Safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience

We evaluated the safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer (NSCLC). We retrospectively compared toxicity, response and survival outcomes for gefitinib in patients aged 75 years or older (elderly group) with the same outcomes in patients aged younger than 75 years. In total, 350 patients were eligible for this analysis, of whom 92 were in the elderly group and 258 in the non-elderly group. In the elderly group, adverse events were generally mild to moderate and grade 3-4 adverse events were observed in 8 (9%) patients. The objective response rate (17 vs. 21% for elderly vs. non-elderly, respectively) and median survival time (7.6 vs. 9.3 months) were also similar in the two groups. Multivariate analysis revealed elderly patients with lower Brinkman index tended to be more sensitive to gefitinib (odds ratio: 4.57, 95% confidence interval: 0.91-22.72, p = 0.0642). In this study, treatment with gefitinib appeared to be as safe and effective in elderly patients (aged 75 or older) with NSCLC as in non-elderly patients.     

Continued gefitinib treatment after disease stabilisation prolongs survival of Japanese patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience.

BACKGROUND: This study aimed to investigate the survival outcome of patients with non-small-cell lung cancer (NSCLC) who had obtained disease stabilisation with gefitinib treatment and to clarify the effect of continued treatment with gefitinib on prognosis. PATIENTS AND METHODS: We reviewed the clinical records of 365 Japanese patients with NSCLC who received gefitinib (250 mg/day). RESULTS: Of 324 (89%) patients assessable for response, 147 (45%) obtained disease stabilisation and 71 (22%) patients achieved an objective response. Overall survival in patients obtaining disease stabilisation was significantly longer than in patients with progressive disease (median survival time 12.1 versus 4.4 months; P <0.0001). In patients obtaining disease stabilisation, those who continued gefitinib treatment until disease progression tended to have longer overall and progression-free survival compared with those discontinuing gefitinib treatment (1-year survival rate 52.1% versus 36.6%, P = 0.08; 1-year progression-free survival rate 31.8% versus 5.2%, P = 0.001). Multivariate analysis showed discontinuing gefitinib was an independent risk factor for progression-free survival (hazard ratio 1.66; 95% confidence interval 1.07-2.56; P = 0.022) but not for overall survival. CONCLUSIONS: Our findings indicate the importance of achieving disease stabilisation with gefitinib treatment and continued gefitinib treatment in Japanese patients with disease stabilisation, although further studies are required to confirm these findings.     

Erlotinib as salvage treatment after failure to first-line gefitinib in non-small cell lung cancer

Purpose

Chemotherapy is the mainstay treatment for advanced non-small cell lung cancer (NSCLC). Gefitinib, an epidermal growth factor receptor—tyrosine kinase inhibitor (EGFR-TKI), has been recently shown to be effective as a first-line treatment in Asian patients with advanced NSCLC, especially for those with favourable clinical features such as female, non-smoker and adenocarcinoma. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment. The purpose of this study is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib.

Method

Retrospective review of NSCLC patients with favourable clinical features who received gefitinib as first-line treatment and subsequent salvage treatment with erlotinib.

Results

A total of 21 patients with NSCLC were included in the study. Among them, 18 (85.7%) patients had disease control with gefitinib and 12 (57.1%) patients with salvage erlotinib. There was an association between the disease control with gefitinib and erlotinib (p = 0.031). The disease control rate of erlotinib was independent of the chemotherapy use between the two EGFR-TKIs.

Conclusion

For NSCLC patients with favourable clinical features, erlotinib was effective in those who had prior disease control with first-line gefitinib.     

AP化疗方案治疗EGFR-TKI一线化疗失败非小细胞肺癌患者的疗效及对预后的影响

目的探讨培美曲塞联合顺铂(AP)化疗方案二线治疗表皮生长因子受体-酪氨酸激酶抑制剂(EGFRTKI)一线治疗失败非小细胞肺癌(NSCLC)患者的疗效及对预后的影响。方法将90例经EGFR-TKI一线化疗失败的NSCLC患者根据随机数字表法分为AP组(培美曲塞联合顺铂)和GP组(吉西他滨联合顺铂),每组45例。比较两组患者化疗近期疗效、不良反应、生活质量及生存情况。结果AP组患者客观缓解率(ORR)与疾病控制率(DCR)均略高于GP组,但差异均无统计学意义(P>0.05)。AP组患者白细胞减少、中性粒细胞减少、血小板下降发生率均低于GP组,差异均有统计学意义(P<0.05)。化疗前,两组患者Karnofsky评分比较,差异均无统计学意义(P>0.05);化疗后,两组患者Karnofsky评分均升高,差异均有统计学意义(P<0.05)。两组生存情况比较,差异无统计学意义(P>0.05)。结论二线AP和GP化疗方案对EGFR-TKI一线治疗失败NSCLC患者近期疗效、生存时间和生活质量影响相似,但AP方案不良反应较少,更为安全。     

Pharmacoeconomic analysis of consolidation therapy with pemetrexed after first-line chemotherapy for non-small cell lung cancer

Prolongation of progression-free survival and overall survival have been reported with consolidation therapy after first-line chemotherapy in non-small cell lung cancer, but only a few pharmacoeconomic analyses have been performed. We performed a pharmacoeconomic analysis to assess the cost-effectiveness of consolidation therapy with pemetrexed compared with non-consolidation therapy. We developed a Markov model to evaluate the incremental cost-effectiveness ratio (ICER) of consolidation therapy with pemetrexed compared with non-consolidation therapy based on previous reports. We analyzed all histology groups together, and individually analyzed non-squamous cell carcinoma, in which pemetrexed has been shown to be more effective, and squamous cell carcinoma, in which pemetrexed has been shown to be less effective. We conducted a Monte-Carlo simulation to assess the uncertainty for our analysis model and the willingness to pay using thresholds. The ICER for consolidation therapy with pemetrexed was about US$ 109,024/life years gained (LYG) (JPY 12.5 million/LYG) and US$ 203,022/quality-adjusted life years (QALY) (JPY 23.3 million/QALY) for all histology. For non-squamous cell carcinoma, respective values were US$ 80,563/LYG (JPY 9.3 million/LYG) and US$ 150,115/QALY (JPY 17.3 million/QALY). Both % of probability at a threshold of JPY 5.0 million (US$ 43,478) for all histology and non-squamous cell carcinoma were less than 0.1%. This result indicates that it is difficult to use consolidation therapy as the standard of care in Japan while being covered by general medical insurance.     

晚期NSCLC一线化疗疾病控制与生存关系的分析

目的回顾性分析一线化疗疾病控制（DCR）与进展（PD）患者之间生存的差别,探讨DCR可否预测生存。方法本文回顾性分析本院一线含铂联合化疗86例ⅢB期/Ⅳ期非小细胞肺癌（NSCLC）患者,化疗的疗效按WHO标准分为CR,PR,SD,PD。结果一线化疗后DCR共64例（74.4%）[其中CR 0例,PR 30例（34.9%）,SD 34例（39.5%）],PD 22例（25.6%）。DCR和PD患者中位生存期（MST）有统计学意义,为14.2月和5.1月（P〈0.001）。CR＋PR和SD患者MST有统计学意义,为15.0月和11.0月（P=0.030）。COX多因素回归分析显示一线化疗疾病控制（P=0.017）,ECOG评分（P=0.046）是总生存的独立预后因素。结论本研究提示晚期NSCLC患者一线化疗疾病控制患者其生存较进展患者好,疾病控制比化疗有效似乎更能反映化疗疗效,预测生存期。     

Patterns of failure in combined chemotherapy and radiotherapy for limited small cell lung cancer: Southeastern Cancer Study Group experience

In this analysis, we compare the patterns of failure in the first 12 months for 660 eligible patients randomized to two Southeastern Cancer Study Group (SECSG) protocols for limited extent, small cell carcinoma of the lung between 1978 and 1985. In each protocol, a different schedule of radiotherapy was given in conjunction with combination chemotherapy and was compared with combination chemotherapy alone. In protocol 78 LUN 328, radiotherapy was given between courses of chemotherapy, and in protocol LUN 81343, it was given simultaneously. The rates of local failure, either as an initial or subsequent site, in the first 12 months were significantly lower when thoracic irradiation was given than when it was not (P less than .01). When the 2 radiotherapy arms were compared, there were no significant differences in the rates of local failure alone, but a smaller proportion of patients developed both local failure and distant metastases (P less than .01) when simultaneous radiotherapy was administered. Survival on all 4 arms was similar during the first 2 years of patient study. After 2 years, both radiotherapy regimens showed a trend toward improved survival compared with the combination drug alone (cyclophosphamide, doxorubicin, vincristine) arms. On both protocols, survival from 12 months was significantly longer for those with local control at 12 months than for those who did not show local control.     

安罗替尼对比多西他赛用于一线治疗失败后晚期非小细胞肺癌的疗效及安全性研究

目的 评价安罗替尼对比多西他赛用于一线治疗失败的晚期非小细胞肺癌(NSCLC)的疗效及安全性,探讨安罗替尼用于二线治疗晚期NSCLC的可行性.方法 收集2018年1月至2020年3月云南省肿瘤医院干部医疗科收治的60例晚期NSCLC患者,根据临床治疗方案不同均分为3组:安罗替尼组、多西他赛组及联合组,安罗替尼组口服安罗...     

比较吉非替尼与化疗一线治疗晚期非小细胞肺癌的Meta分析

目的 评价吉非替尼对比以铂类为基础的联合化疗一线治疗晚期非小细胞肺癌（NSCLC）的疗效与安全性。方法 检索PubMed、EMbase、中国生物医学文献数据库和中国知网等数据库,纳入吉非替尼对比铂类联合第3代化疗药物一线治疗晚期NSCLC的随机对照研究,检索时间截止于2012年3月,采用Stata 10.0软件进行Meta分析。结果 最终纳入4项研究,共1926例患者。在表皮生长因子受体（EGFR）突变阳性的人群中,吉非替尼在无进展生存期（HR=0.43,95％CI：0.32～0.58,P＜0.001）和有效率（71.5％ vs.38.1％,OR=4.04,95％CI：2.90～5.61,P＜0.001）方面均优于化疗组,在总生存期方面两组差异无统计学意义（HR=0.93,95％CI：0.75～1.15,P=0.492）。在安全性方面,吉非替尼主要为皮疹、腹泻和肝功能损害;化疗为中性粒细胞减少、血小板减少和贫血。结论 吉非替尼一线治疗晚期NSCLC具有一定优势,可作为EGFR敏感突变者的一线用药选择。     

晚期非小细胞肺癌一线治疗新进展

目的:总结近期晚期非小细胞肺癌一线治疗最新进展.方法:应用Medline和CKNI期刊全文数据库系统,以"晚期非小细胞肺癌、一线治疗、靶向治疗和维持治疗"为关键词,搜索近期发表的大型临床研究,选择以Ⅲ期研究为主的大型多中心随机临床研究.共计纳入文献29篇.结果:随着多项新药临床试验的完成,一线治疗方案和治疗理念有了新的突破--含铂两药化疗模式不再是唯一的一线治疗方法,化疗联合靶向、靶向单药正逐步成为一线治疗的选择.同时,非小细胞肺癌根据不同亚型选择不同的治疗已成为必然趋势.而通过基因突变筛选患者接受靶向治疗不仅提高了治疗的有效率,也避免了不必要的过度治疗.另外维持治疗概念的引入也成为一线治疗疗程模式的一大突破.结论:目前公认的晚期非小细胞肺癌一线治疗标准是含铂的两药联合方案.随着多项新药临床试验的完成,一线治疗方案和治疗理念有了新的突破.     

Short-term low-volume hydration in cisplatin-based chemotherapy for patients with lung cancer: the second prospective feasibility study in the Okayama Lung Cancer Study Group Trial 1201

Objective

We previously reported the feasibility of short-term low-volume hydration in patients with advanced lung cancer who received cisplatin-based chemotherapy (Jpn J Clin Oncol 2013). We sought to determine the clinical usefulness of a more convenient hydration method, evaluating the safety and efficacy of shorter-term and lower-volume hydration.

Method

Chemonaïve patients with advanced lung cancer who were ≤75 years and reserved an adequate renal function for cisplatin use (≥60 mg/m²) were eligible. An intravenously administered hydration of 1700 ml in ~3.5 h with 1500 ml of orally administered hydration was investigated. The primary endpoint was the proportion of patients without grade 2 or worse renal toxicity in the first cycle.

Results

A total of 45 patients were registered, all of whom were evaluable for renal toxicity. The median baseline creatinine score was 0.70 mg/dl, and the median cisplatin dose on day 1 was 75 mg/m². In the first cycle, one patient (2 %) developed grade 2 creatinine toxicity, and thus, the proportion of patients with less than grade 2 was 98 % (the lower limit of 95 % confidence interval; 93 %), which met the primary endpoint. Five patients (11 %) had grade 1 or greater nephrotoxicity, three of whom successfully recovered. The objective response rate was 24 % and median progression-free survival 5.8 months.

Conclusion

This prospective study demonstrated the safety and efficacy of shorter-term lower-volume hydration.