Crizotinib治疗ALK阳性伴骨髓转移的肺腺癌1例及文献复习

背景与目的肺癌患者常伴远处转移,其中伴骨髓转移患者治疗手段有限,预后差。Crizotinib已被证实可用于治疗间变淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阳性的肺腺癌,但对于骨髓转移癌的疗效如何罕见报道。本文总结1例crizotinib治疗ALK阳性肺腺癌伴骨髓转移患者,并对其有效性及安全性进行讨论和分析。方法采用原位免疫荧光杂交法(fluorescence in situ hybridization,FISH)检测ALK融合基因阳性,一线化疗失败后给予crizotinib治疗,250 mg,2次/d。按照实体瘤疗效评价标准1.1版(Response Evaluation Criteriation in Solid Tumours,RECIST v1.1)评价客观疗效,采用骨髓活检评价骨髓转移瘤疗效。按照不良反应通用术语标准4.0版(Common Terminology Criteria for Adverse Events v4.0,CTC AE v4.0)评估用药期间发生的不良事件。结果该患者服用crizotinib 6周后,总体疗效评价为部分缓解(partial response,PR),骨髓疗效为完全缓解(complete response,CR)。因出现肺炎停药,无进展生存期(progression-free survival,PFS)20周,总生存期(overall survival,OS)22周。结论 Crizotinib治疗ALK阳性的肺癌伴骨髓转移患者可达骨髓完全缓解,耐受性好。     

厄洛替尼治疗脑脊液检测EGFR敏感突变的肺腺癌一例

背景与目的 脑是非小细胞肺癌(non-small cell lung cancer,NSCLC)常见的转移部位.有研究显示表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKI)可透过血脑屏障,发挥抗肿瘤作用.本例报道采用突变扩增阻滞系统(amplification refractory mutation system,ARMS)检测脑脊液EGFR突变指导临床治疗的可行性,并分析TKI治疗肺癌脑转移的疗效和安全性.方法 腰穿取得脑脊液标本,检测颅内压力,检验常规、生化及肿瘤标志物,查找脱落细胞,采用ARMS法检测EGFR基因突变,得到阳性结果后给予盐酸厄洛替尼(erlotinib,tarceva,特罗凯)治疗,150 mg,每天1次.按照实体瘤疗效评价标准1.1版(Response Evaluation Criteriation in Solid Tumours,RECIST v1.1)评价客观疗效,按照不良反应通用术语标准4.0版(Common Terminology Criteria for Adverse Events v4.0,CTC AE v4.0)评估用药期间发生的不良事件.结果 该患者多线治疗后,颅内病灶控制欠佳,脑脊液中发现异型细胞,EGFR基因19外显子缺失突变,服用厄洛替尼4周后,颅内客观疗效为部分缓解(partial response,PR),颅外客观疗效为疾病稳定(stable disease,SD),颅内无进展生存期(progression-free survival,PFS)10.5个月,总生存期(overall survival,OS)11个月.主要不良反应为皮疹(1级).结论 脑脊液检测EGFR突变可为制定治疗策略提供理论支持,根据不同的突变状态给予小分子靶向药物联合化疗,可分别控制颅内及颅外病灶.     

帕博丽珠单抗治疗晚期黑色素瘤的不良事件及相关性分析

背景与目的:免疫检查点抑制剂(immune checkpoint inhibitor,ICI)已成为肿瘤治疗的重要手段,然而伴随其显著疗效的是药物相关不良反应。观察帕博丽珠单抗在晚期黑色素瘤治疗中的安全性;初步探讨程序性死亡[蛋白]-1(programmed death-1,PD-1)单抗不良事件发生的预测因子及与疗效的相关性。方法:收集2016年8月-2017年7月期间在北京大学肿瘤医院入组一项"帕博丽珠单抗作为二线治疗中国局部晚期或转移性黑色素瘤的Ⅰb期临床研究(Keynote-151)"的54例患者的临床资料,包括性别、年龄、疾病分期、原发部位、既往化疗史、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分及基线外周血细胞计数,以及药物治疗相关不良事件和疗效相关信息。不良事件根据通用不良事件术语标准(Common Terminology Criteria Adverse Events,CTCAE)4.03版评价,疗效根据实体肿瘤疗效评价标准(Response Evaluation Criteria in Solid Tumors,RECIST)1.1标准评估。结果:帕博丽珠单抗在晚期黑色素瘤治疗中不良事件发生率达88.9%(48/54),严重不良事件发生率为13.0%(7/54),无死亡病例;肝毒性是导致中断和终止用药的主要原因;分析严重不良事件的发生与所观察各项临床特征及实验室检查指标之间均无显著相关性;不良事件的发生与疗效相关分析提示白癜风(P=0.001)和甲状腺功能异常(P=0.007)与疗效相关。结论:帕博丽珠单抗治疗晚期黑色素瘤不良反应发生率较高,但以1~2级为主,耐受性较好;肝毒性对试验药物应用影响最大;白癜风和甲状腺功能异常均可能是疗效较好的预测因子。     

克唑替尼联合脑转移灶切除、全脑放疗治疗ROS1阳性伴有症状脑转移的肺腺癌1例及文献复习

背景与目的伴有脑转移的肺癌预后差。克唑替尼可有效治疗ROS1（C-ros oncogene 1 receptor tyrosine kinase）融合基因阳性的肺癌,但由于血脑屏障通透率较低,对脑转移灶的治疗效果不佳。本文总结1例综合运用手术、全脑放疗+残留灶补量放疗及克唑替尼等手段治疗ROS1融合基因阳性伴有症状脑转移的肺腺癌患者,并对其有效性及安全性进行讨论和分析。方法采用手术切除占位效应明显、引起头疼症状的颅内病灶,获得病理;因ROS1融合基因阳性,给予克唑替尼治疗,250 mg,2次/d;术后进行全脑放疗+残留灶补量放疗。按照实体瘤疗效评价标准1.1版（Response Evaluation Criteriation in Solid Tumours, RECIST v1.1）评价客观疗效。按照不良反应通用术语标准4.0版（ Common Terminology Criteria for Adverse Events v4.0, CTC AE v4.0）评估用药期间发生的不良事件。结果该患者服用克唑替尼3个月后,肺部病变接近完全缓解（complete remission, CR）,颅内病变部分缓解（partial response, PR）,腹腔病变CR,视物模糊症状减轻。结论综合运用手术、全脑放疗+残留灶补量放疗、克唑替尼治疗ROS1融合基因阳性伴有症状脑转移的肺腺癌患者,可有效控制颅内颅外病灶,耐受性好。     

纳武单抗对晚期非小细胞肺癌的疗效和安全性的单中心分析

背景与目的：纳武单抗（nivolumab）是一种免疫检查点抑制剂,对T细胞表面的程序性死亡［蛋白］-1（programmed death-1,PD-1）具有高度亲和力,通过与其结合来恢复T细胞的抗肿瘤免疫反应。回顾性分析纳武单抗对于既往接受过含铂类药物方案化疗后疾病进展或不可耐受的局部晚期或转移性非小细胞肺癌（non-small cell lung cancer,NSCLC）患者的疗效和安全性。方法：收集上海市胸科医院2016年1月—2019年4月期间接受纳武单抗治疗的30例NSCLC患者,统计用药过程中发生的不良事件。治疗方法为按3 mg/kg的剂量静脉输注纳武单抗,每次输注60 min,每2周1次,直到出现疾病进展或不能接受的毒性。结果：所有不良事件按照常见不良事件评价标准（Common Terminology Criteria for Adverse Events,CTCAE）4.0版评估,30例患者中有25例至少报告了1个不良事件,出现的药物相关不良事件有疲劳、红疹、贫血等,其中以疲劳（50%）最常见。有3例患者出现3级药物相关不良事件：疲劳、贫血和总胆红素升高,没有出现4~5级不良事件以及治疗相关死亡事件。药物相关不良事件级别大多数较低（1~2级）,无需特殊处理,少数患者出现甲状腺功能亢进以及间质性肺炎等,予对症治疗后均好转。结论：纳武单抗用于二线治疗晚期NSCLC耐受性较好,具有较高的安全性。     

结合肺灌注影像参数的等效均匀剂量模型与放射性肺炎的相关性研究

背景与目的:目前,临床上用来预测放射性肺损伤的肺剂量体积参数准确度较低,且阈值不统一.该研究通过肺功能影像,探讨结合肺血流参数的等效均匀剂量(equivalent uniform dose,EUD)在预测放射性肺炎方面的价值.方法:将15例肺癌放疗患者肺灌注影像与定位CT影像形变融合,以肺灌注最高计数为归一点,将肺依功能状态分为四级区域,取每级区域中的平均计数与最高计数的比值作为肺灌注系数代入EUD模型中,获得肺部的功能等效均匀剂量(functional equivalent uniform dose,fEUD)模型.比较单肺及双肺的fEUD与不含肺功能指数的等效均匀剂量(general equivalent uniform dose,gEUD)、V5、V20在预测放射性肺炎方面的统计学差异,并进一步分析上述参数的统计学分布特征及彼此之间的相关性.放射性肺炎的判断标准采用不良事件常用术语评定标准(Common Terminology Criteria for Adverse Events,CTCAE)4.03版肺部症状3级以上,P<0.05为差异有统计学意义.结果:该研究的样本中,当V5、V20等指标显示与放射性肺炎无关时,高剂量侧肺的fEUD值呈现与放射性肺炎显著相关(P=0.007).单侧肺fEUD值与gEUD值呈显著线性关系(t=0.815,P=0.000).结论:单侧肺fEUD较传统剂量-体积指标更好地体现了肺功能不同区域间的放射生物学差异,可以作为放射性肺炎预测指标,建议阈值为21 Gy.     

培美曲塞致皮肤色素沉着与肺腺癌化疗疗效关系的研究

目的:探讨晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)中肺腺癌患者使用培美曲塞化疗出现色素沉着及其与临床病理特征、培美曲塞化疗疗效的相关性.方法:收集新疆医科大学附属肿瘤医院2016年1月至2018年12月经组织病理证实为肺腺癌患者117例,采用不良事件的通用术语标准(CTCAE...     

钙镁输液预防奥沙利铂神经毒性的作用:一个Ⅲ期试验(英文)

Objective:This study is a prospective randomized, double-blind, placebo-controlled study to evaluate the effect of calcium and magnesium (Ca/Mg) infusion on amelioration of oxaliplatin neuropathy, the dose-limiting toxicity. Methods:Sixty patients with resected colorectal carcinoma (CRC) planned to receive adjuvant oxaliplatin-containing regimen were randomly assigned to two arms; Arm A:patients received Ca/Mg were given as 1 gm Ca gluconate and 1 gm MgSO 4 in 250 mL of intravenous (IV) solution over 30 min pre and post oxaliplatin infusion, and Arm B:patients received 250 mL of IV solution without Ca/Mg over 30 min pre and post oxaliplatin infusion. Primary outcome was to assess percentage of patients with oxaliplatin-induced neurotoxicity. Neurotoxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0. Results:Sixty patients in both arms were assessed, 30 with Ca/Mg infusion and 30 without. Patients developed neurotoxicity in arm A were significantly lower than that in arm B after the end of treatment; 7 (23.3%) and 14 (46.6%) respectively (P < 0.05), and significantly lower duration of neuropathy in months (8 ± 2.5 vs 18 ± 3) respectively (P < 0.001). Conclusion:Use of IV Ca/Mg showed a statistically significant reduction of peripheral neuropathy (PN) in patients with CRC receiving oxaliplatin in the adjuvant settings.     

胸壁和区域淋巴引流区整体调强放疗在乳腺癌改良根治术后的应用研究北大核心

目的:评价胸壁和区域淋巴引流区整体调强放疗与分段三维适形放疗两种方法在乳腺癌改良根治术后患者中的疗效差异。方法:回顾性分析两种放疗模式在311例乳腺癌改良根治术患者中的疗效差异,采用Kaplan-Meier法计算无疾病生存(disease free survival,DFS)率及总体生存率(overall survival,OS),Cox回归分析影响预后的单因素及多因素。基于CTCAE 4.0(Common Toxicity Criteria for Adverse Events)准则评估两种放疗技术的晚期副反应差异。结果:纳入的311例患者中,有195例接受了整体调强放疗,116例接受传统三维适形放疗。整体调强放疗组和分段三维适形放疗组5年DFS分别为88.7%和78.8%(P=0.013),5年OS分别为93.8%和89.4%(P=0.280)。单因素分析显示,T、N分期、分化程度、内乳淋巴结照射及放疗方式是影响乳腺癌改良根治术后患者DFS的预后因素,T分期、分化程度是OS的预后因素。多因素分析显示,分化程度、内乳淋巴结照射及放疗方式是影响患者DFS的独立预后因素,分化程度、内乳淋巴结照射是影响患者OS的独立预后因素。两种放疗方式常见的晚期副反应无明显差异。结论:胸壁和区域淋巴引流区整体化调强放疗可降低乳腺癌改良根治术后患者的复发率,且毒副反应可耐受。     

Vorolanib,an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors:An open-label,phaseⅠdose escalation and dose expansion trial

Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received increasing doses of oral vorolanib(50-250 mg once daily)in cycles of four weeks for up to one year.During dose expansion,patients received recommended doses(100 and 200 mg)in 4-week cycles.The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose(RP2 D).The severity and type of adverse drug reactions(ADRs)were assessed using the Common Terminology Criteria for Adverse Events version 4.0.The second endpoint was preliminary efficacy in terms of objective response and progression-free survival(PFS).Results:No dose-limiting toxicity occurred during dose escalation(50-250 mg).Five(26.3%)patients in the escalation cohort(n=19)and 12(48.0%)in the expansion cohort(n=25)experienced grade 3 ADRs.The most common ADRs were hair color changes,fatigue,portal hypertension,hypertriglyceridemia,and proteinuria.During dose expansion,the patients treated with 200 mg and 100 mg(once daily)showed an objective response rate of 22.2%and 5.9%,respectively;the disease control rate was 88.9%and 73.3%,respectively;the median PFS was9.9[95%confidence interval(95%CI):7.4-not reached]months and 3.8(95%CI:1.9-not reached)months,respectively.Conclusions:Oral vorolanib at a dose of 200 mg(once daily)exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors.The RP2 D for vorolanib was determined to be 200 mg as a daily regimen.     

CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment

Multiple systems have been developed for grading the adverse effects (AEs) of cancer treatment. The National Cancer Institute Common Toxicity Criteria (CTC) system has substantially evolved since its inception in 1983. The most recent version, CTCAE v3.0 (Common Terminology Criteria for Adverse Events version 3.0) represents the first comprehensive, multimodality grading system for reporting the acute and late effects of cancer treatment. The new CTC requires changes in the application of AE criteria including new guidelines regarding late effects, surgical and pediatric effects, multimodality issues, and for reporting the duration of an effect. It builds on the strengths of previous systems, represents a considerable effort among hundreds of participants, and signifies an international collaboration and consensus of the oncology research community. This article updates recent progress in the evolution of adverse effects grading systems and reviews the development of CTCAE v3.0.     

Is there room for improvement in adverse event reporting in the era of targeted therapies?

The Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, and its predecessors, the Common Toxicity Criteria (CTC) versions 1.0 and 2.0, were developed under the direction of the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI) in an effort to provide standard language for reporting adverse events that occur in NCI-sponsored clinical trials. Each successive version of the CTC has improved the accuracy, precision, and completeness of the criteria in an effort to standardize reporting. We believe that the current version of the CTCAE cannot adequately code the subacute adverse events that commonly occur with today's targeted therapies.     

Grading-system-dependent volume effects for late radiation-induced rectal toxicity after curative radiotherapy for prostate cancer

PURPOSE: To assess the association between the dose distributions in the rectum and late Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer (RTOG/EORTC), Late Effects of Normal Tissue SOMA, and Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 graded rectal toxicity among patients with prostate cancer treated with RT. METHODS AND MATERIALS: Included in the study were 124 patients who received three-dimensional conformal RT for prostate cancer to a total dose of 70 Gy in 2-Gy fractions. All patients completed questionnaires regarding rectum complaints before RT and during long-term follow-up. Late rectum Grade 2 or worse toxicity, according to RTOG/EORTC, LENT SOMA, and CTCAE v3.0 criteria, was analyzed in relation to rectal dose and volume parameters. RESULTS: Dose-volume thresholds (V40>or=65%, V50>or=55%, V65>or=45%, V70>or=20%, and a rectum volumeor=70 Gy (V70) was most predictive for late Grade 2 or worse rectal toxicity with each of the grading systems. The associations were strongest, however, with use of the LENT SOMA system. CONCLUSIONS: Volume effects for late radiation-induced rectal toxicity are present, but their clinical significance depends on the grading system used. This should be taken into account in the interpretation of studies reporting on radiation-induced rectal toxicity.     

Rectal toxicity profile after transperineal interstitial permanent prostate brachytherapy: use of a comprehensive toxicity scoring system and identification of rectal dosimetric toxicity predictors

PURPOSE: To better understand rectal toxicity after prostate brachytherapy, we employed the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0), a comprehensive system with distinct and separately reported gastrointestinal adverse event items (unlike Radiation Therapy Oncology Group morbidity scoring), to evaluate item-specific postimplant rectal toxicities. METHODS AND MATERIALS: We analyzed 135 patients treated with brachytherapy +/- hormonal therapy, using CTCAE v3.0 to score acute/late rectal toxicities (median follow-up, 41 months). Dosimetric parameters were evaluated for ability to predict toxicities. RESULTS: Use of CTCAE yielded a novel rectal toxicity profile consisting of diarrhea, incontinence, urgency, proctitis, pain, spasms, and hemorrhage event rates. No item had a < 5% Grade 1-2 acute toxicity rate (except spasms). Rectal dosimetry predicted late toxicities: for diarrhea, 5% Grade 1 toxicity rate for %V25 (percent of rectal volume receiving 25% of prescribed prostate dose) < or = 25% vs. 60% for %V25 > 25% (p < 0.001); for maximum toxicity, 10% Grade 1 toxicity rate for %V10 < or = 40% vs. 44% for %V10 > 40% (p = 0.007). CONCLUSIONS: A comprehensive understanding of item-specific postimplant rectal toxicities was obtained using CTCAE. Rectal %V25 > 25% and %V10 > 40% predicted worse late diarrhea and maximum toxicity, respectively.     

Comparative survey on current status and the differences of treatment using modified FOLFOX6 regimen in patients with colorectal cancer in two general hospitals

We surveyed the current status and the differences of treatment of colorectal cancer using modified FOLFOX6 regimen, in two general hospitals, Sakai City Hospital (A hospital) and Takarazuka Municipal Hospital (B hospital) between April 2005 and November 2006, retrospectively. The numbers of examined patients were 33 and 17 in A and B hospitals, respectively. The grade of myelosuppression and peripheral neuropathy were evaluated according to Common Terminology Criteria for Adverse Events v 3.0(CTCAE v 3.0)and Neurotoxicity Criteria of DEBIOPHARM(DEB-NTC). The setting of dosage was differed in two hospitals. In A hospital, the dosages of oxaliplatin, 5-FU bolus and 5-FU continuous infusion were more than 90% of the standard one at first time, and were reduced with almost same degree in the appearance of adverse effects. On the other hand, in B hospital, the dosages of these drugs were reduced about 20% even at first administration and, especially, the dose of 5-FU bolus tended to be remarkable reduction. Of adverse events, the rates of the appearance of neutropenia more than grade 3 was 21.2% and 47.1%, in A and B hospitals, respectively. No difference in peripheral neuropathy was detected at both hospitals. In conclusion, the differences in these two hospitals were detected in the dosage setting and myelosuppression, not in non-hematological adverse effects.     

Effects of treatment intensification on acute local toxicity during radiotherapy for head and neck cancer: prospective observational study validating CTCAE, version 3.0, scoring system

PURPOSE: To quantify the incidence and severity of acute local toxicity in head and neck cancer patients treated with radiotherapy (RT), with or without chemotherapy (CHT), using the Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0), scoring system. METHODS AND MATERIALS: Between 2004 and 2006, 149 patients with head and neck cancer treated with RT at our center were prospectively evaluated for local toxicity during treatment. On a weekly basis, patients were monitored and eight toxicity items were recorded according to the CTCAE v3.0 scoring system. Of the 149 patients, 48 (32%) were treated with RT alone (conventional fractionation), 82 (55%) with concomitant CHT and conventional fractionation RT, and 20 (13%) with accelerated-fractionation RT and CHT. RESULTS: Severe (Grade 3-4) adverse events were recorded in 28% (mucositis), 33% (dysphagia), 40% (pain), and 12% (skin) of patients. Multivariate analysis showed CHT to be the most relevant factor independently predicting for worse toxicity (mucositis, dysphagia, weight loss, salivary changes). In contrast, previous surgery, RT acceleration and older age, female gender, and younger age, respectively, predicted for a worse outcome of mucositis, weight loss, pain, and dermatitis. The T-score method confirmed that conventional RT alone is in the "low-burden" class (T-score = 0.6) and suggests that concurrent CHT and conventional fractionation RT is in the "high-burden" class (T-score = 1.15). Combined CHT and accelerated-fractionation RT had the highest T-score at 1.9. CONCLUSIONS: The CTCAE v3.0 proved to be a reliable tool to quantify acute toxicity in head and neck cancer patients treated with various treatment intensities. The effect of CHT and RT acceleration on the acute toxicity burden was clinically relevant.     

Evaluating the Incidence Rate of an Accelerated Short Course High Dose Rate Intravaginal Brachytherapy Complications in Patients with Endometrial Cancer

Background: Brachytherapy in treatment of endometrial cancer patients is growing and therefore, evaluation ofmore feasible schedule has become of great importance. The purpose of current study was to evaluate the complicationsof accelerated short course high dose rate intravaginal brachytherapy (HDR IVB), a new brachytherapy approachwhich is a more feasible treatment option in developing countries. Method: From 2017 to 2018, 54 patients diagnosedwith endometrial cancer and FIGO stages IA to IIB who underwent total abdominal hysterectomy with a bilateralsalpingo-oophorectomy were enrolled in present study. They were treated with a total dose of 25 Gy in 5 fractionswhich was prescribed daily. A dose of 5 Gy was prescribed at a depth of 0.5 cm in the upper third and middle thirdof vagina. Adverse effects related to organs at risk consist of bladder, vagina and rectum were documented based onthe Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). Results: The accelerated short courseHDR IVB was well tolerated and no grade 3 or higher toxicities was reported for patients during the follow up period.There were no chronic rectal toxicities and only one patient showed chronic urinary toxicities. However, the incidencerate of vaginal toxicities at the end of 4-month and 8-month follow up periods was higher than acute toxicities andsignificantly lower in elderly group compared to younger group. Conclusion: Overall, the accelerated HDR IVB wassafe and was well tolerated in endometrial cancer patients and the incidence rate of undue complications were equal,if not less, in elderly patients compared to the younger ones.     

曲妥珠单抗联合内分泌维持治疗HR和HER-2阳性晚期乳腺癌的临床观察

目的 探讨曲妥珠单抗联合内分泌维持治疗激素受体（HR）和人表皮生长因子受体-2（HER-2）阳性复发转移性乳腺癌的疗效与安全性。方法 回顾性分析本院2013年1月至2016年1月收治的HR和HER-2阳性复发转移性乳腺癌患者31例,一线曲妥珠单抗联合化疗达到病情缓解或稳定后继续曲妥珠单抗联合内分泌维持治疗,采用RECIST 1.1版标准评估维持治疗的疗效,采用常见不良反应事件评价标准（CTCAE）4.0版评价毒性反应,根据随访资料分析预后。结果 31例复发转移性乳腺癌维持治疗的中位无进展生存期为12.0个月（95％CI：5.4～18.6个月）。5例患者在一线化疗后获完全缓解,无可评估病灶,其余26例可评估近期疗效,总有效率和临床获益率分别为26.9％和88.5％。内分泌联合曲妥珠单抗的主要不良反应较轻,主要包括乏力（19.4％）、潮热（16.1％）和恶心呕吐（9.7％）。结论 一线曲妥珠单抗联合化疗有效后,曲妥珠单抗联合内分泌维持治疗HR+／HER-2+转移性乳腺癌可进一步改善患者的临床获益,且安全性良好。     

Principles and practice of clinical phase II studies

Primary aim of the phase II study is to assess the antitumoral activity of new agents and in a second step their therapeutic effectivity. In addition, toxicity will be assessed. For cytotoxic agents, tumor shrinkage, the socalled response, is the dominant parameter for evaluation. Nowadays, the Response Evaluation Criteria in Solid Tumors (RECIST) are widely used. For cytostatic agents with preponderance of tumor growth inhibition, the time interval to tumor progression has been proven to be the more relevant parameter. In addition, further parameters of clinical benefit are to be tested. Whether or not a parameter can be used as surrogate for a relevant endpoint has to be validated for each of them separately. For the assessment of toxicity, the Common Terminology Criteria for Adverse Events (CTCAE; current version 3.0) are used. The early phase II study allows to assess cumulative toxicity, pharmacokinetics, and pharmacokinetic-pharmacodynamic interactions. The socalled late phase II study focuses on the assessment of the therapeutic effect of both single-agent therapy and combinations of drugs and/or therapeutic modalities. The phase II study continues to be of high impact, especially for the testing of substances with well-defined molecular targets to identify those which will consecutively yield positive phase III trials out of a plethora of substances.     

Evaluation of Bortezomib-Induced Neuropathy Using Total Neuropathy Score (Reduced and Clinical Versions) and NCI CTCAE v4.0 in Newly Diagnosed Patients With Multiple Myeloma Receiving Bortezomib-Based Induction

BackgroundBortezomib-induced peripheral neuropathy (BiPN) is a dose-limiting adverse effect of bortezomib-based therapy for multiple myeloma (MM). The reporting of BiPN is variable because of the use of different neuropathy scales. Most investigators use the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).Patients and MethodsWe prospectively evaluated the incidence of BiPN in treatment-naive patients with MM receiving weekly cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in 28-day cycles using 3 neuropathy scores: Total Neuropathy Score—reduced (TNSr) and —clinical (TNSc), and NCI CTCAE v4.0.ResultsTwenty-six patients received CyBorD. Twenty patients completed follow-up. The rates of occurrence of BiPN were as follows: TNSr - 55% (n = 11), TNSc - 40% (n = 8), and NCI CTCAE - 45% (n = 9). All 3 scales showed worsening after treatment (P < .01). When compared to BiPN by TNSr, sensitivities for NCI CTCAE and TNSc were 77.8% and 88.9%, respectively. Specificity was 63.3% for both NCI CTCAE and TNSc. Among 12 patients who did not have BiPN by NCI CTCAE scale, 41.7% (n = 5) and 16.7% (n = 2) patients satisfied the criteria for BiPN by TNSr and TNSc, respectively. The higher detection rate of neuropathy by TNSr and TNSc is probably due to increment in scores that are allotted for increase in anatomic extent of sensorimotor involvement, unlike the NCI CTCAE scale, which requires functional limitation for increase in grade.ConclusionNCI CTCAE may be suboptimal in comparison to TNSr and TNSc in assessment of BiPN because it may miss worsening neuropathy without functional limitation.