Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial

Tang, Lin; Chen, Dong Ping; Guo, Ling; Mo, Hao Yuan; Huang, Ying; Guo, Shan; Qi, Bin; Tang, Qing Nan; Wang, Pan; Li, Xiao Yun; Li, Ji Bin; Liu, Qing; Gao, Yuanhong; Xie, Fang; Liu, Li Ting; Yang, Li; Liu, Sai Lan; Xie, Hao; Lan, Yu; Sun, Xiang; Yan, Jin; Wu, Yu Chun; Luo, Dong Hua; Huang, Pei Yu; Xiang, Yan; Sun, Rui; Chen, Ming‐Yuan; Lv, Xing; Wang, Lin; Xia, Wei; Zhao, Chong; Cao, Ke; Qian, Chao‐Nan; Guo, Xiang; Hong, Ming; Nie, Zhi Qiang; Chen, Qiu Yan

doi:10.1016/s1470-2045(18)30104-9

Cited by 110 publications

(121 citation statements)

References 22 publications

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“…Combinations of DDP-based chemotherapies have been widely used to treat various cancers, including NPC (Agbale et al, 2016;Dugbartey et al, 2016;Sun et al, 2016). However, high-dose DDP is frequently associated with severe vomiting, ototoxicity, and hematotoxicity (Forastiere et al, 2003;Ang et al, 2014;Tang et al, 2018). In addition, clinical studies indicate that many patients acquire DDP resistance during cancer chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma

et al. 2020

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Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard administrations applied to treat nasopharyngeal carcinoma (NPC). However, the molecular changes and functions of DDP in NPC chemo-resistance remain poorly understood. In the present study, transcriptomic sequencing between 5-8F and 5-8F/DDP cells was performed to identify differential expression and alternative splicing (AS) characteristics in DDP-resistant NPC cells. Transcriptomic profiling identified 1,757 upregulated genes and 1,473 downregulated differentially expressed genes (DEGs). Bioinformatic analysis revealed that these DEGs were associated with or participated in important biological regulatory functions in NPC. Validation of 20 significant DEGs using quantitative real-time reverse transcription PCR showed that the expression patterns of 17 mRNAs were in accordance with the sequencing data. Intron retention was identified as the major AS event in chemoresistant cells. Furthermore, the expression level of matrix metalloproteinase 1 (MMP1), which was one of the most upregulated mRNAs in the chemoresistant cell lines, was significantly associated with the migration, invasion, and proliferation of NPC cells in vitro. Our study revealed that dysregulated genes and AS-mediated DDP chemoresistance might play important roles in NPC development and progression. Targeting aberrantly expressed genes might clarify the pathogenesis of NPC and contribute to developing new therapeutic strategies for NPC.

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Section: Introductionmentioning

confidence: 99%

Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma

et al. 2020

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“…For DCF regimens, the most frequent nonhematologic toxicities of grade ≥ 3 (nausea, anorexia, and hyponatremia) were observed in 10%-30% of patients [2]. The lower nonhematologic toxicity of UDON versus DCF is likely attributable to the substitution of nedaplatin for cisplatin, as suggested by a recent phase III study comparing concurrent chemoradiotherapy with nedaplatin versus that with cisplatin in patients with nasopharyngeal carcinoma of stage II-IVB, with the frequency of vomiting, nausea, and anorexia of grade 3 or 4 being significantly higher in the cisplatin arm [5]. Together, these data suggest that UDON is as effective as DCF and potentially less toxic in terms of nonhematologic events.…”

Section: Discussionmentioning

confidence: 91%

Phase II Trial of 5-Fluorouracil, Docetaxel, and Nedaplatin (UDON) Combination Therapy for Recurrent or Metastatic Esophageal Cancer

et al. 2018

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Lessons Learned. The 5‐fluorouracil, docetaxel, and nedaplatin (UDON) regimen was well tolerated and showed promising antitumor activity in terms of both objective response rate and survival for patients with advanced or recurrent esophageal squamous cell carcinoma in the first‐line setting. UDON may be an optimal treatment option for patients with advanced esophageal cancer who are unfit for docetaxel, cisplatin, and 5‐fluorouracil regimens. The high response rate as well as the rapid and marked tumor shrinkage associated with UDON suggest that further evaluation of this regimen in the neoadjuvant setting is warranted. Background. A phase II study was performed to evaluate the efficacy and safety of 5‐fluorouracil (5‐FU), docetaxel, and nedaplatin (UDON) combination therapy for untreated recurrent or metastatic esophageal cancer. Methods. Patients received intravenous nedaplatin (90 mg/m 2 ) on day 1, docetaxel (35 mg/m 2 ) on days 1 and 15, and 5‐fluorouracil (800 mg/m 2 ) on days 1–5 of a 4‐week cycle. The primary endpoint was response rate, with secondary endpoints including overall survival (OS), progression‐free survival (PFS), dysphagia score, and adverse events. Results. Between March 2015 and July 2017, 23 patients were enrolled. Of 22 evaluable patients, 16 and 4 individuals experienced a partial response and stable disease, respectively, yielding a response rate of 72.7% (95% confidence interval [CI], 49.8%–89.3%) and disease control rate of 90.9% (95% CI, 70.8%–98.9%). Median OS and PFS were 11.2 months (95% CI, 9.1 months to not reached) and 6.0 months (95% CI, 2.5–10.6 months), respectively. Eleven (64.7%) of the 17 patients with a primary lesion showed amelioration of dysphagia after treatment. Frequent adverse events of grade 3 or 4 included neutropenia (87.0%) and leukopenia (39.1%). Febrile neutropenia was observed in two patients (8.7%). Conclusion. This phase II study demonstrated promising antitumor activity and good tolerability of UDON.

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“…Some studies focusing on nedaplatin-based CCRT alone or carboplatin-based CCRT alone in locoregional advanced NPC showed equivalent outcomes with less toxicity and were greatly promising 9 , 11 . Chitapanarux Imjai and colleagues 11 made an effort to minimise the toxicities caused by cisplatin-based CCRT by replacing cisplatin with carboplatin, showing less gastrointestinal toxicities in the carboplatin arm.…”

Section: Introductionmentioning

confidence: 99%

“…Inversely, subsequent research 12 revealed that the addition of carboplatin to radiotherapy did not benefit locoregional advanced NPC patients, which indicated carboplatin was not appropriate for CCRT. Mai HQ's study indicated nedaplatin-based CCRT was an alternative treatment strategy to cisplatin-based CCRT in locoregional advanced NPC 9 . However, patients were treated with CCRT alone and without induction chemotherapy (IC) or adjuvant chemotherapy (AC) in Mai's study 9 .…”

Section: Introductionmentioning

confidence: 99%

Clinical value of nedaplatin-based chemotherapy combined with radiotherapy for locoregional advanced nasopharyngeal carcinoma: a retrospective, propensity score-matched analysis

Zhan¹,

Tao²,

Qiu³

et al. 2020

J. Cancer

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Aims: This study aimed to investigate the clinical value of induction chemotherapy (IC) with docetaxel, 5-fluorouracil plus nedaplatin followed by concurrent chemoradiotherapy (CCRT) with nedaplatin for locoregional advanced nasopharyngeal carcinoma (NPC). Materials and Methods: In total, 269 patients diagnosed with locoregional advanced NPC between June 2012 and June 2017 were retrospectively included and divided into two groups: IC (docetaxel plus nedaplatin and 5-fluorouracil) followed by nedaplatin-based CCRT (TNF + N group, n = 146) and IC (docetaxel plus cisplatin and 5-fluorouracil) followed by cisplatin-based CCRT (TPF + P group, n = 123). The Kaplan-Meier method and Cox proportional hazards model were applied to analyse survival and prognosis. After propensity score-matched (PSM), 113 patients remained in each group. Toxicities were compared between the two groups using the Chi-square test or Fisher's exact test. Results: The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) rates of the TNF + N and TPF + P groups were 90.7% vs. 92.3% ( P = 0.315), 78.9% vs. 79.4% ( P = 0.715), 82.4% vs. 85.1% ( P = 0.441) and 96.1% vs. 93.3% ( P = 0.414), respectively, with no significant difference in 3-year survival outcome between the two groups, and this outcome was confirmed after using PSM analyses. In the PSM cohort, a significant higher frequency of grade 3/4 vomiting was observed in the TPF + P group compared to the TNF + N group (22.1% vs. 0%, P = 0.000). However, 15.9% of patients in the TNF + N group had grade 3/4 thrombocytopenia in comparison with 6.2% in the TPF + P group ( P = 0.020). Conclusions: The TNF regimen followed by CCRT with nedaplatin is an alternative treatment strategy to the standard TPF regimen followed by CCRT with cisplatin for patients with locoregional advanced NPC.

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Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial

Cited by 110 publications

References 22 publications

Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma

Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma

Phase II Trial of 5-Fluorouracil, Docetaxel, and Nedaplatin (UDON) Combination Therapy for Recurrent or Metastatic Esophageal Cancer

Clinical value of nedaplatin-based chemotherapy combined with radiotherapy for locoregional advanced nasopharyngeal carcinoma: a retrospective, propensity score-matched analysis

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