Invasive mediastinal staging of non-small-cell lung cancer: a clinical practice guideline

Introduction

In non-small-cell lung cancer (nsclc), invasive mediastinal staging is typically used to guide treatment decision-making. Here, we present clinical practice guideline recommendations for invasive mediastinal staging in nsclc patients who have been staged T1–4, N0–3, with no distant metastases.

Methods

Draft recommendations were formulated based on the best available evidence gathered by a systematic review and a consensus of expert opinion. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline.

Results

In general, most clinical experts agreed with the guideline, approving it for methodologic rigour. More than 80% of the surveyed practitioners gave it a high quality rating. The expert reviewers also provided written comments, with some of the suggested changes being incorporated into the final version of the guideline.

Conclusions

In the clinical practice guideline, invasive mediastinal staging of nsclc is recommended in all cases except those involving patients with normal-sized lymph nodes, negative combine positron-emission tomography and computed tomography, and peripheral clinical stage 1A tumour. When performing mediastinoscopy, 5 nodal stations (2R/L, 4R/L, and 7) should routinely be examined.     

Erlotinib in advanced non-small-cell lung cancer after gefitinib failure

Purpose  To evaluate the efficacy and safety of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib treatment. Patients and methods  Patients with advanced or metastatic NSCLC, who had progressed after gefitinib treatment, were included in this study; patients received erlotinib 150 mg/day until disease progression or intolerable toxicity. Results  Twenty-one patients were included in this study. Among them, 14 (66.7%) were male and 7 (33.3%) were female; median age was 63 years; 10 (47.6%) patients were smokers; 9 (42.9%)patients had squamous cell carcinoma subtype; 8 (38.1%) patients had adenocarcinoma subtype and 4 (19%) patients had the other NSCLC subtype. Out of 21 patients, 2 (9.5%) had PR and 4 (19.0%) had SD, giving an overall response rate of 9.5% and a disease control rate of 28.5%. The median TTP were 55 days, the median OS were 135 days. Two patients with PR to erlotinib treatment were female never smokers with adenocarcinoma histology and both had partial response to prior gefitinib treatment. Three of four patients with a SD to erlotinib treatment also had SD from prior gefitinib therapy. Smoking history, histology and response to erlotinib were significantly correlated with survival. The most common toxic effects were skin rash. Conclusions  Erlotinib may be an option for a more highly selected subset of patients, especially those who had already benefited from prior gefitinib treatment.     

吉非替尼单药治疗晚期非小细胞肺癌

目的观察吉非替尼单药治疗晚期非小细胞肺癌（NSCLC）的疗效和不良反应。方法对50例晚期NSCLC患者给予吉非替尼250mg／d口服治疗,观察疗效和不良反应,采用欧洲癌症研究和治疗组织生活质量调查核心问卷QLQ-C30和简明乏力量表（BFI）对患者的生活质量及临床症状的改善进行评价,观察疾病进展时间（TTP）和中位生存时间（MST）。结果50例晚期NSCLC患者中,无完全缓解者,部分缓解（PR）8例（16．0％）,临床获益率为60．0％,临床获益率与性别、病理类型及吸烟史有关。到随访截止日期,50例患者中,20例（40．0％）存活,其MST为13个月;30例死亡患者TTP为5个月,MST为6个月。PR患者MST为9个月。综合生活质量改善率为58．0％,乏力症状缓解率为52．6％,出现症状缓解的中位时间为15d。不良反应主要为Ⅰ、Ⅱ度皮疹和腹泻,对症处理后可缓解。3例既往因放疗而引起放射性肺炎的患者中,2例放射性肺炎加重。结论吉非替尼有明显抗肿瘤作用,能明显提高晚期NSCLC患者的生活质量,改善临床症状,不良反应可以耐受。     

Carboplatin and vinorelbine in advanced non-small-cell lung cancer

 A total of 32 patients with advanced non-small-cell lung cancer were treated with carboplatin (350 mg/m², day 1) and vinorelbine (days 1 and 8) every 28 days. A response rate of 28% (95% confidence limits 12.5 – 43.7%) was observed. The activity of this combination was demonstrated in an outpatient setting with acceptable toxicity. Received: 6 July 1995 / Accepted: 19 October 1995     

长春瑞滨联合卡铂治疗老年晚期非小细胞肺癌

目的：观察长春瑞滨(诺维本，NVB)联合卡铂化疗方案治疗老年晚期非小细胞肺癌患的临床疗效及不良反应。方法：对住院治疗的25例老年晚期非小细胞肺癌患采用NVB联合卡铂化疗方案，NVB25mg／m^2第1、8天，卡铂350mg／m^2第1天。每4周重复，至少治疗两周期，按标准评价疗效和毒副反应。结果：可评价患25例，有效率为48％，中位生存期7个月，1年生存率为32％。主要毒性反应为骨髓抑制、消化道反应及静脉炎，多数为Ⅰ～Ⅲ度反应。结论：NVB联合卡铂方案治疗老年晚期非小细胞肺癌临床疗效较好，毒性反应可以耐受。     

长春瑞滨加奥沙利铂治疗晚期非小细胞肺癌的临床研究

目的：评价长春瑞滨加奥沙利铂的两联化疗治疗晚期非小细胞肺癌的疗效和毒副反应。方法：长春瑞滨25mg／m^2 iv d1、8，奥沙利铂130mg／m^2 iv d2，3周重复。结果：全组25例，共完成81个周期平均3个周期(2～6个周期)，PR9例，客观有效率36％(9／25)，中位生存期8个月(4～18个月)，1年生存率20％(5／25)，主要毒副反应为骨髓抑制、消化道反应、静脉炎。结论：长春瑞滨加奥沙利铂的两联化疗在晚期非小细胞肺癌中有较好疗效，毒性可以耐受。     

吉非替尼治疗男性晚期非小细胞肺癌59例报告

目的探讨吉非替尼单药治疗男性晚期非小细胞肺癌(NSCLC)的疗效及安全性。方法男性NSCLCⅣ期患者59例,其中腺癌、细支气管肺泡癌占86.4%,既往化疗2个方案以上者占66.1%。口服吉非替尼至病情进展或出现不可耐受不良反应。患者分别于治疗1个月、治疗3个月、治疗3个月以后每隔2个月复查。结果59例患者均可评价疗效,无完全缓解患者,部分缓解14例,稳定10例,进展35例,有效率为23.7%,稳定率为16.9%,疾病控制率为40.7%。中位肿瘤进展时间为1.8个月。中位生存时间为8.5个月,生存时间与最佳疗效及一般状况有关。1、2和3年生存率分别为42.4%、17.1%和13.3%。常见不良反应为皮肤改变和腹泻,多为1、2度。结论吉非替尼单药治疗男性晚期NSCLC疗效明确,疾病控制后患者生存时间延长,不良反应较易耐受,是二线、三线用药的良好选择。     

Survival and treatment patterns in elderly patients with advanced non-small-cell lung cancer in Manitoba

Lung cancer is the leading cause of cancer death worldwide. Non-small-cell lung cancer (nsclc) is the most common form of lung cancer, with a median age at diagnosis of 70 years. These elderly patients are often underrepresented in the randomized clinical trials upon which chemotherapy plans are based. The objective of the present study was to determine the patterns of treatment and survival in elderly patients with advanced nsclc in Manitoba.An eligible cohort of elderly patients over 70 years of age at diagnosis (n = 497) with advanced nsclc was identified from the provincial cancer registry database for the period 2001-2004. Of the 497 patients identified, only 147 had been evaluated by a medical oncologist, and 82 of the 147 had received chemotherapy treatment, which is 16.5% of the initial cohort.Patients who received chemotherapy were younger than those who did not receive chemotherapy. Most patients receiving chemotherapy (84%) received doublet chemotherapy, with an almost equal split between cisplatin and carboplatin treatment. The median survival times for patients in this cohort were 64 weeks (stage iii nsclc) and 56 weeks (stage iv) with chemotherapy treatment, and 46 weeks (stage iii) and 26 weeks (stage iv) without chemotherapy.Although 50% of patients with advanced nsclc are more than 70 years of age, few are evaluated by a medical oncologist and even fewer are treated with chemotherapy. However, it should be noted that, in the elderly patients who were treated, survival times are comparable to those experienced by younger patients, which is indicative of a benefit of chemotherapy treatment for those elderly patients.     

Response to chemotherapy has predictive value for further survival of patients with advanced non-small cell lung cancer: 10 years experience of the european lung cancer working party

The aim of this study was the assessment of the predictive value for survival of an antitumoral response to three courses of chemotherapy in association with various pretreatment characteristics in patients with non-resectable non-small cell lung cancer treated by cisplatin- (or carboplatin)-based combination regimens. Patients considered for this study were eligible patients with advanced non-small cell lung cancer registered in one of the seven trials conducted by the European Lung Cancer Working Party from December 1980 to August 1991. All these trials tested chemotherapy regimens with platinum derivatives (cisplatin and/or carboplatin). In this population of 1052 eligible patients, 752 were assessed in this analysis. Data were prospectively collected on 23 pretherapeutic variables and objective response after three chemotherapy cycles. The predictive value of response to chemotherapy on survival (measured from the time of response assessment i.e. 12 weeks after registration in the trial) was studied by univariate analysis as well as by multivariate methods (adjustment of the impact of several covariates simultaneously on the dependent variable) with adjustment for the pretreatment prognostic variables. After three cycles of chemotherapy, the global estimated median survival time was 24 weeks with a 95% confidence interval of 22–25 weeks. By univariate analysis, we identified an objective response to chemotherapy as a highly significant discriminant marker (P < 0.0001) for further survival with estimated median survival times of 41 weeks (95% CI: 38–46) and 19 weeks (95% CI: 17–20), respectively, for the responding and non-responding patients. In a Cox regression model fitted to the data using a forward stepwise procedure, this variable was the first selected explanatory variable. Its effect was adjusted by the introduction in the model of initial disease extent, Karnofsky performance status, serum calcium level and white blood cell count. These results were consistent with those obtained by application of recursive partitioning and amalgamation algorithms (RECPAM) which led to a classification of the patients into three homogeneous subgroups. Our results, using a classical Cox regression model consistent with those highlighted by application of a RECPAM analysis, found an objective response to chemotherapy to be a predominant predictive factor for further survival, although it did not allow any conclusion about a causal relationship. The RECPAM results led to a classification of the patients into three subgroups which needs to be validated in other series.     

老年晚期非小细胞肺癌一线治疗

非小细胞肺癌(non-small-cell lung cancer,NSCLC)是发病率和死亡率很高的恶性肿瘤之一。随着肿瘤精准治疗快速发展,针对NSCLC的治疗手段也层出不穷。老年患者在NSCLC患者中所占比例最高,如何针对老年患者群体制定合理治疗方案非常重要。本文结合NSCLC治疗传统手段与最新进展,从驱动基因阳性和驱动基因阴性两个方面展开讨论,总结老年晚期NSCLC一线治疗的基本策略,以期为临床治疗提供参考。     

长春瑞滨和卡铂联合同步放疗治疗晚期非小细胞肺癌观察

目的：评价国产长春瑞滨(盖诺)和卡铂联合同步放疗治疗晚期非小细胞肺癌的疗效及毒副反应。方法：106例Ⅲ期NSCLC患，分为二组，化放组在放疗的同时及放疗后进行4周期化疗，化疗用药盖诺25mg／m^2在每个周期的第1、8天静脉滴注给予；卡铂300mg／m^2第1天静脉滴注。单放组行单纯放疗。结果：化放组有效率71．4％，单放组有效率为42．0％。化放组的有效率明显高于单放组(P=0．008)。化放组和单放组的1、2年生存率分别为77．39％、30．33％和58．65％、15．75％，中位生存时间分别为18个月和13个月，其差异有显性(P=0．0407)。结论：盖诺和卡铂联合同步放疗是治疗晚期非小细胞肺癌的安全有效的治疗方法，值得进一步临床研究。     

A phase II study of weekly paclitaxel and carboplatin in previously untreated patients with advanced non-small-cell lung cancer

Purpose: Both paclitaxel (P) and carboplatin (C) have a significant activity in non-small cell lung cancer (NSCLC). Weekly administration of P is active, is dose intense, and has a favorable toxicity profile. To evaluate the efficacy and toxicity of weekly P and C in advanced-stage NSCLC, we initiated this phase II study in patients with advanced NSCLC (III B with pleural effusion and stage IV). Patients and Methods: Eligible patients were treated with paclitaxel 100 mg/m² intravenously (iv) over 1 h followed by carboplatin AUC 2 iv over 30 min. This treatment was administered weekly for 3 of every 4 wk until disease progression or intolerable toxicities. Results: Of the 30 patients enrolled in the study, one patient did not meet the eligibility criteria. Of the remaining 29 patients, 6 did not complete at least two cycles of treatment and hence were not assessable for response. The overall response rate was 43.5% (10/23) (all partial responses). An additional 43.5% had stable disease. The median time to progression was 162 d and the median duration of response was 169 d. Overall survival at 1 yr on intent-to-treat analyses was 44% and median survival was 10.8 mo. We observed the following grade 3/4 toxicities: hypersensitivity to paclitaxel (13%), hypersensitivity to carboplatin (3%), neutropenia (31%), thrombocytopenia (7%); 31% experienced grade 1 neuropathy and 17% experienced grade 2 neuropathy. Conclusions: We conclude that weekly paclitaxel and carboplatin is active and very well tolerated in patients with advanced NSCLC.     

Front-line paclitaxel and topotecan chemotherapy in advanced or metastatic non-small-cell lung cancer: a phase II trial

Purpose: Based on previous experience, we combined topotecan with paclitaxel (weekly administration) in patients with non-small-cell lung cancer (NSCLC). Our primary objective was to determine the response rate and survival and our secondary objective, the safety of the regimen. Methods: From October 2003, until March 2005, 45 patients all with histologically or cytologically confirmed NSCLC were enrolled. All patients were chemotherapy and radiotherapy naive. Both agents were infused on day 1 of every week once for three consecutive weeks, every 28 days. Three infusions were considered as one course. The treatment plan was to give three courses (nine infusions) and then to evaluate the response. Topotecan (1.75 mg/m²) was infused for 30 min and paclitaxel (70 mg/m²) for 90 min; these doses had been established as the maximum tolerated dose in a previous phase I–II trial. Results: Eighteen/45 (40%) patients responded, 2 (4.4%) complete responses and 16 (35.6%) partial responses. Twenty-one (46.7%) patients had stable disease, and 6 (13.3%) disease progression. The median duration of response was 8 months and median time to tumor progression 9 months. Grade 3 and 4 neutropenia was observed in two patients (in these two patients, the dose of both drugs was reduced by 25% and G-CSF was given), grade 4 thrombocytopenia in one patient and grade 4 anemia in one patient. Conclusion: This novel combination of topotecan–paclitaxel in a weekly administration rendered a 40% response rate, with very low toxicity in stages IIIA, IIIB and IV NSCLC patients.     

国产长春瑞滨软胶囊的Ⅱ期临床研究

目的：观察和评价国产长春瑞滨软胶囊联合顺铂治疗Ⅲ～Ⅳ期非小细胞肺癌的安全性和有效性。方法：本试验采用随机对照试验设计，随机将人组的48例非小细胞肺癌分为二组。联合试验组(A)：长春瑞滨软胶囊，60mg／m^2，1次服用，d1、d8；顺铂(PDD)，80mg／m^2，d1，每3周重复。联合对照组(B)：注射试用长春瑞滨，25mg／m^2 d1、d8；PDD，80mg／m^2 d1，每3周重复。两组止吐方案相同。结果：两组均无CR病例；试验组(A组)有效率为22．73％(5／22)，对照组的有效率为29．17％(7／24)。两组有效率比较差异无显性(P=0．742)。毒副反应：联合试验组主要不良反应为恶心、呕吐及骨髓抑制。其它毒副反应少见。结论：重酒石酸长春瑞滨软胶囊联合PDD治疗中晚期非小细胞肺癌与重酒石酸长春瑞滨注射剂(盖诺)联合DDP对比，疗效相当，毒副反应相仿，建议扩大验证且延长观察期进一步观察。     

吉西他滨联合顺铂双周方案与三周方案治疗晚期非小细胞肺癌的对比研究

目的研究对比吉西他滨(泽菲)联合顺铂双周方案与三周方案治疗晚期非小细胞肺癌的疗效及不良反应。方法双周方案组35例晚期非小细胞肺癌患者,给予吉西他滨1250mg/m2,d1,顺铂60mg/m2,d1,每14天重复,至少用4周期以上评价疗效。三周方案组32例患者,给予吉西他滨1000mg/m2,d1、d8,顺铂50mg/m2,d1、d2,每21天重复1次,至少用2周期以上评价疗效。结果67例均可评价疗效,双周方案组有效率48.6%(17/35),中位生存时间34.1周,1年生存率34.3%(12/35);三周方案组有效率43.7%(14/32),中位生存时间33.3周,1年生存率34.4%(11/32)。毒副反应方面,Ⅲ-Ⅳ度白细胞下降、Ⅲ-Ⅳ度血小板下降、Ⅲ-Ⅳ度恶心呕吐在双周方案组分别为8.6%、14.3%和5.7%,三周方案组分别为15.6%、18.8%和15.6%。结论吉西他滨(泽菲)联合顺铂双周方案与三周方案治疗非小细胞肺癌的疗效大致相等,双周方案不良反应明显减少。     

Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy

Objectives

Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT₃) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy.

Methods

Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT₃ receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy.

Results

A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2–88.1%) and 67.2% (95% CI, 55.3–77.2%; odds ratio (OR), 0.50; 95% CI, 0.22–1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08–0.70; p < 0.01) and the delayed phase (86.5% in the aprepitant group and 59.1% in the control group; OR, 0.23; 95% CI, 0.07–0.65; p < 0.01).

Conclusion

Carboplatin-based chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT₃ receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.     

Phase II study of the combination of vinorelbine and cisplatin in advanced non-small-cell lung cancer

Purpose To evaluate the efficacy and safety of combination chemotherapy with cisplatin and vinorelbine for the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods Eligible patients were those with measurable NSCLC. They were treated with two or more cycles of a regimen consisting of vinorelbine 25 mg/m² on days 1 and 8 and cisplatin 80 mg/m² on day 1 every 3 weeks.Results A total of 45 patients were enrolled. The response rate was 51.1% (23/45; 95% CI 35.8% to 66.3%). The median survival was 286 days with a 1-year survival rate of 40%. The median number of treatment cycles was 2. The major toxic effect was neutropenia of grade 3 or higher (84%). Nonhematological toxicities, including vomiting (62%), were mild (grade 2 or less). There were no treatment-related deaths.Conclusion The high response rate and good tolerability proved this combination therapy to be a safe and effective treatment for advanced NSCLC.This work was supported in part by a grant-in-aid from the Ministry of Health and Welfare (Tokyo, Japan) and from the Second Term Comprehensive 10-Year Strategy for Cancer Control.     

Docetaxel-induced interstitial pneumonitis following non-small-cell lung cancer treatment

Interstitial pneumonitis has been described infrequently following administration of docetaxel, used alone or in combination with other chemotherapeutic agents or concurrent irradiation, for non-small-cell lung cancer (NSCLC). This toxicity is of special relevance in NSCLC, as clinical severity and differential diagnosis may be especially challenging. It seems to be due to type I and type IV hypersensitivity reactions to the drug. Clinical and radiographic features are nonspecific and diagnosis is made by exclusion. The rate of grade III-IV docetaxel-induced pneumonitis, ranging from 7 to 47%, depends on several factors, including total dose, chemotherapy schedule and especially concomitant docetaxel treatment with gemcitabine and radiotherapy. Although the usual outcome is cure, it sometimes eventually progresses to pulmonary fibrosis despite steroid treatment. This toxicity must be taken into account when planning treatment strategies for NSCLC in order to reduce its rate and to achieve prompt diagnosis and treatment.     

吉西他滨治疗晚期非小细胞肺癌的现状

吉西他滨是近年来治疗晚期非小细胞肺癌的有效新药。国外大量临床试验已经证实其单一用药有效率稳定在20%以上,中位生存34周,可明显改善肿瘤相关症状,毒性易耐受,本文综述吉西他滨治疗晚期非小细胞肺癌的临床结果。     

GP方案与NP方案治疗非小细胞肺癌疗效及药物经济学评价

  目的 比较吉西他滨加顺铂（GP方案）与长春瑞滨加顺铂（NP方案）两种联合方案治疗晚期非小细胞肺癌（NSCLC）的疗效、毒副反应及药物经济学评价。方法 用GP方案治疗晚期NSCLC 39例（GP组）与NP方案治疗晚期NSCLC 37例（NP组），统计分析临床资料。结果 GP组有效率48.7 %，NP组有效率45.9 %，两组疗效差异无统计学意义（P＞0.05），毒副反应主要为恶心呕吐、骨髓抑制。NP组的静脉炎较GP组多发，GP组血小板减少及皮疹发生率高于NP组，GP组的疾病进展时间较NP组延长（P＜0.05）。2疗程平均药物费用GP组￥（23 664±384.7）元，NP组￥（8519.94±369.1）元，有效率与所需费用之比GP组￥（485.02±34.65）元，NP组￥（185.62±23.77）元，中位生存期与所需费用之比GP组￥（2211.59±59.15）元，NP组￥（946.66±43.3）元，1年生存率与所需费用之比GP组￥（608.33±14.35）元，NP组￥（243.43±21.57）元。药物费用NP组明显低于GP组，费用疗效比NP组优于GP组（P＜0.05）。结论 两种方案均为治疗晚期NSCLC的一线方案，在治疗晚期NSCLC时可选用。