A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer

Xia, Wei‐Xiong; Lv, Xing; Hu, Liang; Li, Guoying; Sun, Rui; Zeng, Qi; Li, Siwei; Mo, Hao‐Yuan; Han, Fei; Luo, Dong-Hua; Liu, Qing; Shi, Meng-Yun; Ye, Yan-Fang; Yang, Jing; Qiang, Meng‐Yun; Qiu, Wen‐Ze; Yu, Ya‐Hui; Liu, Kui‐Yuan; Huang, Xinyan; Li, Wang‐Zhong; Lv, Shu‐Hui; Cai, Zhuo‐Chen; Miao, Jingjing; Guo, Ling; Chen, Ming‐Yuan; Cao, Kejiang; Wang, Lin; Zhao, Chong; Huang, Pei‐Yu; Chen, Qiuyan; Hua, Yi-Jun; Tang, Lin‐Quan; Qian, Chao‐Nan; Mai, Hai‐Qiang; Guo, Xiang; Xiang, Yan‐Qun

doi:10.1158/1078-0432.ccr-20-4532

Cited by 19 publications

(18 citation statements)

References 36 publications

(90 reference statements)

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“…A recent report from China found that leukopenia and thrombocytopenia were more frequent in a weekly cisplatin arm compared with a 3-weekly cisplatin arm although the planned total dose of the weekly cisplatin arm was higher than that of the 3-weekly arm (240 mg/m 2 v 200 mg/m 2 ). 31 While recognizing this difference, these findings indicate the need for care in avoiding hematologic toxicities in the safety management of this regimen. More particularly, they suggest the importance to safety of dose selection, which takes account of both total and individual dosage.…”

Section: Discussionmentioning

confidence: 99%

Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial

Kiyota

Tahara

Mizusawa

et al. 2022

JCO

102

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PURPOSE The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m2) or with weekly cisplatin (40 mg/m2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.

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Section: Discussionmentioning

confidence: 99%

Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial

Kiyota

Tahara

Mizusawa

et al. 2022

JCO

102

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“…Given this evidence, updated reviews and guidelines recommended that a cumulative cisplatin dose of 200 mg/m 2 may be the optimal threshold . A recent study has shown that 2 cycles of triweekly cisplatin, 100 mg/m 2 , was noninferior to standard weekly cisplatin, 40 mg/m 2 , for patients with locoregionally advanced NPC . Another updated randomized phase 2 noninferiority trial also revealed that 2 cycles of triweekly cisplatin, 100 mg/m 2 , was noninferior to 3 cycles for patients with Epstein-Barr virus DNA levels of less than 4000 copies/mL …”

Section: Discussionmentioning

confidence: 99%

Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma

et al. 2022

JAMA Oncol

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added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear.OBJECTIVE To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma. DESIGN, SETTING, AND PARTICIPANTSThis randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1.INTERVENTIONS Patients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m 2 , day 1], intravenous cisplatin [60 mg/m 2 , day 1], and oral capecitabine [1000 mg/m 2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m 2 , day 1] and fluorouracil [800 mg/m 2 daily, days 1-5]), followed by chemoradiotherapy. MAIN OUTCOMES AND MEASURESThe primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, tumor response, and safety. RESULTS Overall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR,. Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group.CONCLUSIONS AND RELEVANCE This randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile.

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“…Characteristics of the selected studies are summarized in Table 1 . Six retrospective studies ( Jagdis et al, 2014 ; Tao et al, 2014 ; Meng et al, 2018 ; Zhu et al, 2018 ; Wang et al, 2019 ; Gundog et al, 2020 ) and two RCTs ( Lee et al, 2016 ; Xia et al, 2021 ) were included in the analysis. The RCTs included one phase II and one phase III clinical trials.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of weekly versus triweekly cisplatin treatment concomitant with radiotherapy for locally advanced nasopharyngeal carcinoma: A systematic review and pooled analysis

2023

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Background: Most nasopharyngeal carcinoma cases are diagnosed at an advanced stage due to their hidden anatomical structure and atypical clinical symptoms and often require chemoradiotherapy. Here, we present a systematic review and pooled analysis to synthesize existing research on the efficacy and adverse effects of weekly versus triweekly cisplatin chemotherapy concomitant with radiotherapy for locally advanced nasopharyngeal carcinoma (LANPC).Methods: We searched the PubMed, Embase, and Cochrane Library databases from inception to 1 September 2021, for relevant original research articles published in English. The literature search and data extraction were done independently by two investigators. We used random-effects models to provide point estimates [95% confidence interval (CI)] of overall response rate (ORR), overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and the incidence rate of adverse effects (AEs) and with subgroup analysis according to each study type. The primary endpoints were ORR, OS, and PFS; LRFS, DMFS, and grade ≥3 acute AEs were secondary endpoints.Results: In total, 2,305 patients of eight studies were included in this review. We found that patients who were administered cisplatin weekly or triweekly had no differences in ORR, OS, PFS, DMFS, LRFS, severe mucositis, dermatitis, nausea/vomiting or nephrotoxicity. Patients who were administered weekly cisplatin were at a higher risk of hematological toxicity compared with patients who received the chemotherapy triweekly.Conclusion: Our findings suggest that both regimens could be recommended as the standard of care for the chemoradiotherapy treatment of LANPC, the perceived benefit of lower toxicity with weekly cisplatin could not be established.

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A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer

Cited by 19 publications

References 36 publications

Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial

Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial

Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma

Efficacy and safety of weekly versus triweekly cisplatin treatment concomitant with radiotherapy for locally advanced nasopharyngeal carcinoma: A systematic review and pooled analysis

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