Highlights from the 42nd annual meeting of the American Society of Clinical Oncology Atlanta, GA, USA, 2-6 June 2006

The results of approximately 3700 preclinical and clinical studies were presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO) held 2-6 June 2006, in Atlanta, Georgia. The annual ASCO meeting is the largest forum in which oncology professionals from around the world report the latest advances in cancer research, encompassing a wide spectrum of subjects on molecular biology, prevention, diagnosis and therapy of tumours. The present report summarises some of the more important results of the studies presented at the meeting. In particular, the authors focused on findings from randomised Phase III trials that, in their opinion, are most likely to have an immediate effect on clinical practice. The top advances were grouped into four major themes (breast cancer, colorectal cancer, non-small cell lung cancer and selected presentations from the plenary session). In addition, selected Phase I and II studies on promising novel therapeutic agents were briefly described. Finally, a 'question and answer' format was adopted to report results of interesting studies on some hot topics.     

Selected Highlights from the 26th San Antonio Breast Cancer Symposium

The San Antonio Breast Cancer Symposium is one of the largest international meetings devoted solely to breast cancer research. Basic scientists, translational researchers, clinical investigators and physicians share state-of-the-art information on breast cancer covering almost all the aspects of breast cancer, including prevention, aetiology, diagnosis, molecular biology and treatment. The current report describes relevant therapeutic findings that were presented at the 26^th San Antonio Breast Cancer Conference, held in San Antonio, Texas, USA, in December 2003.     

2014年美国第50届临床肿瘤年会乳腺癌内科治疗热点撷英

2014年美国临床肿瘤年会（ASCO）在芝加哥召开,大会报告了乳腺癌领域重要的基础研究成果和临床研究数据。本文主要综述了乳腺癌内科治疗领域4项主要临床研究结果：①与他莫西芬+卵巢功能抑制相比,依西美坦+卵巢功能抑制也可以用于激素受体阳性的绝经前早期乳腺癌,但年轻患者要充分做到卵巢功能抑制。②在辅助曲妥珠单抗治疗的基础上联合拉帕替尼没有获得改善HER2阳性乳腺癌的预后。③贝伐珠单抗联合化疗辅助治疗HER2阴性乳腺癌没有获得总生存的改善。④依西美坦+贝伐珠单抗用于转移性乳腺癌维持治疗在治疗周期上有一定延长。本文对乳腺癌内科治疗的进展进行了综述报道。     

非小细胞肺癌晚期靶向药物治疗中血清肿瘤标志物预测疗效的临床意义

目的:探讨晚期非小细胞癌患者靶向治疗前后血清肿瘤标志物预测疗效的临床意义。方法:对抽取的90例晚期非小细胞肺癌患者采用靶向药物治疗,评价治疗前后血清标志物水平的变化及近期疗效。结果:41例部分缓解(PR),31例稳定病变(SD),18例进展(PD),有效率45.56%;PR组、SD组、PD组的CEA、CA125、Cyfra21-1、SCCAg、NSE治疗前后的差值经方差分析,差异有统计学意义(F=36.172,P=0.000),PR组的差值高于其他两组,差异有统计学意义(P<0.05);治疗后较治疗前有效组的CEA、CA125、Cyfra21-1、SCCAg、NSE均显著降低且差异具有统计学意义(P<0.05),治疗后有效组和对照组的各指标差值比较差异具有统计学意义(P<0.05)。结论:血清肿瘤标志物水平能有效的预测靶向治疗药物治疗晚期非小细胞肺癌的疗效,有重要临床参考价值。     

Hot topics and landmark studies from the 43rd annual meeting of the American Society of Clinical Oncology

The results of several preclinical and clinical studies were reported by oncology professionals at the 43rd American Society of Clinical Oncology (ASCO) meeting, the largest international forum in which the latest achievements in cancer research are annually presented. The central theme this year was 'Translating Research into Practice', emphasizing the goal of forging stronger links between basic research and clinical practice. This review offers a critical, summarized selection of several of the foremost studies presented at the meeting. The focus is on the findings from randomized phase III trials that, in the authors' opinion, are most likely to have an immediate effect on clinical practice.     

靶向人表皮生长因子受体3治疗非小细胞肺癌的研究进展

人表皮生长因子受体3（HER3/ERBB3）属于HER家族的成员,在多种癌症中广泛表达。在配体神经调节素激活下,HER3主要与表皮生长因子受体1（EGFR/ERBB1/HER1）和表皮生长因子受体2（HER2/ERBB2）形成异源二聚体,激活信号转导通路,促进肿瘤的发生和发展。研究表明,HER3不仅与非小细胞肺癌（NSCLC）的不良预后相关,且在患者耐药中起到重要作用,是NSCLC的潜在治疗靶点。目前,HER3靶向治疗药物尚未获得上市批准,但多个HER3靶向治疗药物已经进入临床试验阶段。通过对HER3与NSCLC的相关性以及目前正处于临床试验中的HER3靶向治疗NSCLC的药物进行介绍,为HER3靶向治疗药物的研发提供参考。     

Recent advances in the medical management of breast cancer: highlights from the 29th San Antonio Breast Cancer Conference

The 29th edition of the San Antonio Breast Cancer Symposium was attended by a total of > 8000 basic scientists, translational researchers, clinical investigators and physicians gathering from ~ 80 countries worldwide. This is the largest meeting focusing on breast cancer, encompassing a wide array of topics from prevention, aetiology and diagnosis to molecular biology and treatment. From the main presentations at the meeting, it seems clear that combined efforts at prevention and treatment of this disease have translated into small, but significant, achievements. Much of the research in the area is focused on improving the therapeutic ratio of available treatments by better selection of patients.     

易瑞沙在一线化疗失败非小细胞肺癌的疗效观察

目的观察易瑞沙对一线化疗失败非小细胞癌(NSCLC)的近期疗效、生存期及不良反应。方法将73例一线化疗失败的NSCLC患者随机分为两组,A组36例给予单药多西紫杉醇75 mg·m-2,d1,1次/3周,B组37例给予易瑞沙0.25口服,每日一次,随访观察两组近期疗效、6个月、1年生存率及毒副反应发生情况。结果 B组总缓解率高于A组(P0.05);两组6个月生存率比较差异无统计学意义(P0.05);B组1年生存率高于A组(P0.05);B组除了皮疹、腹泻外其他不良反应发生率低于A组(P0.05)。结论易瑞沙靶向治疗一线化疗失败的NSCLC,可获得较好的近期疗效,延长患者生存期,毒副反应轻,能够改善患者生活质量。     

Selumetinib for the treatment of non-small cell lung cancer

Introduction: KRAS is the most frequently mutated oncogene in NSCLC, occurring in around a third of patients. However, this largest genomically defined subgroup of lung cancer patients seem to remain ‘undruggable’, with any effective targeted therapy approved at the moment. The prognostic and predictive power and thus the clinical utility of KRAS oncogenic mutations in lung cancer are highly debated issues, not supportive of KRAS testing in clinical practice of NSCLC therapy.

Areas covered: A phase II trial in KRAS-mutant NSCLC had shown significant improvements in PFS and ORR in patients treated with selumetinib plus docetaxel compared to docetaxel alone. Disappointing data emerged from the next phase III trial in which the addition of selumetinib to docetaxel in patients with advanced KRAS mutant lung cancer did not improve survival or show clinical benefit.

Expert opinion: Promising strategies against this common mutation are under evaluation in clinical trials. Combination therapies represent a potential approach for overcoming this complex pathway and potentiating the activity of other antitumor agents, by simultaneous inhibition of the RAS–RAF–MEK–MAPK pathway. Identifying predictive biomarkers, and delineating de novo and acquired resistance mechanisms are essential for future clinical development of MEK inhibitors.     

Selected highlights from the 27th San Antonio Breast Cancer Symposium

The San Antonio Breast Cancer Symposium is now considered the most important international breast cancer meeting worldwide. On 8 – 11th December 2004, ～ 6700 participants attended the meeting and shared the latest findings from breast cancer research. All the main fields of breast cancer research and treatment were covered. This report will focus on the most relevant advancements in the pharmacotherapy of breast cancer. The selected presentations have been grouped together in separate sections, including the fields of prevention, early disease and advanced disease. The most promising data from translational research have also been included, with particular regard to those who will most likely influence the management of breast cancer patients in the future.     

非小细胞肺癌全脑放疗复发后替莫唑胺联合立体定向放疗补救治疗临床观察

目的评价非小细胞肺癌(NSCLC)全脑放疗后颅内失败采用替莫唑胺联合立体定向治疗挽救的价值。方法 54例患者进入本次研究,所有全脑放疗后颅内复发转移的患者接受替莫唑胺化疗联合立体定向放疗,分析局控率,生存率情况,多因素分析确定和生存相关的预后因素。结果随访率100%,中位随访时间为13个月。全组中位生存时间为11.7个月。独立递归分级指数(RPA)1,2,3级中位生存期分别为19,14,9个月。自脑转移开始患者的中位生存时间为15个月(6～22个月),立体定向治疗加替莫唑胺挽救治疗后6和12个月局部控制率分别为93%和65%。结论联合治疗有较好的有效性和安全性,值得在NSCLC中颅内治疗失败后作为挽救治疗推广。     

Recent advances in the pharmacological treatment of colorectal cancer

Recent advances in the treatment of colorectal cancer have lead to significant gains in response rates and survival. The combination of newer agents such as irinotecan and oxaliplatin with 5-fluorouracil/leucovorin using various dosing schedules in the metastatic setting has resulted in a steady improvement in the outcome of patients with colorectal cancer. Experimental therapies such as epidermal growth factor receptor inhibitors, vascular endothelial growth factor inhibitors and cyclooxygenase-2 inhibitors, have shown promise in early clinical trials and have acceptable toxicity profiles. Efforts towards improving risk-stratification of stage II colorectal cancer patients and optimising therapy in patients with advanced disease, have focused on molecular and genetic markers. It is hoped that the addition of new therapies to existing drug combinations, as well as further advances in the understanding of colorectal cancer biology, will lead to further improvement in survival and quality of life for patients.     

NSCLC辅助化疗的分子标志物研究进展

作为一种全身性疾病,非小细胞肺癌（NSCLC）的治疗需要多学科的综合性治疗,越来越多的证据显示,术后辅助化疗能在不同程度上提高部分NSCLC患者的术后生存期,但大多数肺癌患者的术后生存期并没有根本性的提高.近年来随着肿瘤分子生物学的发展,我们发现非小细胞肺癌可能是一组在遗传学上完全不同的疾病,这导致了细胞学类型、细胞分化程度和病理分期均相同的患者,对同种化疗方案的疗效存在不同甚至相反的结果.基因组学和蛋白质组学研究针对NSCLC患者的一些具有疗效预测性的分子标志物,通过这些分子标志物,笔者成功地将相同组织学类型的NSCLC分成不同的亚型,从而实现肺癌的个体化治疗,最终改善患者预后.     

贝伐珠单抗联合化疗二线及以上治疗晚期非鳞型非小细胞肺癌的临床观察

目的：考察贝伐珠单抗联合化疗二线及以上治疗晚期非鳞型非小细胞肺癌的疗效和安全性。方法：28例经病理组织学或细胞学证实的晚期非鳞型非小细胞肺癌患者接受贝伐珠单抗联合化疗的二线及以上治疗,其间,贝伐珠单抗所用剂量为7.5mg·kg-1,在化疗第1d静滴给予;化疗方案包括培美曲塞加或不加铂类、白蛋白结合型紫杉醇加或不加铂类及替吉奥以及吉西他滨/紫杉醇/多西紫杉醇加或不加铂类。各治疗方案每3周为1个周期,持续4个周期,然后维持治疗,直至受试者不能耐受或疾病进展。按RECIST1.1版评价疗效,按NCI-CTC4.0版评价不良反应。结果：28例受试者中,无完全缓解病例,部分缓解11例（39.3%）,稳定16例（57.1%）,进展1例（3.6%）;客观缓解率为39.3%（11/28）,疾病控制率为96.4%（27/28）;中位无进展生存期为5个月,中位总生存期为10个月。亚组数据分析可见,贝伐珠单抗联合化疗各方案亚组中,培美曲塞方案受试者的中位无进展生存期为6个月,疗效最好,较其他各方案亚组有统计学差异（P=0.028）。安全性数据分析显示,与贝伐珠单抗相关的主要不良反应有Ⅰ~Ⅲ度高血压以及Ⅰ/Ⅱ度蛋白尿/出血/发热。结论：贝伐珠单抗联合化疗用于二线及以上治疗晚期非鳞型非小细胞肺癌的疗效较单纯化疗有一定改善,且毒副反应可耐受,对经济上可以接受的患者值得推荐使用。     

非小细胞肺癌4种化疗方案的不良反应比较

目的：比较治疗非小细胞肺癌的4种化疗方案的不良反应。方法：收集4种化疗方案(NP、GP、TP、NIP)所涉的208例化疗患者的不良反应，比较顺铂与不同抗肿瘤新药配伍的不良反应情况。结果：各组不良反应发生率最高的是血液学毒性，占不良反应的60％～70％，其次是消化道反应(15％～27％)。GP组的血红蛋白减少、血小板减少发生率高于其他组。NIP组白细胞减少、恶心、呕吐的发生率最高。TP组的神经毒性居4组首位。结论：必须重视抗肿瘤新药的不良反应。     

Novel combination chemotherapy in the treatment of non-small cell lung cancer

Treatment of patients with advanced non-small cell lung cancer (NSCLC) remains a vexing problem and long-term survival beyond 5 years is extremely rare. Five new agents, paclitaxel, docetaxel, vinorelbine, gemcitabine and irinotecan, have been introduced for the treatment of NSCLC and investigated extensively both preclinically and clinically. Monotherapy with one of these agents has produced survival benefits over the best supportive care in Phase III studies. Combination chemotherapy with a new agent and platinum produced a higher response rate than conventional cisplatin-based chemotherapy and improved survival was observed in some randomised trials. There was little difference in efficacy and toxicity between the chemotherapeutic regimens with a new agent and a platinum in Phase III trials, suggesting the clinical utility of these regimens is similar. Many trials have focused on regimens containing two new agents, with or without platinum. Preliminary results of Phase III trials of three drug combinations versus two drug combinations suggested the former to be more promising, in terms of response rates and survival. Whether the era of platinum-based chemotherapy in the treatment of NSCLC should continue or not must be determined by Phase III trials, evaluating the use of a platinum agent with one of the new agent combinations. These aggressive chemotherapeutic combinations will hopefully improve survival and quality of life for patients with advanced NSCLC.     

消癌平注射液联合TP方案治疗晚期非小细胞肺癌临床观察

目的:观察消癌平注射液联合TP方案治疗晚期非小细胞肺癌(NSCLC)的临床疗效。方法:78例晚期NSCLC患者随机分为对照组和治疗组。对照组:紫杉醇135mg/m2,第1天,静脉滴注,顺铂30mg/m2,第1天～第3天,静脉滴注(TP方案);治疗组:消癌平注射液联合TP方案,两组病例的临床资料具有可比性。均每21d为1个治疗周期。结果:治疗组在近期疗效、生活质量方面均优于对照组,差异有统计学意义(P<0.05);治疗组毒副反应略低。结论:消癌平注射液联合TP方案治疗晚期NSCLC的疗效较好,可有效改善临床症状,提高生存质量及降低不良反应。     

A phase I trial of the oral platinum analogue JM216 with concomitant radiotherapy in advanced malignancies of the chest

JM216 is an orally administered platinumanalogue. We undertook this study todetermine the maximally tolerated dose(MTD) of JM216 when administered withconcomitant radiotherapy to the chest(200 cGy daily, 5×/week) in patients withlocoregionally advanced non-small cell lung(NSCLC) or esophageal cancer. Patientswere excluded for inadequate bone marrowreserve, prior radiotherapy to the primarytumor or previous treatment with platinumdrugs. A dose-limiting toxicity (DLT) wasdefined using the National Cancer Institute(NCI) Common Toxicity Criteria (CTC) andconsisted of grade 2 renal, hepatic,cardiac, or pulmonary toxicity or grade 3hematologic, neurological, orgastrointestinal toxicity. A total of 23patients were registered; two neverreceived treatment and are excluded fromanalyses. Six patients were treated at adose of 30 mg/m²/day for 5 days withtwo grade 2 DLT's: cough (1 pt) andelevated trans-aminases (1 pt). Sevenevaluable patients were treated at60 mg/m²/day and seven experiencedgrade 3 or 4 toxicity, five related tomyelosuppression. The dose was thenreduced to 45 mg/m²/d. Eight patientswere evaluable for toxicity, of which 5experienced DLT: myelosuppression (3 pts),esophagitis (2 pts), dyspnea (1 pt), andelevated creatinine (1 pt). Fourteenpatients were evaluable for efficacy, ofwhich 6 had an objective response,including one complete response. Therecommended phase II dose of JM216 withconcurrent radiation therapy is30 mg/m²/d for 5 days. The major DLTis myelosuppression with only limitedincreased toxicity within the field ofradiation. This conceivably may limit theuse of JM216 as a radiation sensitizer.