Biweekly administration of docetaxel and vinorelbine as second-line chemotherapy for patients with stage IIIB and IV non-small cell lung cancer: a phase II study of the Galician Lung Cancer Group (GGCP 013-02)

The current report aims to evaluate the efficacy and safety profile of a biweekly administration of docetaxel and vinorelbine to patients with advanced non-small cell lung cancer, who had previously been treated for this disease. In a prospective, multicenter, open-label, phase II trial, patients received 40 mg/m of docetaxel and 20 mg/m of vinorelbine on days 1 and 15, every 28 days. Treatment continued for up to a maximum of six cycles, unless disease progression or unacceptable toxicity occurred, or consent was withdrawn. Fifty patients were enrolled in the study and they received 174 cycles of chemotherapy, with a median of three cycles per patient. All patients were evaluated for efficacy and toxicity in an intention-to-treat analysis. The overall response rate was 10% [95% confidence interval (CI): 1-19], including one complete response (2%) and four partial responses (8%). Previous chemotherapy of 80% of the responders included paclitaxel. Median time to disease progression was 2.7 months (95% CI: 2.2-4.3) and median overall survival was 6.5 months (95% CI: 2.5-9.2). The survival rates at 1 and 2 years were 18% (95% CI: 7-29) and 4% (95% CI: 0-10), respectively. The most frequent severe toxicities were neutropenia (20% of patients) and leukopenia (8% of patients). Other toxicities appeared in 4% or fewer of the patients. Biweekly administration of docetaxel and vinorelbine is feasible as a second-line treatment for non-small cell lung cancer patients, but its level of activity and toxicity does not suggest any advantage compared with the results obtained with single-agent docetaxel in the same setting.     

非鳞非小细胞肺癌患者二线化疗方案的成本-效果分析（英文）

肺癌是全球发病率最高的一类癌症,也是癌症相关死亡的最主要原因。这项研究分析了吉西他滨、培美曲塞和多西他赛用于中国晚期非鳞状非小细胞肺癌患者二线化疗的成本效果性。本研究建立了三状态的Markov模型,包括无进展生存状态、进展生存状态和死亡状态,以模拟非鳞非小细胞肺癌6年的疾病转归。采用敏感性分析评估模型的稳定性。模型基线分析结果显示,以中国2018年的3倍人均国民生产总值($29 383)为意愿支付阈值时,吉西他滨、培美曲塞和多西他赛用于非鳞非小细胞肺癌二线化疗方案患者所获得的质量调整生命年分别为0.233年、0.417年和0.272年,相应的总费用为5321.02美元、12143.94美元和9479.42美元。相较于吉西他滨,培美曲塞和多西他赛每增加一个质量调整生命年,相应的增量成本效果比将增加37 081.09美元和106 625.64美元,均超过了意愿支付阈值。一元敏感性分析表明,吉西他滨在疾病进展状态的效用值是对模型影响最大的参数。     

培美曲塞二线治疗晚期非小细胞肺癌的临床观察

目的观察培美曲塞二线治疗晚期非小细胞肺癌的疗效及毒副反应。方法我院2008年4月～2009年10月收治晚期NSCLC患者20例,均经病理组织学或细胞学确诊ⅢB期5例,Ⅳ期15例。均接受过2个周期以上的含铂方案化疗,肿瘤进展或复发,国产培美曲塞二钠500mg/m2D1,IV,每21天为1周期。持续用药直至肿瘤进展或出现不可耐受的不良反应。结果ORR为22.2%,DCR为75.0%,中位PFS为6个月,中位OS为10个月。全组患者临床症状均有不同程度的改善,主要表现为咳嗽、胸痛好转,胸闷、气促、乏力减轻和体力状态改善。主要不良反应有骨髓抑制、神经系统毒性、肝肾功能影响、皮疹、脱屑、皮肤搔痒、胃肠道反应如恶心、呕吐、腹泻、疲劳。不良反应主要为Ⅰ、Ⅱ级,无1例患者因出现不可耐受的不良反应而退出治疗,亦未出现药物相关死亡。结论PFS和OS不低于一线含铂化疗方案,中位总生存期甚至高于一线含铂化疗方案,且主要毒副反应耐受性较好,且可作为晚期非小细胞肺癌二线治疗首选。     

多西他赛联合卡铂一线治疗晚期非小细胞肺癌的临床观察

目的观察多西他赛(docetaxel)联用卡铂(carboplatin)对晚期非小细胞肺癌一线治疗的疗效和毒性反应。方法晚期非小细胞肺癌患者共31例,多西他赛用量75 mg/m2,第1天静脉滴注,卡铂AUC=5 mg.mL-1.min-1,第1天静脉滴注。21~28 d为1个疗程,每例患者至少接受2个疗程治疗。结果31例患者均可评价疗效,无完全缓解病例(CR),11例获部分缓解(PR),16例稳定(SD),4例疾病进展(PD),总有效率为35.5%(11/31),其中位疾病进展时间为4.5个月,中位生存时间10.2个月(3~20个月),1年生存率为45.1%,毒性反应主要有骨髓抑制、恶心、呕吐和腹泻以及白细胞下降导致的发热等。大部分患者为Ⅰ、Ⅱ度反应,患者耐受良好。结论多西他赛联合卡铂是一种对晚期非小细胞肺癌有效的治疗方法,毒性反应轻,临床使用安全。     

A phase II trial of a differentiating agent (tRA) with cisplatin-VP 16 chemotherapy in advanced non-small cell lung cancer

Summary The prognosis for advanced non-small cell lung cancer remains poor. Response to chemotherapy is infrequent and overall survival is low. Trans-retinoic acid (tRA), a differentiating agent whose mechanism of action is thought to be different from conventional chemotherapy has activity in preclinical models and low but definite activity in the clinical setting. Its use has been hampered by decrease in bioavailability during continuous administration. We used an interrupted dosing schedule with a drug holiday for tRA that has since been confirmed to restore blood levels in combination with chemotherapy (Cisplatin-VP 16) in 20 patients with stage IIIB and IV non-small cell lung cancer. Ten patients had partial responses among 19 evaluable pts (53%; 95% confidence interval 30–75%) and 4 had minor responses. Neutropenia was the most common acute toxicity-grade 3/4 neutropenia occurring in 90% of patients at some point in the treatment course. Median survival was 25.5 weeks.This regimen of trans-retinoic acid given with drug holiday and chemotherapy has significant activity in advanced non-small cell lung cancer, is fairly well tolerated and is worthy of confirmation in a larger, multi-institutional setting.     

Phase II study of weekly docetaxel and cisplatin in patients with non-small cell lung cancer

We conducted a phase II study to examine the efficacy and safety of weekly docetaxel and cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC). Forty chemotherapy-naive patients (10 with stage IIIB and 30 with stage IV NSCLC) with an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ functions were enrolled. Chemotherapy consisted of cisplatin (80 mg/m2) on day 1, and docetaxel (35 mg/m2) on days 1, 8 and 15, delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. There were 18 partial responses, with an overall response rate of 45% (95% confidence interval 29.6-60.4%) in 40 treated patients. The median survival period was 19.9 months, median progression-free survival was 5.5 months and 1-year survival rate was 69.4%. Hematologic toxicities were mild and included grade 3 or 4 neutropenia in 37.5%. There were no severe infections or septic deaths. Non-hematologic toxicities were generally mild. Grade 3 or 4 transaminase elevations were observed in two patients. Grade 3 events included two cases each of vomiting, and one case each of hypokalemia, diarrhea and creatinine elevations. Weekly docetaxel and cisplatin is an effective and safe combination in the treatment of patients with advanced NSCLC.     

Pulmonary toxicity in patients treated with gemcitabine plus vinorelbine or docetaxel for advanced non-small cell lung cancer: outcome data on a randomized phase II study

Studies with the gemcitabine/vinorelbine (GV) or the gemcitabine/docetaxel (GD) combinations have shown similar efficacy and less toxicity compared to platinum-based chemotherapies, in patients with advanced non-small-cell lung cancer (NSCLC). The present trial was designed to test the efficacy and safety of both, GV and GD, combinations. Chemotherapy-na?ve patients (n=39)or=60% and adequate hematological, renal and hepatic function were randomly assigned to receive G 1,000 mg/m2+either V 25 mg/m2 or D 35 mg/m2 (all of which were administered i.v.) on days 1 and 8 every 21 days. Baseline characteristics were comparable in GV (n=20) and GD (n=19) groups. Results indicated objective response of 7 (35%) vs 6 (31%) patients and median time-to-treatment failure of 120 versus 90 days in the GV and GD arms, respectively. The most common non-hematological toxicities were (GV vs GD): grade 2-4 pulmonary toxicity in 1 (5%) vs 7 (37%); grade 2-3 diarrhea 0 versus 4 (21%) and edema 1 (5%) vs 3 (16%); grade 3-4 hematological toxicities occurred in 3 (15%) vs 1 (5%) patients. Our results indicate that the combination of gemcitabine/docetaxel does not have a favorable safety profile with this schedule of administration, particularly in terms of pulmonary toxicity.     

The current status of docetaxel for advanced non-small cell lung cancer

Docetaxel is an active single agent in both first- and second-line therapy of patients with advanced non-small cell lung cancer (NSCLC). Randomized trials versus best supportive care have documented an improvement in overall survival for docetaxel therapy in both settings. Docetaxel also produced a significant 1-year survival rate improvement when compared with vinorelbine or ifosfamide as second-line therapy. Docetaxel has been extensively investigated in phase I/II studies in combination with cisplatin, carboplatin, irinotecan and gemcitabine. Substantial activity has been demonstrated. In a randomized phase II trial comparing docetaxel plus cisplatin with docetaxel plus gemcitabine, the efficacy of the two regimens was almost identical (response rates 32 and 34%; 1-year survival rates 42 and 38%). However, the combination of docetaxel with gemcitabine was associated with significantly less grade III/IV neutropenia, diarrhea and nausea/vomiting. Three drug regimens combining docetaxel with, for example, gemcitabine and carboplatin or with ifosfamide and cisplatin, are producing very high response rates in phase II trials. Whether three-drug combinations including docetaxel will result in an improved outcome for patients with advanced NSCLC remains to be determined.     

A cost-effectiveness analysis of docetaxel in the second-line treatment of non-small cell lung cancer

BACKGROUND: Whilst lung cancer is the most common form of cancer in England and Wales (annual incidence rate of 50 per 100,000) it does not always receive the policy attention accorded to other types of cancer, such as breast and colorectal. Nevertheless, the burden of lung cancer is significant and the UK NHS Plan for cancer has set out the government's commitment to improving all cancer services. The question faced by the NHS is which interventions are most cost effective in implementing this plan. OBJECTIVE: To develop a model to assess the economics of second-line treatment of non-small cell lung cancer (NSCLC) from the perspective of the UK NHS, based on the resources and outcomes from the pivotal clinical study comparing docetaxel 75 mg/m(2) with best supportive care (BSC). METHODS: The area under the survival curve for each treatment was analysed and the difference in mean survival between the docetaxel group and the BSC group was calculated as 3.82 months. Measurable incremental costs for the docetaxel group were largely driven by drug acquisition and administration. These cost drivers, as well as toxicity treatment costs and cost offsets, were varied in the sensitivity analysis. Although the overall timeframe for the model was 2 years, discounting was not applied as the resources and benefits of docetaxel use in this setting are realised relatively immediately. RESULTS: The base case cost-effectiveness analysis (mean values) reported a cost per life-year gained of 13,863 pounds sterling for docetaxel 75 mg/m(2) (year 2000/2001 values). Sensitivity analysis showed that the number of treatment cycles per patient, which affected total treatment cost, had most influence on the cost per life-year gained in the base case scenario. Using the 95% confidence intervals around the mean number of treatment cycles, the base case cost per life-year gained varied from 10,985 pounds sterling to 16,738 pounds sterling. Using the 95% confidence intervals around the mean difference in survival, to represent best and worst case scenarios, the cost per life-year saved ranged from 10,020 pounds sterling to 32,781 pounds sterling . CONCLUSION: This model suggests, with its underlying assumptions and data, docetaxel 75 mg/m(2) in 3-weekly cycles is a cost-effective second-line treatment, from the perspective of the NHS, for pretreated NSCLC in terms of survival gains made for a reasonable increase in costs.     

多帕菲联合顺铂化疗在局部晚期非小细胞肺癌中的应用评价

目的探讨多帕菲(docetaxel)联合顺铂(DDP)方案治疗局部晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法选取初治晚期非小细胞肺癌43例,采用多帕菲加顺铂方案联合化疗,多帕菲按总量150 mg·m-2静滴分第1,2天;顺铂按75mg·m-2分3 d静滴,即第3,4,5天,21 d为一周期;按WHO疗效及不良反应评价标准,完成2～3个周期治疗的患者进行临床疗效及不良反应评估.结果可评价患者43例,其中完全缓解(CR)5例占11.6%(5/43),部分缓解(PR)19例占44.2%(19/43),总有效(CR PR)为占55.8%(24/43),中位生存期为9.2个月,1年生存率40%(16/40).全组不良反应主要为血液学毒性,其中白细胞降低发生率为51.16%(22/43),血小板下降发生率为9.3%(4/43),血红蛋白下降发生率为4.7%(2/43),非血液学毒性有胃肠道反应和脱发等.结论多帕菲联合顺铂治疗晚期非小细胞肺癌较好疗效,不良反应可耐受,安全性高,可在临床推广应用.     

多西他赛联合顺铂治疗晚期非小细胞肺癌26例

目的:探讨多西他赛联合顺铂4 wk治疗晚期非小细胞肺癌方案的疗效和安全性。方法:经病理组织学或细胞学确诊的ⅢB期或Ⅳ期非小细胞肺癌病人26例,年龄在35-78 a,ECOG PS评分为0-2分;d 1,8 多西他赛37．5 mg·m-2,d 1-3顺铂75-100 mg·m-2,分3 d,均予静脉滴注。每4 wk重复,2个周期后评价疗效与不良反应,并随访生存期。结果:24例可评价疗效病人中,部分缓解(PR)8例,完全缓解(CR)1例,总有效率为38％。ECOG PS评分0-1分病人有效率明显高于ECOG PS评分2分病人。中位生存期为11 mo,1年生存率为50％。Ⅲ-Ⅳ度白细胞减少的发生率为20％。结论:多西他赛联合顺铂4 wk方案治疗晚期非小细胞肺癌安全且有效。     

培美曲塞或多西他赛治疗老年晚期非小细胞肺癌的疗效观察

目的:探讨单药二线培美曲塞或多西他赛治疗老年晚期非小细胞肺癌的疗效和不良反应.方法:老年复发晚期非小细胞肺癌患者58例,28例单药培美曲塞化疗:培美曲塞500 mg/m2,第一天静脉滴注,每3周为1周期;30例单药多西他赛化疗:多西他赛40mg/m2,第一、八天静脉滴注,每3周为1周期.结果:培美曲塞组和多西他赛组有效率分别为25.0％、23.3％,中位生存期分为9.8个月、8.1个月,1年生存率分别为19.2％、20.0％.两组差异无统计学意义(P＞0.05),两组不良反应均可耐受,培美曲塞组未发生Ⅲ度和Ⅳ度血液学不良反应差异有统计学意义(P＜0.05).结论:老年晚期非小细胞肺癌患者可从二线单药培美曲塞或多西他赛化疗中获益,培美曲塞不良反应轻微.     

多西他赛联合顺铂治疗晚期非小细胞肺癌的临床分析

目的探讨多西他赛联合顺铂治疗晚期非小细胞肺癌的疗效和毒副反应。方法应用多西他赛75mg/m2联合顺铂75mg/m2方案治疗38例晚期非小细胞肺癌患者。结果总有效率达36.8%,其中初治组有效率为41.2%,复治组有效率为33.3%。主要毒副反应为骨髓抑制、恶心呕吐、腹泻及周围神经炎等。结论多西他赛联合顺铂治疗晚期非小细胞肺癌有较好疗效,毒副反应可耐受。     

Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine

Gemcitabine is widely used for the treatment of advanced biliary tract cancer (BTC) as first-line chemotherapy. However, there is no standard chemotherapy for patient with advanced BTC refractory to gemcitabine. We conducted a multicenter phase II study of S-1 monotherapy as second-line chemotherapy for patients with advanced BTC that were refractory to gemcitabine. S-1 was administered orally at a dose of 80 mg/m(2) for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty-two patients were enrolled between March 2007 and January 2010, with 14 patients (64%) representing cases of recurrence after surgery. The overall response rate was 22.7%, and the overall disease control rate was 50.0%. The median overall survival time was 13.5 months (95% CI, 7.1-23.1 months) and the median time-to-progression was 5.4 months (95% CI, 2.6-17.2 months). Grade 3/4 toxicities included neutropenia (5%) and anemia (5%). The most common non-hematological toxicities were nausea (27%), anorexia (55%), and pigmentation (32%). In conclusion, S-1 monotherapy is feasible and moderately efficacious second-line chemotherapy for advanced BTC.     

培美曲塞二线治疗老年非鳞非小细胞肺癌的回顾分析

目的:观察培美曲塞二线治疗老年非鳞非小细胞肺癌(NSCLC)的疗效和不良反应。方法:收集我院从2012年7月至2013年4月住院治疗的70岁以上的晚期非鳞NSCLC患者58例并进行疗效和不良反应回顾性分析。患者均为一线化疗失败或不能耐受者。采用培美曲塞500mg·m-2静脉滴注,每3周1次,共6个周期。结果:本组完全缓解(CR)0例,部分缓解(PR)6例,疾病稳定(SD)20例,SD持续时间大于6个月的12例,疾病进展(PD)32例。总有效率(RR=CR+PR)为10.3%,临床获益率(CR+PR+SD>6个月)为31.0%,中位无疾病进展时间(PFS)为3.4个月(2.0⁸.9个月)。完成6周期治疗的患者10例。主要毒性反应为骨髓抑制、胃肠反应和疲劳。结论:70岁以上的、一线化疗失败的非鳞NSCLC患者能从二线培美曲塞治疗中获益,耐受性良好。     

晚期非小细胞肺癌患者化疗用药合理性评估

目的：评价晚期非小细胞肺癌患者药物治疗方案的合理性,以期为临床合理用药提供参考。方法：收集2014年4月—2015年3月某院收治的120例非小细胞肺癌患者资料,统计患者化疗方案、辅助用药、治疗过程监测以及化疗相关不良反应情况。结果：120例患者共使用11种含铂两药化疗方案,以吉西他滨联合奈达铂的治疗方案用药频度最高,构成比为28.08%。有43例次化疗中,一种化疗药超剂量使用。6种辅助用药DUI>1。中药注射剂与止吐药用药频度最高,分别为3 754.8 DDD和3 985.0 DDD。盐酸托烷司琼注射液、注射用埃索美拉唑和和痰热清注射液的药物利用指数居前三位,分别为1.8、1.4和1.4。在药物选择、给药剂量、配置浓度以及异常检验指标的复查方面,存在一些有待改进之处。结论：某院晚期非小细胞肺癌的药物治疗方案基本贯彻指南要求,但在给药剂量、治疗过程监测、中药注射剂的使用方面仍需进一步规范。     

尼妥珠单抗联合化疗治疗30例晚期非小细胞肺癌的临床观察

目的:回顾性分析尼妥珠单抗联合化疗治疗晚期非小细胞肺癌的临床疗效和安全性。方法:纳入中国医学科学院肿瘤医院2011年1月至2014年12月30例经病理组织学或细胞学确诊的晚期非小细胞肺癌患者,其中腺癌19例、鳞状细胞癌8例、未知型3例。所有患者均接受尼妥珠单抗联合化疗的治疗,其中19例采用含铂类方案,11例采用非含铂类方案。尼妥珠单抗给药剂量为200 mg,静脉给药,每周1次。尼妥珠单抗联合化疗作为一线方案患者5例,二线方案9例,三线及以上方案16例。每治疗2个周期后按照实体瘤疗效评价标准(RECIST)1.1进行疗效评价;采用NCI-CTCAE3.0标准评价不良反应。结果:30例患者均完成了至少一次疗效评价,其中无完全缓解(CR),部分缓解(PR)5例,疾病稳定(SD)12例,病情进展(PD)13例;客观缓解率(ORR)为16.7%(5/30),疾病控制率(DCR)为56.7%(17/30),中位无进展生存时间(PFS)为89 d(74~104 d),中位总生存时间(OS)为307d(197~417 d)。进一步分析显示,腺癌患者中位OS显著长于鳞癌患者(327 d vs 185 d,P=0.008)。药物安全性评价结果显示尼妥珠单抗联合化疗的安全性良好。结论:尼妥珠单抗联合化疗治疗非小细胞肺癌疗效确切,不良反应较轻,值得临床进一步研究。