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      Nimotuzumab Combined with Induction Chemotherapy and Concurrent Chemoradiotherapy in Unresectable Locally Advanced Hypopharyngeal Carcinoma: A Single Institution Experience in China

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          Abstract

          Objective

          To investigate the curative and adverse effects (AEs) of additional use of nimotuzumab combined with induction chemotherapy and concurrent chemoradiotherapy in unresectable locoregionally advanced hypopharyngeal carcinoma.

          Patients and Methods

          We retrospectively evaluated 36 patients with stage III or IVA hypopharyngeal carcinoma who received induction chemotherapy followed by concurrent chemoradiotherapy with or without nimotuzumab. The induction chemotherapy included two or three cycles of TPF regimen. The intensity-modulated radiation therapy (IMRT) dose was 70 Gy to the planning target volume. Concurrent with radiotherapy, patients received chemotherapy consisting of cisplatin q3w. Adjuvant chemotherapy consisting of TPF regimen was administered 1 month later after concurrent chemoradiotherapy. Nimotuzumab (200 mg day 1, q3w) was given to patients concurrently with induction chemotherapy and was administered concurrently with IMRT at a weekly dose of 200 mg.

          Results

          After induction chemotherapy, the objective response rate in patients treated with nimotuzumab (group A) versus those treated without nimotuzumab (group B) was 91.7% versus 58.3% (p=0.029). After concurrent chemoradiotherapy, the objective response rate was 95.8% in group A versus 83.3% in group B (p=0.253). The median follow-up was 22.6 months (range 8.9–39.5 months). The 2-year OS rate in group A and group B were 62.5% (95% CI 55–70%) and 51.8% (95% CI 45–59%), respectively, the 2-year OS rate in group A was better than group B, P<0.05. PFS was 23 months (95% CI 19–27) in group A versus 18 months (95% CI 12–22) in group B, PFS was longer in group A than group B, P<0.05. There was no significant difference in AEs between the two groups.

          Conclusion

          Additional use of nimotuzumab combined with induction chemotherapy and concurrent chemoradiotherapy in unresectable locoregionally advanced hypopharyngeal carcinoma yielded better short-term efficacy, also may improve overall survival and progression-free survival than patients without using nimotuzumab. The toxicity was tolerable.

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          Most cited references24

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          Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy.

          To evaluate the efficacy and safety of the epidermal growth factor receptor-directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy. An open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) for > or = 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase). From June 2001 to December 2002, 103 patients were enrolled and treated with cetuximab, 53 of whom subsequently received combination therapy. In the single-agent phase, response rate was 13%, disease control rate (complete response/partial response/stable disease) was 46%, and median time to progression (TTP) was 70 days. During the combination-therapy phase, the objective response rate was zero, disease control rate was 26%, and TTP was 50 days. Median overall survival was 178 days. Treatment was well tolerated. The most common cetuximab-related adverse events in the single-agent phase were skin reactions, particularly rash (49% of patients, mainly grade 1 or 2). There was one treatment-related death due to an infusion-related reaction. Single-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.
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            Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck.

            The prognosis of patients with advanced head and neck cancer remain dismal. For this tumor type, elevated levels of EGFR are associated with a shorter disease free survival and time to treatment failure, reflecting a more aggressive phenotype. Nimotuzumab is a humanized monoclonal antibody that recognizes domain III of the extracellular region of the EGFR, within an area that overlaps with both the surface patch recognized by cetuximab and the binding site for EGF. In order to assess the efficacy of nimotuzumab in combination with radiotherapy, a controlled, double blind, randomized clinical trial was conducted in 106 advanced squamous cell carcinoma of the head and neck patients, mostly, unfit for chemoradiotherapy. Control patients received a placebo and radiotherapy. Treatment was safe and the most frequent adverse events consisted on grade I or II asthenia, fever, headache and chills. No skin rash was detected. A significant complete response rate improvement was found in the group of patients treated with nimotuzumab as compared to the placebo. In the intent to treat analysis, a trend towards survival benefit for nimotuzumab treated subjects was found. The survival benefit became significant when applying the Harrington-Fleming test, a weighted log-rank that underscores the detection of differences deferred on time. In addition, a preliminary biomarker investigation showed a significant survival improvement for nimotuzumab treated patients as compared to controls for subjects with EGFR positive tumors. All patients showed a quality of life improvement and a reduction of the general and specific symptoms of the disease.
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              Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients.

              Overexpression of epidermal growth factor receptor (EGFR) in many cancers makes it an attractive therapeutic target. This study evaluated the clinical utility of nimotuzumab, a monoclonal anti-EGFR antibody, used concurrently with radiotherapy (RT) and chemoradiotherapy (CRT) in squamous cell carcinoma of the head and neck (SCCHN).
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                CMAR
                cancmanres
                Cancer Management and Research
                Dove
                1179-1322
                11 May 2020
                2020
                : 12
                : 3323-3329
                Affiliations
                [1 ]Department of Clinical Oncology, Shengjing Hospital of China Medical University , Shenyang, Liaoning 110004, People’s Republic of China
                Author notes
                Correspondence: Song Gao Department of Clinical Oncology, Shengjing Hospital of China Medical University , 36 San Hao Street, Shenyang110004, People’s Republic of China Email gaogao0229@hotmail.com
                Article
                248392
                10.2147/CMAR.S248392
                7227783
                c6916dc0-cce0-4ebd-877f-ff828f15f9e1
                © 2020 Tian et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 05 February 2020
                : 21 April 2020
                Page count
                Figures: 1, Tables: 4, References: 26, Pages: 7
                Categories
                Original Research

                Oncology & Radiotherapy
                nimotuzumab,induction chemotherapy,chemoradiotherapy,unresectable,locoregionally advanced,hypopharyngeal carcinoma

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