Background: The prognosis of patients with Epidermal Growth Factor Receptor (EGFR) overexpression in inoperable Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN) remains poor. Nimotuzumab is an Anti ...Background: The prognosis of patients with Epidermal Growth Factor Receptor (EGFR) overexpression in inoperable Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN) remains poor. Nimotuzumab is an Anti EGFR humanized monoclonal antibody approved for treatment of LASCCHN, with concurrent chemoradiation. Objective: To assess the efficacy and safety of nimotuzumab with concurrent chemoradiation in inoperable LASCCHN patients. Methodology: This is a single-centre, single arm, retrospective study evaluating 35 patients with histologically confirmed inoperable LASCCHN (stages III-IV). The patients were administered IV cisplatin 50 mg/m2 and IV nimotuzumab 200 mg for 6 - 7 weeks, along with radiotherapy of 6600 - 7000 cGy over 35 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 12 weeks after the last cycle of chemotherapy. They were also followed up for overall survival and relapse free survival. Results: The median duration of follow-up was 20 months. The most common site of cancer was oropharynx (68.6%). One patient was lost to follow up. Objective Response Rate (ORR) was observed in 97% of the patients with 17 patients (48.6%) achieving complete response (CR) and 17 patients (48.6%) achieving partial response (PR). The median overall survival was 22.7 months (95% CI: 21.30, 34.27). The median relapse free survival was 16.7 months (95% CI: 9.80, 24.50). Nimotuzumab was safe and well tolerated with few mild, self-limiting adverse events. Conclusion: Nimotuzumab with chemoradiation is a safe and efficacious option in patients with LASCCHN. Larger studies are needed to verify the same.展开更多
Background: Head and neck cancers (HNCs) constitute 5% of all cancers globally and are the most common cancers in India. Chemotherapy and radiotherapy have not been proved to be effective in advanced cases and the pro...Background: Head and neck cancers (HNCs) constitute 5% of all cancers globally and are the most common cancers in India. Chemotherapy and radiotherapy have not been proved to be effective in advanced cases and the prognosis remains dismal. This underscores the need for newer treatment options in these cases. Nimotuzumab, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was safer when combined with chemo- or radio-therapy. Aim: To evaluate the safety and efficacy of concurrently administered nimotuzumab with chemo-radiotherapy in patients with advanced inoperable squamous cell carcinomas of head and neck (LASCCHN). Methods:?This was an open-label, single arm study evaluating 57 patients with histologically confirmed inoperable LASCCHN (stages III and IV) and eastern co-operative oncology group (ECOG) performance status < 2. Informed consent was obtained from all patients. The patients were administered IV cisplatin 30 mg/m2?and IV nimotuzumab 200 mg weekly for 6 weeks, along with radiotherapy of 6600 cGy over 33 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 24 weeks after the last cycle of chemotherapy. Results: Mean age of patient was 50 years old (29 - 79 years old). The most common site of cancer was oral cavity (56.1%). Forty six patients (80.7%) completed 6 cycles of therapy. Objective response rate (ORR) was 80.7%, with 34 patients (59.6%) achieving complete response (CR), and 12 (21%) achieving partial response (PR). Stable disease (SD) was noted in 8 (14%) patients and progressive disease in 3 (5.2%) patients. Conclusion: Addition of nimotuzumab is a safe and efficacious option in patients with inoperable LASCCHN. Our observations confirm the available Phase II data. The long term survival benefits based on this encouraging response rate need to be further evaluated in this subset of cancer patients.展开更多
BACKGROUND Patients with recurrent or locally advanced head and neck squamous cell carcinoma(HNSCC)typically have limited treatment options and poor prognosis.AIM To evaluate the efficacy and safety of two drugs with ...BACKGROUND Patients with recurrent or locally advanced head and neck squamous cell carcinoma(HNSCC)typically have limited treatment options and poor prognosis.AIM To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC.METHODS This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days.Intensitymodulated radiation therapy with a conventional fraction was delivered 5 days per week.Objective response rate(ORR),disease control rate,and toxicity were observed as primary endpoints.Overall survival(OS)and progression free survival were recorded and analyzed as secondary endpoints.RESULTS A total of 24 patients with HNSCC were enrolled.During the median 22.4-mo follow-up,both ORR and disease control rate were 100%.The one-year OS was 75%,and one-year progression-free survival(PFS)was 66.7%(median PFS was 15.1 mo).Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients,and patients who achieved complete response had better survival than those in the PR group(all P<0.05).The most common grade 1-4(100%)or grade 3-4 toxicities(75%)were hematological,and the most common grade 3-4 non-hematological toxicity was mucositis in 17(71%)patients.CONCLUSION Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability.Considering the high adverse event rate,the optimized dose and schedule must be further explored.展开更多
BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A ...BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors(ICIs).The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIM To evaluate the evidence on the effectiveness of ICIs in HNSCC,based on published phase-3 clinical trials.METHODS We searched PubMed,Cochrane Library,Embase,and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC(R/M HNSCC)and locally advanced head and neck squamous cell carcinoma(LAHNSCC).We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma,recurrent,metastatic,locally advanced,immunotherapy,immune checkpoint inhibitors,monoclonal antibodies,programmed cell death protein-1(PD-1),programmed death-ligand 1(PD-L1),cytotoxic T-lymphocyte associated protein-4(CTLA-4),and phase-3 clinical trial.A sensitive search filter was used to limit our results to randomized controlled trials.RESULTS Five phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far:Four in R/M HNSCC and one in LAHNSCC.In patients with R/M HNSCC,anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care(standard singleagent systemic therapy).While the net gain in overall survival(OS)with nivolumab was 2.4 mo[hazard ratio(HR)=0.69,P=0.01],that with pembrolizumab was 1.5 mo(HR=0.80 nominal P=0.0161).The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T-lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes.In the first-line setting,in R/M HNSCC,pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo(HR=0.77,P=0.0034)in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive(combined positive score>20)population compared to standard of care(EXTREME regime).In patients with PD-L1 positive R/M HNSCC,monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME.In LAHNSCC,immunotherapy using avelumab(an anti-PD-L1 agent)along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSION Anti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings,with acceptable toxicity profiles compared to standard therapy.There is no proven efficacy in the curative setting to date.展开更多
头颈部鳞状细胞癌(squamous cell carcinoma of the head and neck,SCCHN)是最常见的一类头颈部肿瘤。由于早期症状不典型,大多数SCCHN患者确诊时已处于局部晚期。以标准剂量顺铂为基础的同期放化疗(chemoradiotherapy,CRT)是局部晚期SC...头颈部鳞状细胞癌(squamous cell carcinoma of the head and neck,SCCHN)是最常见的一类头颈部肿瘤。由于早期症状不典型,大多数SCCHN患者确诊时已处于局部晚期。以标准剂量顺铂为基础的同期放化疗(chemoradiotherapy,CRT)是局部晚期SCCHN患者的标准非手术治疗模式。但同期CRT的近期和远期毒性问题不容忽视,对于无法耐受标准治疗强度的患者,在治疗策略的选择上要兼顾疗效、器官毒性和器官功能。几乎所有的SCCHN都会存在表皮生长因子受体(epidermal growth factor receptor,EGFR)过表达。抗EGFR单抗通过与EGFR结合,竞争性阻断内源性EGFR天然配体,阻碍EGFR二聚体的形成,抑制肿瘤细胞生长;此外,抗EGFR单抗可通过影响细胞周期、DNA损伤修复及血管生成等多种途径发挥放疗增敏作用。既往Ⅲ期临床研究表明,对比单纯放疗,放疗联合西妥昔单抗可显著改善局部晚期SCCHN患者的局部区域控制,延长总生存期。临床工作中合理地应用抗EGFR单抗仍面临诸多挑战,包括适用人群的判定标准、应用时机、联合方案的选择及不良事件管理等都需要进一步明确和规范。本共识专家组以循证医学证据为基础、相关指南为依据,经充分讨论形成《抗EGFR单抗治疗局部晚期头颈部鳞状细胞癌临床共识(2023年版)》。根据本共识的专家建议,局部晚期SCCHN患者在同期CRT前,应评估患者对标准剂量顺铂治疗的耐受性和治疗毒性。对于无法耐受标准剂量顺铂治疗的患者,或在接受多西他赛+顺铂+5-氟尿嘧啶(TPF)方案诱导化疗后出现顺铂相关毒性的患者,可选择放疗联合西妥昔单抗方案。对于有降期或器官功能保留需求、拟行诱导治疗的患者,标准诱导治疗方案为TPF方案,不能耐受TPF方案毒性的患者,可用西妥昔单抗替代5-氟尿嘧啶,采用TPE方案。安全性方面,放疗联合西妥昔单抗相关常见不良反应包括痤疮样皮疹、口腔黏膜炎、放射性皮炎等,可以通过治疗前预防、治疗过程中早期识别和及时干预进行全面、分级管理。展开更多
文摘Background: The prognosis of patients with Epidermal Growth Factor Receptor (EGFR) overexpression in inoperable Locally Advanced Squamous Cell Carcinoma of Head and Neck (LASCCHN) remains poor. Nimotuzumab is an Anti EGFR humanized monoclonal antibody approved for treatment of LASCCHN, with concurrent chemoradiation. Objective: To assess the efficacy and safety of nimotuzumab with concurrent chemoradiation in inoperable LASCCHN patients. Methodology: This is a single-centre, single arm, retrospective study evaluating 35 patients with histologically confirmed inoperable LASCCHN (stages III-IV). The patients were administered IV cisplatin 50 mg/m2 and IV nimotuzumab 200 mg for 6 - 7 weeks, along with radiotherapy of 6600 - 7000 cGy over 35 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 12 weeks after the last cycle of chemotherapy. They were also followed up for overall survival and relapse free survival. Results: The median duration of follow-up was 20 months. The most common site of cancer was oropharynx (68.6%). One patient was lost to follow up. Objective Response Rate (ORR) was observed in 97% of the patients with 17 patients (48.6%) achieving complete response (CR) and 17 patients (48.6%) achieving partial response (PR). The median overall survival was 22.7 months (95% CI: 21.30, 34.27). The median relapse free survival was 16.7 months (95% CI: 9.80, 24.50). Nimotuzumab was safe and well tolerated with few mild, self-limiting adverse events. Conclusion: Nimotuzumab with chemoradiation is a safe and efficacious option in patients with LASCCHN. Larger studies are needed to verify the same.
文摘Background: Head and neck cancers (HNCs) constitute 5% of all cancers globally and are the most common cancers in India. Chemotherapy and radiotherapy have not been proved to be effective in advanced cases and the prognosis remains dismal. This underscores the need for newer treatment options in these cases. Nimotuzumab, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was safer when combined with chemo- or radio-therapy. Aim: To evaluate the safety and efficacy of concurrently administered nimotuzumab with chemo-radiotherapy in patients with advanced inoperable squamous cell carcinomas of head and neck (LASCCHN). Methods:?This was an open-label, single arm study evaluating 57 patients with histologically confirmed inoperable LASCCHN (stages III and IV) and eastern co-operative oncology group (ECOG) performance status < 2. Informed consent was obtained from all patients. The patients were administered IV cisplatin 30 mg/m2?and IV nimotuzumab 200 mg weekly for 6 weeks, along with radiotherapy of 6600 cGy over 33 fractions. Patients were evaluated over response evaluation criteria in solid tumors (RECIST) criteria 24 weeks after the last cycle of chemotherapy. Results: Mean age of patient was 50 years old (29 - 79 years old). The most common site of cancer was oral cavity (56.1%). Forty six patients (80.7%) completed 6 cycles of therapy. Objective response rate (ORR) was 80.7%, with 34 patients (59.6%) achieving complete response (CR), and 12 (21%) achieving partial response (PR). Stable disease (SD) was noted in 8 (14%) patients and progressive disease in 3 (5.2%) patients. Conclusion: Addition of nimotuzumab is a safe and efficacious option in patients with inoperable LASCCHN. Our observations confirm the available Phase II data. The long term survival benefits based on this encouraging response rate need to be further evaluated in this subset of cancer patients.
基金Supported by Tianjin Science and Technology Plan Project,No. 19YFZCSY00170Tianjin Union Medical center,No. 2019YJ007Beijing medical and health foundation,No. F1814B
文摘BACKGROUND Patients with recurrent or locally advanced head and neck squamous cell carcinoma(HNSCC)typically have limited treatment options and poor prognosis.AIM To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC.METHODS This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days.Intensitymodulated radiation therapy with a conventional fraction was delivered 5 days per week.Objective response rate(ORR),disease control rate,and toxicity were observed as primary endpoints.Overall survival(OS)and progression free survival were recorded and analyzed as secondary endpoints.RESULTS A total of 24 patients with HNSCC were enrolled.During the median 22.4-mo follow-up,both ORR and disease control rate were 100%.The one-year OS was 75%,and one-year progression-free survival(PFS)was 66.7%(median PFS was 15.1 mo).Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients,and patients who achieved complete response had better survival than those in the PR group(all P<0.05).The most common grade 1-4(100%)or grade 3-4 toxicities(75%)were hematological,and the most common grade 3-4 non-hematological toxicity was mucositis in 17(71%)patients.CONCLUSION Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability.Considering the high adverse event rate,the optimized dose and schedule must be further explored.
文摘BACKGROUND The outcomes of patients diagnosed with head and neck squamous cell carcinoma(HNSCC)who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal.A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors(ICIs).The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIM To evaluate the evidence on the effectiveness of ICIs in HNSCC,based on published phase-3 clinical trials.METHODS We searched PubMed,Cochrane Library,Embase,and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC(R/M HNSCC)and locally advanced head and neck squamous cell carcinoma(LAHNSCC).We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma,recurrent,metastatic,locally advanced,immunotherapy,immune checkpoint inhibitors,monoclonal antibodies,programmed cell death protein-1(PD-1),programmed death-ligand 1(PD-L1),cytotoxic T-lymphocyte associated protein-4(CTLA-4),and phase-3 clinical trial.A sensitive search filter was used to limit our results to randomized controlled trials.RESULTS Five phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far:Four in R/M HNSCC and one in LAHNSCC.In patients with R/M HNSCC,anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care(standard singleagent systemic therapy).While the net gain in overall survival(OS)with nivolumab was 2.4 mo[hazard ratio(HR)=0.69,P=0.01],that with pembrolizumab was 1.5 mo(HR=0.80 nominal P=0.0161).The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T-lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes.In the first-line setting,in R/M HNSCC,pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo(HR=0.77,P=0.0034)in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive(combined positive score>20)population compared to standard of care(EXTREME regime).In patients with PD-L1 positive R/M HNSCC,monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME.In LAHNSCC,immunotherapy using avelumab(an anti-PD-L1 agent)along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSION Anti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings,with acceptable toxicity profiles compared to standard therapy.There is no proven efficacy in the curative setting to date.
文摘头颈部鳞状细胞癌(squamous cell carcinoma of the head and neck,SCCHN)是最常见的一类头颈部肿瘤。由于早期症状不典型,大多数SCCHN患者确诊时已处于局部晚期。以标准剂量顺铂为基础的同期放化疗(chemoradiotherapy,CRT)是局部晚期SCCHN患者的标准非手术治疗模式。但同期CRT的近期和远期毒性问题不容忽视,对于无法耐受标准治疗强度的患者,在治疗策略的选择上要兼顾疗效、器官毒性和器官功能。几乎所有的SCCHN都会存在表皮生长因子受体(epidermal growth factor receptor,EGFR)过表达。抗EGFR单抗通过与EGFR结合,竞争性阻断内源性EGFR天然配体,阻碍EGFR二聚体的形成,抑制肿瘤细胞生长;此外,抗EGFR单抗可通过影响细胞周期、DNA损伤修复及血管生成等多种途径发挥放疗增敏作用。既往Ⅲ期临床研究表明,对比单纯放疗,放疗联合西妥昔单抗可显著改善局部晚期SCCHN患者的局部区域控制,延长总生存期。临床工作中合理地应用抗EGFR单抗仍面临诸多挑战,包括适用人群的判定标准、应用时机、联合方案的选择及不良事件管理等都需要进一步明确和规范。本共识专家组以循证医学证据为基础、相关指南为依据,经充分讨论形成《抗EGFR单抗治疗局部晚期头颈部鳞状细胞癌临床共识(2023年版)》。根据本共识的专家建议,局部晚期SCCHN患者在同期CRT前,应评估患者对标准剂量顺铂治疗的耐受性和治疗毒性。对于无法耐受标准剂量顺铂治疗的患者,或在接受多西他赛+顺铂+5-氟尿嘧啶(TPF)方案诱导化疗后出现顺铂相关毒性的患者,可选择放疗联合西妥昔单抗方案。对于有降期或器官功能保留需求、拟行诱导治疗的患者,标准诱导治疗方案为TPF方案,不能耐受TPF方案毒性的患者,可用西妥昔单抗替代5-氟尿嘧啶,采用TPE方案。安全性方面,放疗联合西妥昔单抗相关常见不良反应包括痤疮样皮疹、口腔黏膜炎、放射性皮炎等,可以通过治疗前预防、治疗过程中早期识别和及时干预进行全面、分级管理。
