西妥昔单抗联合化疗治疗转移性结直肠癌的临床观察

目的：观察西妥昔单抗联合含伊立替康或奥沙利铂化疗方案治疗转移性结直肠癌的近期疗效及毒副反应。方法：１０例经病理组织学确诊的转移性结直肠癌患者,给予西妥苷单抗联合ＦＯＬＦＩＲＩ方案或ＦＯＬＦＯＸ方案治疗,西妥昔单抗首次给予负荷剂量４００ｍｇ／ｍ^２,每周给予维持剂量为２５０ｍｇ／ｍ^２。结果：全组１０例患者中,完全缓解（ＣＲ）１例,部分缓解（ＰＲ）４例,稳定（ＳＤ）２例,进展（ＰＤ）３例,有效率为５０％,疾病控制率为７０％,中位肿瘤进展时间（ＴＴＰ）为６.４个月。主要毒副反应为痤疮样皮疹和腹泻。结论：西妥昔单抗联合ＦＯＬＦＩＲＩ方案或ＦＯＬＦＯＸ方案治疗转移性结直肠癌疗效较好,毒副反应可耐受。     

Cetuximab combination with chemotherapy in advanced non-small cell lung cancer

Objective  

To observe the efficacy and safety of cetuximab combined with chemotherapy in advanced non-small-cell lung cancer (NSCLC), and to investigate the association of status of K-RAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome.     

Locoregionally advanced head and neck cancer treated with primary radiotherapy: a comparison of the addition of cetuximab or chemotherapy and the impact of protocol treatment

PURPOSE: The addition of platinum-based chemotherapy (ChRT) or cetuximab (ExRT) to concurrent radiotherapy (RT) has resulted in improved survival in Phase III studies for locoregionally advanced head and neck cancer (LAHNC). However the optimal treatment regimen has not been defined. A retrospective study was performed to compare outcomes in patients who were treated definitively with ExRT or ChRT. METHODS: Cetuximab with concurrent RT was used to treat 29 patients with LAHNC, all of whom had tumors of the oral cavity, oropharynx, or larynx. All patients were T2 to T4 and overall American Joint Committee on Cancer Stage III to IVB, with a Karnofsky Performance Status (KPS) score of 60 or greater. ChRT was used to treat 103 patients with similar characteristics. Patients were evaluated for locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). Median follow-up for patients alive at last contact was 83 months for those treated with ExRT and 53 months for those treated with ChRT. Cox proportional hazard models were used to assess independent prognostic factors. RESULTS: The LRC, DMFS, and DSS were not significantly different, with 3-year rates of 70.7%, 92.4%, and 78.6% for ExRT and 74.7%, 86.6%, and 76.5% for ChRT, respectively. The OS was significantly different between the two groups (p = 0.02), with 3-year rates of 75.9% for ExRT and 61.3% for ChRT. OS was not significant when patients who were on protocol treatments of ExRT or ChRT were compared. Also, OS was not significant when multivariate analysis was used to control for potential confounding factors. CONCLUSION: In our single-institution retrospective review of patients treated with ExRT or ChRT, no significant differences were found in LRC, DMFS, DSS, or OS.     

mXELIRI和mFOLFIRI方案联合西妥昔单抗一线治疗转移性左半结肠癌的临床观察CSCD

目的初步比较mXELIRI与mFOLFIRI方案联合西妥昔单抗一线治疗转移性左半结肠癌的临床疗效及安全性。方法回顾性分析68例接受西妥昔单抗联合mXELIRI或mFOLFIRI方案治疗的转移性左半结肠癌患者临床资料,比较西妥昔单抗联合两种化疗方案的客观缓解率(ORR)、疾病控制率(DCR)及无进展生存时间(PFS),并评估安全性。结果mXELIRI组和mFOLFIRI组的客观缓解率分别为62.5%和58.4%,疾病控制率为87.5%和88.9%,中位PFS分别为10.5和9.9月,差异均无统计学意义(均P>0.05);mXELIRI组手足综合征发生率明显高于mFOLFIRI组(37.5%vs.13.9%,P=0.025)。结论西妥昔单抗联合mXELIRI或mFOLFIRI方案一线治疗转移性左半结肠癌的疗效及安全性相当。     

抗EGFR单抗类靶向药物在头颈部鳞癌综合治疗中的应用

头颈部肿瘤是世界上第6大常见的肿瘤。超过70%的头颈部肿瘤患者在首次确诊时即为局部晚期。尽管不断地努力改进治疗方法,但晚期病例的死亡率仍然居高不下。为了提高疗效,患者通常接受化疗、手术、放射治疗和分子靶向药物综合治疗。大量研究证实,表皮生长因子受体（epidermal growth factor receptor,EGFR）与肿瘤细胞的增殖和转移密切相关,EGFR在大多数头颈部肿瘤中高表达,对这些患者的预后有显著影响。抗EGFR单克隆抗体已经在一些国家被批准用于治疗局部晚期头颈鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）。本文综述了西妥昔单抗和尼妥珠单抗治疗HNSCC的研究进展。HNSCC的单克隆抗体靶向治疗,是选择西妥昔单抗还是尼妥珠单抗？本综述将围绕这一临床医生尤为关心的问题展开讨论。     

Perioperative Systemic Chemotherapy,Cytoreductive Surgery,and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab.

Evaluation of survival across several treatment lines in metastatic colorectal cancer: Analysis of the FIRE-3 trial (AIO KRK0306)

BackgroundWe explored the impacts of sequential application of various treatment lines on survival kinetics. Therefore, differences in overall survival (OS) observed in FIRE-3 were investigated in the context of time and exposure to applied treatment.Patients and methodsOS analyses (stratified by treatment with FOLFIRI plus either cetuximab or bevacizumab) were performed according to time intervals as well as using a Cox model to define changes of hazard ratio (HR) over time.ResultsThe fraction of patients with systemic treatment and time on treatment markedly decreases over treatment lines and time. OS evaluation by a Cox model indicated a trend towards a non-proportional hazard between treatment arms (P = 0.12/P = 0.09 for KRAS–intention-to-treat (ITT)/all-RAS wild-type populations, respectively). To improve the fit of the model, a change-point (point of curve separation) was estimated at 22.6 months (day 687) after randomisation. The HR between the two arms before 22.6 months was not significantly different from one. However, markedly different survival kinetics in favour of the cetuximab arm were apparent after the change-point (KRAS-ITT: P = 0.0018; HR, 0.60 [95% confidence interval [CI], 0.44–0.83] and RAS: P = 0.0006; HR, 0.51 [95% CI, 0.35–0.75]).ConclusionThe differences in OS favouring the cetuximab arm become apparent about 22.6 months after randomisation, indicating that only those patients who survive 22.6 months after randomisation benefit from the superiority of the cetuximab arm. When OS curves separate, only few patients receive active systemic treatment in short courses, suggesting that earlier treatment effects are responsible for later kinetics of survival curves.     

Cetuximab with radiotherapy as an alternative treatment for advanced squamous cell carcinoma of the temporal bone

The prognosis of advanced temporal bone cancer is poor, because complete surgical resection is difficult to achieve. Chemoradiotherapy is one of the available curative treatment options; however, its systemic effects on the patient restrict the use of this treatment. A 69-year-old female (who needed peritoneal dialysis) presented at our clinic with T4 left external auditory canal cancer and was treated with cetuximab plus radiotherapy (RT). The primary lesion showed complete response. The patient is currently alive with no evidence of disease two years after completion of the treatment and does not show any late toxicity. This is the first advanced temporal bone cancer patient treated with RT plus cetuximab. Cetuximab plus RT might be a treatment alternative for patients with advanced temporal bone cancer.     

Effective Treatment of Lung Adenocarcinoma Harboring EGFR-Activating Mutation,T790M,and cis-C797S Triple Mutations by Brigatinib and Cetuximab Combination Therapy

IntroductionAcquired resistance to osimertinib mediated by EGFR cis-C797S is now a growing challenge. No effective treatment strategy is currently available to overcome cis-C797S–mediated resistance.MethodsIn this retrospective cohort study, 15 patients with advanced lung adenocarcinoma and EGFR-activating mutation, T790M, and cis-C797S after osimertinib progression were identified by targeted next-generation sequencing. Five of these patients received a combined therapy of brigatinib and cetuximab, and 10 patients received cisplatin-based doublet chemotherapy.ResultsAmong the five patients who were positive for EGFR 19del-T790M-cis-C797S mutations, and who received brigatinib and cetuximab combination therapy, three patients achieved partial response, and two had stable disease, resulting in an overall objective response rate of 60% and disease control rate of 100%. Among the 10 patients who were positive for EGFR 19del or L858R-T790M-cis-C797S mutations and received chemotherapy, only one patient achieved partial response, five had stable disease, and the other four did not benefit from chemotherapy, resulting in an overall objective response rate and disease control rate of 10% and 60%, respectively. The median progression-free survival of patients who received combined targeted therapy was 14 months, and 3 months for those treated with chemotherapy. No grade III to IV adverse events were observed in any patient.ConclusionsOur retrospective study provides clinical evidence that a combined targeted therapy of brigatinib and cetuximab could be of benefit and may potentially be an effective treatment strategy to improve survival outcomes in patients who acquire EGFR T790M-cis-C797S–mediated resistance to osimertinib.