Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer

Wu, Shixiu; Wang, Lvhua; Luo, Hui; Xie, Congying; Zhang, Xuebang; Hu, Wei; Zheng, Aijuan; Li, Duojie; Zhang, Hongyan; Xie, Conghua; Lian, Xilong; Du, Dexi; Chen, Ming; Bian, Xiuhua; Tan, Bangxian; Jiang, Hao; Wang, Jianhua; Zhao, Jingbo; Xia, Bing; Ni, Zhaohui; Zhang, Ping; Li, Wenfeng; Zhao, Fangyu; Zou, Tian; Liu, Hui; Huang, Kaijun; Hu, Jin; Xie, Ruifei; Du, Lin; Li, Gang

doi:10.1016/j.ejca.2018.01.085

Cited by 24 publications

(30 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, we demonstrated that ge tinib and docetaxel was consistently synergistic. This observation is consistent with the demonstration that addition of erlotinib to chemoradiotherapy including paclitaxel was bene cial in ESCC (35). In this study there was no biomarker selection, and we hypothesise that in this trial the greatest bene t from addition of erlotinib will be seen in those patients who are EGFR CNG and/or have EGFR protein overexpression.…”

Section: Discussionsupporting

confidence: 88%

“…Several clinical trials have investigated the combination of EGFR inhibitors with cytotoxic chemotherapy or concurrent chemoradiotherapy (27)(28)(29)(30)35). In the palliative setting, in both ESCC and GOA the addition of EGFR inhibitors to platinum plus uoropyrimidine chemotherapy has not improved overall survival (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, in the radical treatment setting, the addition of EGFR inhibitors to concurrent chemoradiotherapy, with a platinum and uoropyrimidine chemotherapy backbone has not improved overall survival (27). However, addition of EGFR inhibition to chemoradiotherapy in ESCC with a chemotherapy backbone incorporating paclitaxel did improve overall survival, even in biomarker unselected patients (35). Consistent with these clinical trial results we observed that EGFR CNG positive gastroesophageal cancers in both the palliative and neoadjuvant setting appear to be more sensitive to platinum uoropyrimidine-based cytotoxic chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Con icting results have also been reported in trials of platinum-based chemotherapy in combination with EGFR TKi in non-small cell lung cancer patients (NSCLC) (31)(32)(33)(34). In contrast, the addition of the EGFR TKi erlotinib, to de nitive chemoradiotherapy for ESCC, which included a taxane (paclitaxel and cisplatin) was bene cial (35).…”

Section: Introductionmentioning

confidence: 94%

See 3 more Smart Citations

Interactions between anti-EGFR therapies and cytotoxic chemotherapy in oesophageal squamous cell carcinoma: Why clinical trials have failed and how they could succeed

Meemanage¹,

Spender²,

Collinson³

et al. 2020

Preprint

View full text Add to dashboard Cite

BACKGROUND Oesophageal squamous cell carcinoma (ESCC) has high mortality and poor prognosis. Advanced tumours are treated with fluoropyrimidine/platinum chemotherapy (PBC) followed by second-line irinotecan or taxane monotherapy, but resistance is common and new therapeutic approaches are needed. Approximately 20% of ESCC tumours carry copy number gain (CNG) of the epidermal growth factor receptor (EGFR) gene. Previous analysis of randomised clinical trials shows that anti-EGFR monotherapy benefits biomarker-selected patients with EGFR CNG and/or high expression by Immunohistochemistry (IHC). However, responses are often of short duration indicating that combining anti-EGFR therapy with other agents is required to optimise the benefit from anti-EGFR therapies even in biomarker selected patients. Randomised clinical trials have not shown benefit from the addition of anti-EGFR therapies to platinum fluoropyrimidine chemotherapy and uncertainty remains regarding the optimal cytotoxic chemotherapy partner for anti-EGFR therapies in ESCC. METHODS The effects of EGFR CNG on sensitivity to PBC in a cohort of gastroesophageal cancer patients (n = 302) was evaluated. Drug combination studies using the EGFR inhibitor gefitinib with cytotoxic chemotherapies, docetaxel, cisplatin, oxaliplatin and irinotecan, on cell proliferation and cell death of EGFR CNG ESCC cell lines were assessed. RESULTS EGFR CNG in gastroesophageal cancer patients was associated with better overall survival following platinum-based chemotherapy. Drug combination studies showed that co-administration of gefitinib and platinum-based cytotoxics was frequently antagonistic in cell-based assays in EGFR CNG ESCC, whereas the combination of gefitinib with docetaxel or irinotecan was more efficacious. Co-administration of gefitinib/docetaxel and sequential administration of docetaxel before gefitinib showed synergy, but docetaxel given after gefitinib was antagonistic. CONCLUSIONS Gefitinib/docetaxel co-administration demonstrated synergy and taxanes are likely to provide the most effective cytotoxic chemotherapy partner for anti-EGFR therapies in EGFR CNG-positive advanced ESCC. Combination of gefitinib and platinum-based cytotoxics was antagonistic suggesting anti-EGFR therapies might reduce anti-cancer effects of chemotherapy which could provide a key explanation for the lack of benefit for the addition of anti-EGFR therapies to PBC in randomised clinical trials. Our data suggest that the combination of docetaxel with anti-EGFR therapies, with careful consideration of dosing schedules, should be evaluated in advanced EGFR CNG-positive and/or IHC high EGFR expressing ESCC.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

See 2 more Smart Citations

Interactions between anti-EGFR therapies and cytotoxic chemotherapy in oesophageal squamous cell carcinoma: Why clinical trials have failed and how they could succeed

Meemanage¹,

Spender²,

Collinson³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, this trial confirmed that, aside from rash and radiation esophagitis, the incidence of grade 3 or greater toxicities were manageable and did not differ across the four groups. 42 Traditionally, it was thought that elderly patients have fewer body function reserves, shorter life expectancy, and more need for socioeconomic support than young patients. Therefore, this finding suggests that aggressive treatment decisions might not be suitable for this unique and challenging subpopulation.…”

Section: Discussionmentioning

confidence: 99%

Concurrent chemoradiation therapy tailored to the older adults with esophageal cancer: state of the art and the future

Song

Fang

Wu³

2018

CIA

View full text Add to dashboard Cite

PurposeThe aim of this study was to review the published literature addressing the question of whether geriatric assessment (GA) should be routinely applied in the treatment of older adults with esophageal cancer (EC) who have received definitive concurrent chemoradiotherapy (dCRT).Materials and methodsA literature search of PubMed, Embase, and Cochrane Library was performed. Studies that contained original data outlining the inclusion and exclusion criteria, treatment compliance rate, and severe toxicity reports were reviewed. Additionally, criteria from ongoing clinical trials in the World Health Organization and National Institutes of Health registries were reviewed to evaluate the utilization of GA-related domains in elderly EC patients who received dCRT.ResultsTwenty-nine studies were identified based on the selection criteria: five were single-arm prospective studies, and the other studies were retrospective studies. All studies used chronological age and performance status as basic descriptors for this subpopulation. The comorbidity index and the malnutrition level were mentioned in several studies. However, factors such as “Demographic data and social support,” “Psychology,” “Polypharmacy,” and “Geriatric syndromes” were not described in any of the included studies. Unfortunately, the results were similar for the registered clinical trials. Finally, treatment compliance and toxicity profile were found to be acceptable in selected elderly EC patients.ConclusionThe current experience for older adults with EC receiving dCRT is mainly based on the results of a series of retrospective studies. Ongoing clinical trials should routinely consider GA-related domains to select appropriate treatments for patients in the future.

show abstract

Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer

Wei³

et al. 2022

JAMA Netw Open

View full text Add to dashboard Cite

IMPORTANCE Multiple paclitaxel-based regimens are widely used in chemoradiation therapy against esophageal cancer, including regimens combining paclitaxel with fluorouracil, cisplatin, and carboplatin. However, which among these 3 regimens provides the best prognosis with minimum adverse events is still unknown. OBJECTIVE To compare the efficacy and adverse events of fluorouracil, cisplatin, and carboplatin in definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial of patients with ESCC was conducted in 11 treatment centers in China. Eligible patients were aged 18 to 75 years and had histologically confirmed ESCC stages IIa to IVa with no prior treatment, Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ functions. The study was conducted between July 2015 and February 2018, and the cutoff date for data analysis was August 31, 2020. INTERVENTIONS Patients with locally advanced ESCC were randomly assigned (1:1:1) to groups combining paclitaxel treatment with fluorouracil, cisplatin, or carboplatin. Patients in the cisplatin group were treated with 2 cycles of concurrent chemoradiotherapy followed by 2 cycles of consolidation chemotherapy with monthly paclitaxel plus cisplatin. For the fluorouracil group, patients were administered 6 cycles of weekly paclitaxel plus fluorouracil in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus fluorouracil in consolidation chemotherapy. Patients in the carboplatin group were treated with 6 cycles of weekly paclitaxel plus carboplatin in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus carboplatin in consolidation chemotherapy. All patients received radiotherapy of 61.2 Gy delivered in 34 fractions. MAIN OUTCOMES AND MEASURES The primary end point was overall survival (OS). The secondary end points were progression-free survival and adverse events. RESULTS Overall, 321 patients (median [IQR] age, 64 years [59-69 years]; 248 [77.3%] men) with ESCC from 11 centers were randomized into fluorouracil, cisplatin, or carboplatin groups between July 2015 and February 2018. Over a median (IQR) follow-up time of surviving patients of 46.0 months (36.6-53.0 months), the 3-year OS rates were 57.2% in the fluorouracil group, 60.1% in the cisplatin group, and 56.5% in the carboplatin group, respectively (fluorouracil vs cisplatin: HR, 1.06; 95% CI, 0.71-1.60; P = .77; fluorouracil vs carboplatin: HR, 0.94; 95% CI, 0.63-1.40; P = .77). The cisplatin group had significantly higher incidences of acute grade 3 or 4 neutropenia (69 events (continued) Key Points Question Which paclitaxel-based regimen, among fluorouracil, cisplatin, and carboplatin, provides the best prognosis with minimum adverse events for patients with locally advanced esophageal squamous cell carcinoma? Findings In this randomized clinical trial of 321 patients with esophageal squamous cell carcinoma treated in 11 cancer centers in China, th...

show abstract

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer

Cited by 24 publications

References 25 publications

Interactions between anti-EGFR therapies and cytotoxic chemotherapy in oesophageal squamous cell carcinoma: Why clinical trials have failed and how they could succeed

Interactions between anti-EGFR therapies and cytotoxic chemotherapy in oesophageal squamous cell carcinoma: Why clinical trials have failed and how they could succeed

Concurrent chemoradiation therapy tailored to the older adults with esophageal cancer: state of the art and the future

Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer

Contact Info

Product

Resources

About