Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer

Suntharalingam, Mohan; Winter, Kathryn; Ilson, David H.; Dicker, Adam P.; Kachnic, Lisa A.; Konski, André; Chakravarthy, A. Bapsi; Anker, Christopher J.; Thakrar, H.; Horiba, Naomi; Dubey, Ajay Kumar; Greenberger, Joel S.; Raben, Adam; Giguere, Jeffrey K.; Roof, Kevin; Videtic, Gregory M.M.; Pollock, Jondavid; Safran, Howard; Crane, Christopher H.

doi:10.1001/jamaoncol.2017.1598

Cited by 159 publications

(145 citation statements)

References 28 publications

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“…The major acute adverse events in this study were myelosuppression and esophagitis, most of which were grades 1‐2. Grade 3 esophagitis occurred in 9.0% patients, similar with previous reports with radiotherapy of 50 Gy . A total of 2.3% of patients had grade 3 late esophageal strictures, which was 4‐5% in SIB studies .…”

Section: Discussionsupporting

confidence: 88%

Sequential boost of intensity‐modulated radiotherapy with chemotherapy for inoperable esophageal squamous cell carcinoma: A prospective phase II study

et al. 2020

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Purpose: This prospective phase II study aimed to determine the efficacy and tolerability of sequential boost of intensity-modulated radiation therapy (IMRT) with chemotherapy for patients with inoperable esophageal squamous cell carcinoma (ESCC). Methods: Patients with histologically or cytologically proven inoperable ESCC were enrolled in this study (ChiCTR-OIC-17010485). A larger target volume for subclinical lesion was irradiated with 50 Gy, and then, a smaller target volume only including gross tumor was boosted to 66 Gy. The fraction dose was 2 Gy, and no elective node was irradiated. Concurrent and consolidation chemotherapy of fluorouracil (600 mg/m 2 , days 1-3) plus cisplatin (25 mg/m 2 , days 1-3) was administered every 4 weeks, for 4 cycles in total. The primary endpoint was 2-year progressionfree survival (PFS). Results: Eighty-eight patients were enrolled in this study. The median age was 65 years (range: 45-75 years), and 69 patients (78.4%) were men. With the median follow-up of 26 (range: 3-95) months, the 2-and 5-year PFS were 39.3% and 36.9%, respectively, and overall survival (OS) were 57.1% and 39.2%, respectively. Tumor stage and concurrent chemotherapy were independent OS predictors. Major acute adverse events were myelosuppression and esophagitis, most of which were grades 1-2.Nine percent and 2.3% of patients had grade 3 acute esophagitis and late esophageal strictures, respectively. Conclusions: Sequential boost to 66 Gy by IMRT with chemotherapy was safe and effective for inoperable ESCC. A randomized phase III study to compare with standard dose of 50 Gy is warranted. K E Y W O R D Schemoradiotherapy, esophageal squamous cell carcinoma, intensity-modulated radiotherapy

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Section: Discussionsupporting

confidence: 88%

Sequential boost of intensity‐modulated radiotherapy with chemotherapy for inoperable esophageal squamous cell carcinoma: A prospective phase II study

et al. 2020

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“…The addition of cetuximab to concurrent CRT did not improve OS. These phase III trial results highlighted the need for predictive biomarkers in the treatment of EC (Table ) …”

Section: Treatmentsmentioning

confidence: 99%

Recent advancements in esophageal cancer treatment in Japan

Tanaka

Yoshida

Suetsugu

et al. 2018

Annals of Gastroent Surgery

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The 11th edition of the Japanese Classification of Esophageal Cancer (EC) was published in 2017. Some correction was made in the depth of tumor invasion to be consistent with the TNM classification by the Union for International Cancer Control (UICC). With regard to surgery, short‐term safety and long‐term effectiveness under thoracotomy/video‐assisted thoracoscopic surgery are expected to be proven by the Japan Clinical Oncology Group (JCOG)1409 study. Results of nutritional management and countermeasures for adverse events not only during the perioperative period but also during EC chemotherapy were reported. From now on, the pursuit of low invasiveness and radicality is desired. Esophageal surgery is also expected to be safe at all institutions. To determine the optimal modality of preoperative treatment and a novel chemo(radio)therapy regimen for patients with distant metastasis, the results of the ongoing JCOG1109 and 0807 studies are being released. The effect of the addition of molecular targeted drugs on chemotherapy and concurrent chemoradiation has not yet improved overall survival. Immune checkpoint inhibitor drugs could offer a potential new treatment approach for patients with treatment‐refractory advanced squamous cell carcinoma (SCC). The Cancer Genome Atlas Research Network reported the results of a comprehensive genome analysis and molecular analysis of SCC and adenocarcinoma of the esophagus. Further differentiation of SCC and adenocarcinoma by molecular characterization analysis may be useful for the development of clinical trials and targeted drug therapies as precision medicine. The era of ultimate minimally invasive surgery and personalized treatment has begun. Large, prospective studies will be required to confirm the value of these advancements.

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“…C225 in combination with EGFR not only blocked the secretion of TGF-and signal transduction but also decreased the expression of EGFR on the cell membrane surface (Liao and Carpenter, 2009). Clinically, C225 combined with radiotherapy showed a significant effect on head and neck squamous cell carcinoma and C225 combined with radiotherapy as a routine treatment on head and neck squamous cell carcinoma has been accepted by the majority of doctors (Sok et al, 2006;Pozzi et al, 2016;Suntharalingam et al, 2017 ;Weidhaas et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

EGFR inhibitor C225 Increases the Radio-Sensitivity of Human Breast Cancer Cells

Yao

Peng

et al. 2019

Asian Pac J Cancer Prev

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Objective: This study was undertaken to investigate the effect of C225 on the radio-sensitivity of MDA-MB-231 cells line and to disclosure underlying mechanism. Methods: CCK8 assay was used to measure the proliferation inhibition of C225 on MDA-MB-231 cells. The combined effects of C225 plus radiation on the proliferation of MDA-MB-231 cells were also evaluated by CCK-8 assay. The clonogenic assay was performed to evaluate the cell surviving fractions and to determine the radio-sensitizing effect of C225 on MDA-MB-231 cells. The apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blot analysis was used to detect the expression of p-EGFR, p-Akt, p-P38, and caspase-3. Results: C225 had an inhibiting effect on the proliferation of cells in a concentration-dependent manner. The cloning formation capacity was decreased in C225 plus radiation group. C225 increased radio-sensitivity of cells and led to cell cycle arrest in G0/G1 phase markedly. Cells treated with C225 and radiation predominantly exhibited G0/G1 phase arrest and significant decreased in the fraction of cells in the S phase. Moreover, C225 and radiation significantly increased the apoptosis rate of cells. Decreased cell proliferation was further supported by the down-regulation of p-EGFR and its downstream singling pathway proteins such as p-Akt and p-P38. The up-regulation of the Caspase-3 expression in C225 plus radiation group revealed that C225 could increase radiation-inducing cell apoptosis. Conclusion: C225 could increase the radio-sensitivity of cells, which may be due to the anti-proliferative synergistic effect between C225 and radiation as well as the down-regulation of the PI3K/Akt signaling pathway.

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Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer

Abstract: clinicaltrials.gov Identifier: NCT00655876.

Cited by 159 publications

References 28 publications

Sequential boost of intensity‐modulated radiotherapy with chemotherapy for inoperable esophageal squamous cell carcinoma: A prospective phase II study

Sequential boost of intensity‐modulated radiotherapy with chemotherapy for inoperable esophageal squamous cell carcinoma: A prospective phase II study

Recent advancements in esophageal cancer treatment in Japan

EGFR inhibitor C225 Increases the Radio-Sensitivity of Human Breast Cancer Cells

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