多西他赛单药二线治疗33例晚期非小细胞肺癌疗效观察

目的：评价单药多西他赛作为二线治疗对晚期非小细胞肺癌（NSCLC）的疗效和不良反应。方法：33例经病理和（或）细胞学检查诊断为晚期非小细胞肺癌,曾用含有铂类方案化疗,治疗后复发或进展接受多西他赛75rag／甜静滴1小时,第一天,每3周重复。结果：可评价疗效33例中,无完全缓解（CR）,部分缓解（PR）12．1％（4／33）,稳定（SD）51．5％（17／33）,进展（PD）36．4％（12／33）,有效率12．1％（4／33）,中位生存期8．5个月,1年生存率33．3％（11／33）。不良反应主要是血液学毒性,可以耐受。结论：多西他赛单药用于二线化疗治疗晚期非小细胞肺癌疗效肯定,耐受性较好。     

吉西他滨联合顺铂方案二线治疗晚期非小细胞肺癌的临床观察

目的：观察吉西他滨联合顺铂二线治疗晚期非小细胞肺癌的疗效及不良反应。方法：对38例晚期非小细胞肺癌患者采用二线化疗,入组患者均经病理组织学证实,有可测量病灶,方案为吉西他滨1000mg／m^2第1、8天,顺铂80mg／m^2,分3天应用,21天为1个周期。化疗2个周期后评价疗效及不良反应。结果：所有患者均可评价,共进行108周期的化疗。完全缓解（CR）0例,部分缓解（PR）11例,稳定（SD）12例,进展（PD）15例,总有效率28．9％。中位缓解时间4．5月,中位生存时间7．8月。主要不良反应为血液学毒性,其中Ⅲ／Ⅵ度的中性粒细胞下降、血小板下降和血红蛋白下降分别为18．5％（20／108）、11．1％（12／108）和8．3％（9／108）,其次为消化道不良反应,Ⅲ／Ⅵ度的食欲下降和恶心呕吐分别为13．9％（15／108）和12．0％（13／108）。结论：吉西他滨联合顺铂对复治晚期非小细胞肺癌有较好疗效,不良反应可以耐受。     

易瑞沙治疗晚期非小细胞肺癌的临床获益分析

目的：探讨选择性表皮生长因子受体抑制剂易瑞沙（IRESSA）治疗晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）的临床疗效及不良反应。方法：对既往化疗失败或不能耐受拒绝化疗的晚期NSCLC患者23例，单药IRESSA 250mg，口服，每日1次，服用至病情进展或出现不可耐受的不良反应。患者分别在治疗后30、90d对其疗效及不良反应进行观察统计。结果：23例中22例可评价疗效，其中CR1例，PR6例，SD10例，PD5例，有效率31．8％（7／22），患者疾病控制率（CR＋PR＋SD）77．3％（17／22）。治疗后30d肿瘤相关症状缓解率为73．9％（17／23）。Karnofsky评分，治疗前总分数900，人均39．1；治疗后总分数1380，人均60；治疗前后比较差异有统计学意义，t=3．18，P=0．004。常见不良反应为腹泻和皮肤改变，Ⅳ级占4．3％（1／23）。结论：IRESSA单药对化疗失败或不能耐受的晚期NSCLC疗效确切，改善症状明显，用药方便，不良反应轻。     

吉西他滨联合顺铂治疗晚期非小细胞肺癌的临床研究

目的 观察吉西他滨（gemcitabine，GEM）联合顺铂方案治疗晚期非小细胞肺癌的疗效及不良反应。方法 对经病理组织学或细胞学诊断证实的56例晚期非小细胞肺癌患者采用GP方案行静脉化疗：GEM1000mg／m^2，静脉滴注，d1，d8；DDP30mg／m^2，静脉滴注，d1～d3；21天重复，至少治疗2个周期。结果 可评价疗效56例，完全缓解（CR）5．3％（3／56），部分缓解（PR）42．9％（24／56），稳定（SD）33．9％（19／56），进展（PD）17．9％（10／56），总有效率（RR）48．2％（27／56）；肿瘤控制率（CR＋PR＋SD）为82．1％（46／56）；中位缓解期7．4个月，中位生存期11．3个月；不良反应以白细胞及血小板减少，消化道反应，乏力为常见，患者均可耐受，无化疗相关死亡。结论 吉西他滨联合顺铂对晚期非小细胞肺癌有较好疗效，不良反应可为患者所耐受，值得临床应用。     

IRESSA治疗晚期难治性非小细胞肺癌的临床研究

背景与目的 化疗是晚期非小细胞肺癌的主要治疗手段，但是非小细胞肺癌常常对化疗耐药，先天性耐药或获得性耐药是导致非小细胞肺癌化疗失败的主要原因之一，因此寻找理想的新的抗癌药物是临床肿瘤学家的共同目标。本文旨在观察IRESSA对晚期耐药非小细胞肺癌的疗效和不良反应。方法 应用口服IRESSA 250mg／d治疗晚期耐药非小细胞肺癌100天后观察疗效。结果 33例Ⅳ期耐药非小细胞肺癌患者中32例完成口服IRESSA 100天，可评价疗效，其中完全缓解1例（3．1％），部分缓解11例（34．4％），稳定9例（28．1％），进展11例（34．4％）。有效率为37．5％，疾病控制率为65．6％。全组中位肿瘤进展时间为5．7个月，总生存期为3．3～25．9个月（中位生存时间9．6个月），9例生存时间超过1年，1年生存率为28．1％，2例生存时间超过2年，2年生存率为6．3％，最长1例存活25．9个月。IRESSA的疗效与病理类型有一定关系，肺泡细胞癌效果最佳，其次为腺癌、鳞癌。主要不良反应包括：皮疹28例（84．8％），皮肤瘙痒31例（93．9％），四肢关节疼痛9例（27．3％），腹泻25例（75．8％），食欲减退29例（87．9％），恶心14例（42．4％），呕吐4例（12．1％），头晕5例（15．2％），头痛4例（12．1％），胸闷13例（39．4％），腹痛3例（9．1％），间质性肺炎1例（3．0％），大部分不良反应可以耐受，仅1例原有慢性肺部纤维化疾病者出现严重间质性肺炎，最终因为呼吸功能衰竭导致死亡。无心电图及肝肾功能改变。结论 IRESSA对晚期耐药非小细胞肺癌具有较好的疗效，不良反应轻微，可以耐受，可以考虑做为晚期非小细胞肺癌的三线治疗方案，并且可以考虑做为一些体质较差、不能耐受手术、放疗或化疗的非小细胞肺癌患者的一线治疗。     

去甲长春花碱加顺铂治疗晚期肺部恶性肿瘤的临床研究

目的：观察去甲长春花碱联合顺铂治疗晚期原发性非小细胞肺癌和继发性肺癌的临床疗效及不良反应。方法：38例均有组织学或细胞学病理诊断及影像学诊断，有可评价的客观指标。采用去甲长春花碱25mg／m^2，静脉快速滴人，第1、8天，然后用生理盐水100ml加地塞米松10mg静脉滴人冲洗血管。顺铂30mg／m^2静滴，第1～3天，21天为1周期，2个周期评价疗效。结果：38例可评价疗效和不良反应。CR 0例，PR 9例，NC16例，PD13例，总有效率(CR PR)为23．68％。中位生存期5个月。不良反应主要为白细胞减少Ⅱ-Ⅲ度占44．74％(17／38)，Ⅳ度占13．16％(5／38)；局部静脉炎占36．84％(14／38)。结论：去甲长春花碱联合顺铂治疗晚期原发性非小细胞肺癌和继发性肺癌有肯定的疗效，可相应提高晚期患者的生存率，不良反应可以耐受。     

吉西他滨联合顺铂方案二线治疗晚期非小细胞肺癌的临床观察

目的：观察吉西他滨联合顺铂二线治疗晚期非小细胞肺癌的疗效及毒性反应。方法：从2000年3月～2004年10月对38例晚期非小细胞肺癌患者采用二线化疗,入组患者均经病理组织学证实,有可测量病灶,具体为吉西他滨1000mg／m。第1、8天,顺铂80mg/m^2,分3天应用,21天为1个周期。化疗2个周期后评价疗效及毒副反应。结果：所有患者均可评价,总共进行108周期的化疗。完全缓解（CR）0例,部分缓解（PR）11例,稳定（SD）12例,进展（PD）15例,总有效率28．9％。中位缓解时间4．5月,中位生存时间7．8月。主要不良反应为血液学毒性,其中Ⅲ／Ⅳ度的中性粒细胞下降、血小板下降和血红蛋白下降分别为18．5％（20／108）、11．1％（12／108）和8．3％（9／108）。其次为消化道毒性,Ⅲ／Ⅳ度的食欲下降和恶心呕吐分别为13．9％（15／108）和12．0％（13／108）。结论：吉西他滨联合顺铂对复治晚期非小细胞肺癌有较好疗效,毒副反应可以耐受。     

NP方案二线化疗对25例晚期非小细胞肺癌的疗效

目的 探索二线化疗方案对晚期非小细胞肺癌(NSCLC)的疗效和不良反应。方法 采用NP方案即进口长春瑞宾(NVB)25mg／m^2，iv，第l，8天；顺铂(DDP)80mg／m^2，iv，第l天；作为二线方案治疗经病理和(或)细胞学诊断的25例晚期NSCLC。22例曾用含铂类方案化疗，经用1个化疗方案治疗后复发或进展。结果 可评价疗效的25例中，无CR(完全缓解)，PR(部分缓解)3例，SD(稳定)14例，PD(进展)8例，有效率12％；中位生存期9个月；1年生存率36％。3例获PR者病理诊断均为腺癌，治疗后生存期分别为7个月、16个月和16个月。化疗的不良反应主要是血液学毒性，但患者可以耐受。结论 NVB联合DDP用于二线化疗方案治疗晚期NSCLC临床有效，患者耐受性尚可，应开展进一步的随机研究。     

单药泰索帝每周方案治疗晚期老年人非小细胞肺癌64例疗效观察

目的:研究和评价单药泰索帝每周方案治疗晚期老年人非小细胞肺癌的临床疗效和不良反应。方法:对1999年11月至2005年2月我院收治的64例年龄在65至84岁的老年晚期非小细胞肺癌患者,应用单药泰素帝每周用药剂量为25mg/m2化疗,连续6周,休息2周,评价疗效和毒性反应。其中25例病人为一线化疗,另39例为二线用药。结果:64例患者共经历448周泰素帝化疗,近期有效24例(37.5%),保持稳定或微效26例(40.6%),中位病情无进展期28周,中位生存期44周。主要毒性反应为乏力,体质下降,发生率20%。骨髓抑制多为1~2度,4度骨髓抑制患者仅1例。结论:单药泰索帝每周方案治疗晚期老年人非小细胞肺癌患者有一定疗效,毒性反应轻微,可使患者病情进展延缓,中位生存期延长。     

吉非替尼挽救性治疗晚期非小细胞肺癌的初步观察

为了观察吉非替尼（gefitinih）挽救性治疗化疗失败的晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）的疗效和不良反应，给45例化疗失败的晚期NSCLC患者口服吉非替尼250mg／d，直至病情进展或不能耐受毒性（至少30d）。结果 全组总有效率为51．1％（23／45），其中CR3例，PR20例，SD5例，疾病控制率为62．2％（28／45）。中位生存时间为4个月，其中有效者为7个月，无效者则为2个月．1年生存率为21．3％。不良反应主要为Ⅰ～Ⅱ度皮疹（64．4％）、腹泻（31．1％）和恶心呕吐（24．4％）。初步研究结果提示，吉非替尼治疗化疗失败的晚期NSCLC的疗效好，不良反应轻，有望成为晚期NSCLC一线或二线治疗标准。     

多西他赛二线治疗晚期非小细胞肺癌疗效观察

目的 评价单药多西他赛作为二线化疗对晚期非小细胞肺癌(NSCLC)的疗效和毒副反应.方法 15例经病理和(或)细胞学确诊的晚期非小细胞肺癌,曾用含铂类方案化疗,治疗后复发或进展,采用多西他赛35 mg/m2静滴1 h,d1,8,15,每4周重复.结果 可评价疗效的15例中,完全缓解(CR)0%(0/15),部分缓解(PR)13.3%(2/15),稳定(SD)46.7%(7/15),进展(PD)40%(6/15),有效率13.3%(2/15),中位生存期8个月,1年生存率40%(6/15),骨髓抑制为其剂量限制性毒性,患者可耐受.结论 多西他赛单药二线治疗晚期非小细胞肺癌疗效肯定,耐受性较好.     

A phase II trial of weekly paclitaxel and gemcitabine in non-small cell lung cancer patients previously treated with platinum and vinorelbine

This study evaluated the activity and toxicity of a weekly paclitaxel plus gemcitabine combination as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel 80 mg/m2 on days 1, 8 and 15 and gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks were administered to 34 consecutive, advanced NSCLC patients uniformly pretreated with cisplatin or carboplatin and vinorelbine. The median time interval from first- to second-line treatment was 8 weeks (range 1-72). A total of 124 cycles with a median of 3 cycles per patient were administered (range 1-6). Four patients (12%) achieved a partial response (95% confidence interval: 1-23%), 17 had stable disease (50%) and 12 progressed (37%). Three responses were observed in 14 patients showing disease response or stabilization to previous platinum therapy. The median survival was 28 weeks (range 3-91), the median progression-free survival was 12 weeks (range 3-50) and the 1-year survival rate was 23%. The toxicity profile was favorable. In conclusion, a weekly schedule of paclitaxel plus gemcitabine as a second-line regimen has moderate activity and good tolerability in NSCLC patients not refractory to previous platinum-vinorelbine treatment.     

A Phase II trial of topotecan and gemcitabine in patients with previously treated,advanced nonsmall cell lung carcinoma

BACKGROUND: Multiple trials have been performed to evaluate second-line clinical chemotherapy in patients with advanced nonsmall cell lung carcinoma (NSCLC). However, no single agent or combination has demonstrated superior activity. METHODS: Patients with advanced NSCLC who had already received one chemotherapeutic regimen were treated with topotecan (0.75 mg/m(2) over 30 minutes, Days 1-5) and gemcitabine (400 mg/m(2) over 30 minutes, Days 1 and 5) every 21 days. RESULTS: Of 35 patients who were treated, 4 (11%) achieved a partial responses and 8 (23%) hadstable disease for at least four courses of treatment. The response rate for patients with refractory disease (progressing during frontline chemotherapy) was 18% (3 of 17) with 18% having stable disease for at least four courses of treatment. The median survival of the entire group was 7 months (range, 1.5-44 months) and 20% (7 of 35) of patients were alive 1 year from the initiation of topotecan and gemcitabine treatment. Patients with refractory disease had a median survival of 4(1/2) months, with 6-month and 1-year survival rates of 47% and 18%, respectively. During Course 1, five patients (14%) developed Grade IV neutropenia and three patients (9%) developed Grade IV thrombocytopenia. Nonhematologic toxicity was relatively mild, with one patient developing Grade III side effects (fatigue) and eight patients (23%) developing Grade II nonhematologic side effects. CONCLUSIONS: The combination of topotecan and gemcitabine demonstrated antitumor activity with a modest side effect profile in patients with advanced, previously treated NSCLC.     

Docetaxel and cisplatin as second-line chemotherapy for advanced non-small cell lung cancer

AIMS AND BACKGROUND: Docetaxel and cisplatin are both active against non-small cell lung cancer (NSCLC). This pilot study evaluated the efficacy and toxicity of docetaxel and cisplatin as second-line chemotherapy for patients with advanced NSCLC. PATIENTS AND METHODS: Eleven patients with advanced NSCLC who had no response to platinum-based treatment or had recurrence after a partial response were enrolled (2 stage III B, 9 stage IV; 8 men, 3 women). Median age was 58 years (range, 40 to 74 years). Seven patients had an Eastern Cooperative Oncology Group performance status of 0, and four had a performance status of 1. Four weeks or more after the end of previous therapy, all 11 patients received docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 every four weeks. RESULTS: Two patients (18.2%) achieved a partial response,five (45.4%) patients had stable disease, and four (36.4%) patients showed progressive disease after initiation of second-line therapy. Median survival was 277 days. Median time to disease progression was 101 days, and the one-year survival rate was 36.4%. Hematological toxicities were moderate. Grade 3 and 4 leukocytopenia and neutropenia were observed in five (45.4%) patients. Grade 3 anemia occurred in one (9 .1%) patient. No severe non-hematological toxicities were observed except grade 3 nausea in two (18.2%) patients. CONCLUSIONS: The regimen of docetaxel and cisplatin has reasonable efficacy with moderate toxicity as second-line chemotherapy for patients with previously treated, advanced NSCLC.     

吉非替尼治疗化疗失败的晚期非小细胞肺癌临床观察

目的:评价吉非替尼治疗化疗失败的晚期非小细胞肺癌(NSCLC)的疗效及不良反应。方法:对68例化疗失败的经病理或细胞学证实的晚期NSCLC患者给予吉非替尼250mg,qd,口服,至病情进展或出现不可耐受的不良反应。结果:68例患者中,CR 1例,PR 20例,SD 23例,PD 24例。有效率30.88%(21/68),疾病控制率为64.71%(44/68);全组中位疾病进展时间(TTP)为5.2个月,中位生存时间为9.3个月,1年生存率为52.94%(36/68)。与药物相关的不良反应主要为Ⅰ、Ⅱ度皮疹和腹泻,皮疹发生率为26.47%(18/68),腹泻发生率为19.12%(13/68),多在用药后1周内出现,症状轻不需特殊处理。1例出现Ⅰ度转氨酶升高。结论:吉非替尼治疗化疗失败的晚期非小细胞肺癌安全有效,不良反应轻微,患者耐受性和依从性良好。     

Single agent gemcitabine in the second-line treatment of advanced non-small cell lung cancer after treatment with taxane + platinum regimens

In this study, we investigated the activity of single agent gemcitabine in the second-line setting of non-small cell lung cancer (NSCLC). File records of 21 patients treated with single agent gemcitabine in advanced NSCLC who received one prior chemotherapy including a taxane and platinum combination were retrospectively evaluated. Treatment consisted of IV gemcitabine 1,250 mg/m2 on days 1 and 8, followed by a 1-week rest repeated every 3 weeks. A partial response was achieved in four (19%) patients. The median response duration was 16 (range, 12-32) weeks. Six (29%) patients had a SD more than 3 months. The median time to progression was 16 (range, 8-32) weeks. No complete response was observed. Median overall survival was 36 weeks for second-line gemcitabine in all patients (95%: CI 5-13 months). Hematological toxicity (all grades) was reported by 9 (42.9%) patients. One (4.75%) patient experienced grade 3/4 neutropenia. Grade 3/4 nausea and vomiting and mucositis were reported in one (4.75%) patient. In conclusion, this study shows that single agent gemcitabine is active and well tolerated as a second-line therapy for advanced NSCLC.     

Phase II trial of karenitecin in patients with relapsed or refractory non-small cell lung cancer (CALGB 30004)

PURPOSE: This Phase II trial was designed to determine the response rate, survival, failure-free survival, and toxicity of second-line therapy with karenitecin in patients with relapsed or refractory non-small cell lung cancer (NSCLC). METHODS: Eligibility criteria included: only one prior chemotherapy program, measurable disease, performance status 0-1, adequate hematologic, renal, and hepatic function. Cases were stratified as relapsed or refractory. RESULTS: Fifty-five patients were accrued and 52 were eligible of whom 28 had relapsed and 24 had refractory disease. Overall patient characteristics were: median age 63 years (range, 45-79 years), 52% males, 63% performance status 1, 50% adenocarcinoma, 21% squamous, 15% large cell, and 12% undifferentiated NSCLC. In both strata, one patient each (4%) had a partial response and 12 patients each (43% for relapsed, 50% for refractory) had stable disease. Median survival was 10.4 months (95% CI, 8.5-17.0) for relapsed NSCLC and 6.0 months (95% CI, 3.7-9.7) for refractory NSCLC. One-year survival was 36% (95% CI, 14-58%) and 21% (95% CI, 5-37%) for relapsed and refractory NSCLC, respectively. Frequent toxicities were neutropenia (grade 3/4 in 15/15%) and thrombocytopenia (grade 3/4 in 17/8%). No patient had lethal toxicity. CONCLUSION: Second-line treatment with karenitecin was tolerable with reversible bone marrow suppression as the major toxicity. The partial response rates, median survival times, and 1-year survival rates in the relapsed and refractory subgroups are comparable to overall second-line outcomes for other agents considered active in this clinical setting.     

Gemcitabine and vinorelbine as second-line therapy in non-small-cell lung cancer after prior treatment with taxane+platinum-based regimens

Treatment options in patients with recurrent non-small-cell lung cancer (NSCLC) remain limited as a result of the poor activity of older agents after platinum-based therapy. The present phase II study aimed to evaluate the combination of gemcitabine and vinorelbine in patients with relapsed NSCLC after pretreatment with taxane+platinum-based regimens, since gemcitabine has demonstrated activity in that setting and the combination has been well tolerated in previous phase I/II studies. Patients with advanced NSCLC (stages III/IV), World Health Organization (WHO), Performance Status (PS) < or = 2, prior platinum+taxane-based chemotherapy and unimpaired haematopoietic and organ function were eligible. Chemotherapy was administered as follows: vinorelbine 25 mg/m(2) followed by gemcitabine 1000 mg/m(2), both administered on days 1 and 8, recycled every 3 weeks. 40 patients were entered and 39 were evaluable for response and all 40 for toxicity: median age was 61 years (range 50-72 years), median PS=1 (range 0-2), gender ratio=37 males/3 females, stages at initial diagnoses were IIIA=2, IIIB=14, IV=24. Metastatic sites included: lymph nodes: 23, bone: 4, liver: 5, brain: 4, lung nodules: 9, adrenals: 8, pleural effusion: 4. 22 patients had prior paclitaxel/ifosfamide/cisplatin treatment. Objective responses were; partial response (PR): 9/40 (22.5%), stable disease (SD): 13/40 (32.5%) and progressive disease (PD) 18/40 (45%). The median time-to-progression (TTP) was 4.5 months (range 1-17 months) and median survival 7 months (range 2-17+ months). 1-year survival was 17%. Grade 3 neutropenia was seen in 33% of patients. There was no grade 4 neutropenia and no episodes of febrile neutropenia. No grade 3/4 thrombocytopenia or grade 3/4 other non-haematological toxicities were observed. The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC failing prior taxane/platinum therapy. This regimen represents a tolerable and effective combination to apply in the palliative treatment of relapsed NSCLC.     

Sequential administration of docetaxel followed by maintenance gefitinib, as salvage treatment in patients with advanced NSCLC: a multicenter phase II trial

PURPOSE: To evaluate the activity and toxicity of the sequential administration of docetaxel followed by gefitinib in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Forty-one patients pre-treated with at least one prior chemotherapy regimen (platinum- or taxane-based) for advanced/metastatic NSCLC received three cycles of docetaxel 30 mg/m2, administered as a 1-h IV infusion, on days 1, 8 and 15 of each 4-week cycle followed by gefitinib 250 mg daily po. Gefitinib treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of patients consent. RESULTS: Two (4.9%) patients achieved a partial response and 10 (24.4%) stable disease, for a disease control rate of 29.3% (95% CI: 15.3%-43.2%) while on weekly docetaxel treatment. Additionally, progressive disease (PD) was observed in 29 (70.7%). No objective responses were observed during the gefitinib maintenance therapy; however, 17 (41.5%) patients presented stable disease maintained for more than 2 months. Median time to progression was 3.0 months (range: 1-38.3 months; 95% CI: 2.4-3.6); median overall survival 6.9 months (range: 1.2-40.2 months; 95% CI: 5.34-8.52) while the 1-year survival was 28.8%. Therapy was generally well tolerated with diarrhea and rash being the most frequent toxicities. CONCLUSIONS: The sequential administration of docetaxel and gefitinib was well tolerated and moderately active against advanced pre-treated NSCLC.