Xiong</creatorcontrib><creatorcontrib>Bai, Yong-Rui</creatorcontrib><creatorcontrib>Ke, Liang-Ru</creatorcontrib><creatorcontrib>Qiu, Wen-Ze</creatorcontrib><creatorcontrib>Liang, Hu</creatorcontrib><creatorcontrib>Liu, Guo-Ying</creatorcontrib><creatorcontrib>Miao, Jing-Jing</creatorcontrib><creatorcontrib>Li, Wang-Zhong</creatorcontrib><creatorcontrib>Lv, Shu-Hui</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Zhao, Chong</creatorcontrib><creatorcontrib>Xiang, Yan-Qun</creatorcontrib><creatorcontrib>Guo, Xiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>The lancet oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lv, Xing</au><au>Cao, Xun</au><au>Xia, Wei-Xiong</au><au>Liu, Kui-Yuan</au><au>Qiang, Meng-Yun</au><au>Guo, Ling</au><au>Qian, Chao-Nan</au><au>Cao, Ka-Jia</au><au>Mo, Hao-Yuan</au><au>Li, Xian-Ming</au><au>Li, Zi-Huang</au><au>Han, Fei</au><au>He, Yu-Xiang</au><au>Liu, Yu-Meng</au><au>Wu, Shao-Xiong</au><au>Bai, Yong-Rui</au><au>Ke, Liang-Ru</au><au>Qiu, Wen-Ze</au><au>Liang, Hu</au><au>Liu, Guo-Ying</au><au>Miao, Jing-Jing</au><au>Li, Wang-Zhong</au><au>Lv, Shu-Hui</au><au>Chen, Xi</au><au>Zhao, Chong</au><au>Xiang, Yan-Qun</au><au>Guo, Xiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial</atitle><jtitle>The lancet oncology</jtitle><addtitle>Lancet Oncol</addtitle><date>2021-05</date><risdate>2021</risdate><volume>22</volume><issue>5</issue><spage>716</spage><epage>726</epage><pages>716-726</pages><issn>1470-2045</issn><eissn>1474-5488</eissn><abstract>Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18–60 years with previously untreated, non-keratinising stage III–IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1–5 and 22–26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68–70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62–68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30–32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9–81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7–80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69–1·39; log-rank p=0·92), with a difference of 0·5% (95% CI −7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (−6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3–4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. For the Chinese translation of the abstract see Supplementary Materials section.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33857411</pmid><doi>10.1016/S1470-2045(21)00075-9</doi><tpages>11</tpages></addata></record>
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subjects 5-Fluorouracil
Adult
Adverse events
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Cancer therapies
Chemoradiotherapy
Chemotherapy
Cisplatin
Clinical trials
Creatinine
Cyclobutanes - administration & dosage
Cyclobutanes - adverse effects
Drug dosages
Endoscopy
Female
Fluorouracil - administration & dosage
Fluorouracil - adverse effects
Hematology
Humans
Hydration
Immunotherapy
Induction Chemotherapy
International cooperation
Intravenous administration
Leukopenia
Lymph nodes
Lymphatic system
Male
Metastasis
Middle Aged
Mucositis
Nasopharyngeal carcinoma
Nasopharyngeal Carcinoma - mortality
Nasopharyngeal Carcinoma - pathology
Nasopharyngeal Carcinoma - therapy
Nasopharyngeal Neoplasms - mortality
Nasopharyngeal Neoplasms - pathology
Nasopharyngeal Neoplasms - therapy
Neoplasm Staging
Neurotoxicity
Neutropenia
Organoplatinum Compounds - administration & dosage
Organoplatinum Compounds - adverse effects
Patients
Platinum
Radiation therapy
Radiotherapy Dosage
Renal function
Spinal cord
Survival
Throat cancer
Toxicity
Translation
Tumors
title Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial
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