A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent,persistent or metastatic cervical cancer

Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m² as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m²) or cisplatin (50 mg/m²) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5–96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.     

The developing trend of monoclonal antibodies in the treatment of colorectal cancer

Monoclonal antibodies (mAbs) against growth factors, receptors and tumor-specific/tumor-selective antigens represent a rapidly growing class of pharmaceutical agents which are poised to make a major impact on the treatment of colorectal cancer. mAbs targeting the epidermal growth factor receptor and the vascular endothelial growth factor have already been approved for the treatment of metastatic colorectal cancer. Other antibodies to the same and other molecular targets implicated in tumor growth and metastasis are undergoing intense preclinical and clinical evaluation. In both the neoadjuvant and adjuvant clinical settings, although mAbs are typically administered in combination with established cytotoxic chemotherapy regimens given their synergistic effect, several agents have demonstrated efficacy when given as monotherapy. At the same time, combination therapies with multiple targeted biological agents are actively being investigated. Existing clinical data and recent progress in preclinical and clinical studies of mAbs are reviewed.     

螺旋断层放疗联合抗表皮生长因子受体单抗治疗鼻咽癌的临床研究

目的探讨螺旋断层放疗联合抗表皮生长因子受体(anti-epidermal growth factor receptor,EGFR)单克隆抗体治疗鼻咽癌的近期疗效和不良反应。方法回顾性分析2008年3月-2009年11月我科收治的34例行根治性螺旋断层放疗的鼻咽癌患者临床资料。处方剂量:鼻咽部肿瘤(pGTVnx)及可见的转移淋巴结(pGTVnd)70Gy/33次,高危临床靶区(PTV1)60Gy/33次,预防照射区(PTV2)56Gy/33次,5次/周。其中17例放疗期间联合尼妥珠单抗,200mg/次,静滴,每周1次,共6-7次(尼妥珠组);另17例放疗期间联合西妥昔单抗,首次剂量400mg/m2,以后每周250mg/m2,静滴,每周1次,共6-7次(西妥昔组)。参照RECIST 1.0版实体瘤评价标准评价疗效,采用RTOG/EROTC标准评价急性反应。结果随访27-48个月,中位随访时间36个月。放疗后1、2、3年区域局部复发率、淋巴结复发率、远处转移生存率、总生存率,尼妥珠组均为0、0、17.6%和88.2%,西妥昔组均为0、0、11.8%和100%,两组差异无统计学意义。放疗后急性反应,尼妥珠组口腔黏膜反应(u=2.25,P<0.05)、体重下降程度(t=2.56,P=0.02)、皮疹(u=4.36,P<0.01)较西妥昔组轻。结论螺旋断层放疗联合尼妥珠单抗与联合西妥昔单抗治疗鼻咽癌的1、2、3年临床疗效无差异,急性反应尼妥珠单抗较西妥单抗轻,但均可耐受。     

尼妥珠单抗在局部晚期食管癌治疗中的应用进展

局部晚期食管癌(local advanced esophageal carcinoma,LAEC)无法通过手术根治,目前首选的治疗方法是根治性同期化放疗,但远期生存率仍不理想。尼妥珠单抗是一种新型人表皮生长因子受体单克隆抗体,细胞实验证实该药与化、放疗具有协同增效作用,近年来对该药与化、放疗联合治疗局部晚期食管癌的研究逐年增加,本文旨在对尼妥珠单抗治疗局部晚期食管癌的最新进展进行综述。     

Nimotuzumab Combined with Neoadjuvant or Induction Chemotherapy for Head and Neck Squamous Cell Carcinoma: A Retrospective Study

Objective: To assess the efficacy and toxicity of nimotuzumab combined with neoadjuvant or induction chemotherapy for head and neck squamous cell carcinoma (HNSCC). Methods: Patients received intravenous nimotuzumab (400 mg, weekly for 1–3 weeks) combined with chemotherapy (5-fluorouracil/paclitaxel/docetaxel + nedaplatin/cisplatin for 1–2 cycles), prior to definitive surgical resection, radiotherapy or other treatments. The primary endpoint was the objective response rate (ORR). The secondary endpoints were tumor downstaging, complete response rate (CRR), partial response rate (PRR), disease control rate (DCR), R0 resection rate, pathological complete response (pCR), larynx preservation rate, overall survival (OS), progression-free survival (PFS), and safety. Results: A total of 71 HNSCC patients with T_1-4N_0-2M₀ were enrolled. After neoadjuvant/induction chemotherapy, the ORR in patients with hypopharyngeal and laryngeal cancer was 100% and 76.1%, respectively. The DCR was 100% in both groups. The T downstaging in patients with hypopharyngeal and laryngeal cancer was 64.0% and 50.0%, the N downstaging was 28.0% and 2.2% (p = 0.001), respectively. At the early stage and locally advanced stage, the T downstaging was 66.7% and 50.0%, the N downstaging was 0% and 16.0% (p = 0.128), respectively. The R0 resection rate and pCR in 39 patients receiving surgery were 94.9% and 20.5%, respectively. The larynx preservation rate was 73.2%. The median PFS was 29.2 months in patients with laryngeal cancer. A mild rash occurred in a single patient and no grade 4 adverse events were encountered. Conclusion: Nimotuzumab combined with neoadjuvant or induction chemotherapy achieved similar short-term efficacy and less adverse events compared with previous studies. The N downstaging rate in patients with hypopharyngeal cancer was significantly higher compared with patients with laryngeal cancer.     

尼妥珠单抗联合IMRT治疗老年局部晚期食管癌患者的疗效观察

目的:探讨尼妥珠单抗联合适型调强放射治疗（IMRT）在局部晚期老年食管癌患者中的疗效和安全性。方法:67例老年局部晚期食管癌患者随机分为试验组和对照组，试验组34例予尼妥珠单抗联合IMRT治疗，对照组33例只行IMRT治疗。结果:试验组与对照组的近期有效率（RR）分别为85.2%和63.6%，疾病控制率（DCR）分别为97.1%和81.8%，差异均有统计学意义(P＜0.05）；1、2、3年生存率虽然试验组较对照组有提高，但差异无统计学意义(P＞0.05）；2组不良反应相似，差异无统计学意义(P＞0.05）。结论:尼妥珠单抗联合IMRT可以明显提高局部晚期老年食管癌患者的RR和DCR，但未明显提高患者的1、2、3年生存率。     

晚期口腔颌面-头颈部鳞癌靶向治疗的进展浅析

晚期口腔颌面-头颈部鳞癌的治疗仍然是个巨大的挑战。尽管传统的手术、放疗及化疗已取得了很大的进展,但晚期口腔颌面-头颈部鳞癌的预后仍然较差,分子靶向药物为此带来了新的希望。目前针对口腔颌面-头颈部鳞癌的靶向治疗的靶点主要有表皮生长因子受体及血管内皮生长因子受体。前者的代表药物有西妥昔单抗及尼妥珠单抗,他们无论是单药治疗,还是与放化疗结合治疗,均表现出了良好的前景;后者的代表药物主要是贝伐单抗,也已经进行到临床Ⅲ期实验。靶向治疗为晚期口腔颌面-头颈部鳞癌的治疗提供了新的机遇。     

尼妥珠单抗联合放疗治疗晚期鼻咽癌患者的护理

目的总结晚期鼻咽癌患者应用尼妥珠单抗联合放疗的护理体会。方法回顾性分析2009年1月～2010年12月本院收治的23例应用尼妥珠单抗联合放疗治疗晚期鼻咽癌患者的临床资料,并总结护理要点。结果 23例患者均完成放疗,其中19例获得完全缓解,4例获得部分缓解,均取得了满意的近期疗效。结论晚期鼻咽癌患者应用尼妥珠单抗联合放疗的治疗方法是安全有效的,采取针对性的护理措施可以减少和改善患者治疗期间的不良反应,提高护理质量。