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.     

Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer

Purpose: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m²) followed by mitomycin C (8 mg/m²) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. Results: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3–4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6–21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. Conclusions: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.     

多西他赛二线治疗23例晚期非小细胞肺癌

目的：评价单药多西他赛[泰索帝)作为二线化疗耐晚期非小细胞肺癌(NSCLC)的疗效和不良反应，方法：23例经病理和(或)细胞学诊断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．接受泰素帝75mg/m^2静滴1小时．第1天．每3周重复。结果：可评价疗效23例中．无完全缓解（CR)，部分缓解(PR）17％(4／23)，稳定(SD)57％(13／23)，进展(PD)26％(6／23)，有效率17％(4／23)；中位生存期9个月，一年生存率39％(9，23)。不良反应主要是血液学毒性，但患者可以耐受。结论：泰素帝草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。     

多西他赛或表皮生长因子受体酪氨酸激酶抑制剂二线治疗晚期非小细胞肺癌的临床观察

目的 观察多西他赛或表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs）二线治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的临床疗效及安全性。 方法 回顾性分析2009年1月至2013年6月接受多西他赛或EGFR-TKIs二线治疗晚期NSCLC患者的临床资料,对符合入组标准的100例进行观察和分析,其中52例接受EGFR-TKIs治疗（TKIs组）,48例接受多西他赛治疗（DOC组）。采用Kaplan-Meier方法计算两组患者的中位无疾病进展生存时间（mPFS） 、中位总生存时间（mOS）,并行Log-rank检验。结果 TKIs组、DOC组患者二线治疗后mPFS分别为6个月、3个月（P=0.021）;mOS分别为16个月、10个月（P=0.068）;客观有效率（ORR）分别为23.1％、6.3％（P=0.038）。DOC组Ⅲ~Ⅳ级白细胞减少、中性粒细胞减少及其引起发热的发生率明显高于TKIs组（P均＜0.001）。结论 临床上对具有EGFR敏感突变潜在临床特征的晚期NSCLC患者进行二线治疗时,EGFR-TKIs比多西他赛治疗能显著延长患者中位无疾病进展生存时间,毒副反应较少,具有更高的安全性。     

多西紫杉醇联合重组人血管内皮抑制素二线治疗晚期非小细胞肺癌

目的：评价多西紫杉醇联合重组人血管内皮抑制素（恩度）二线治疗晚期非小细胞肺癌（ＮＳＣＬＣ）的疗效和毒副反应。方法：采用同期非随机对照方法,共７３例晚期复发的ＮＳＣＬＣ患者入组。２８例患者接受多西紫杉醇联合恩度二线治疗（治疗组）,４５例患者接受多西紫杉醇单药二线治疗（对照组）,每个周期行影像学检查评价疗效。结果：治疗组和对照组的有效率分别为１７.９％和１３.３％（Ｐ＝０.８５０）,疾病控制率分别为６４.３％和５３.３％（Ｐ＝０.３５７）,中位无进展生存期（ＰＦＳ）分别为４个月和３个月（Ｐ＝０.０１５）,中位生存期（ＯＳ）分别为８个月和６个月（Ｐ＝０.０３０）。两组常见的毒副反应是骨髓抑制、脱发、乏力、关节酸痛,治疗组和对照组的差异无统计学意义（Ｐ＞０.０５）。结论：多西紫杉醇联合重组人血管内皮抑制素二线治疗既往化疗失败的晚期ＮＳＣＬＣ,能够提高患者ＰＦＳ和ＯＳ,且毒副反应无明显增加。     

多西紫杉醇联合长春瑞滨二线治疗晚期非小细胞肺癌的临床研究

Objective:To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinorelbine.The chemotherapy included vinorelbine (25 mg/m2) on days 1,5 and docetaxel (60 mg/m2) on day 1.The treatment was repeated every 3 weeks.Patients receiving at least two cycles were evaluated for efficacy and toxicity.Results:Of 48 patients,1 patient achieved complete response and 16 achieved partial response.Overall response rate for all 48 patients was 35.4% (17/48).Main hematologic toxicities included neutropenia (60.4%) and febrile neutropenia (29.2%) and non-hematologic toxicities were mild.Conclusion:The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC.Further studies may confirm these results.     

晚期非小细胞肺癌的二线治疗进展

晚期非小细胞肺癌一线化疗后仅能有一个较短暂的疾病缓解期,绝大部分患者需要进行二线治疗。目前推荐的二线治疗药物主要是多西紫杉醇、培美曲赛和EGFR-TKIs。多西紫杉醇最先确立其二线治疗的地位。培美曲赛通过一项与多西紫杉醇进行随机对照的Ⅲ期研究批准用于晚期NSCLC二线治疗。虽然培美曲赛毒性很轻微,但进一步的临床研究并没有发现高剂量对患者生存有益。EGFR-TKIs靶向治疗是目前研究的热点。吉非替尼和厄洛替尼单药二线治疗具有较好的疗效。吉非替尼与传统化疗对照的研究表明,其疗效不差于多西紫杉醇,且毒性较化疗轻微。厄洛替尼与化疗对照的研究正在进行。其它一些药物不断出现,显示了其在二线治疗的作用,例如口服拓扑替肯和长春氟宁与多西紫杉醇均具有相似的疗效。     

吉西他滨联合异环磷酰胺二线治疗晚期非小细胞肺癌疗效分析

为了观察吉西他滨联合异环磷酰胺方案二线治疗晚期非小细胞肺癌(NSCLC)的疗效及不良反应,选取24例病理或细胞学确诊的晚期NSCLC,经紫杉类联合铂类化疗方案治疗进展的患者,采用吉西他滨1.0 g/m2,静脉滴入,d1、d8;异环磷酰胺1.2 g/m2,静脉滴入,d2～d4,21 d为1个周期,以TAX317研究结果为...     

Docetaxel and non-small cell lung cancer

Docetaxel (Taxotere) is a taxoid used in various tumoral diseases. Its role in metastatic or locally advanced non small cell lung cancer treatment is undeniable. In pretreated patients with metastatic NSCLC, two recent phase III trials have shown an improvement of survival and quality of life for patients receiving docetaxel. In front line treatment, docetaxel administered alone every three weeks or in combination with a platine compound has became a gold standard treatment. Activity of the associations cisplatinium/docetaxel and carboplatin/docetaxel is similar to those reported with previous combinations containing a platine derivative. The weekly schedule of docetaxel and its combination with other well known active drugs in NSCLC such as gemcitabin or vinorelbin deserve further evaluations. Therapeutic options with docetaxel in adjuvant situation in resected NSCLC or in combination with radiation therapy in operable locally advanced NSCLC should be developed in the next future.     

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。     

Antiangiogenic agents as second-line therapy for advanced non-small cell lung cancer

With the approval of the antiangiogenic antibody bevacizumab in non-small cell lung cancer (NSCLC) and other malignancies, the tumor vasculature has emerged as a worthwhile therapeutic target. Second-line therapies have the potential to improve overall survival and quality of life over best supportive care alone. Accordingly, phase II and phase III studies are actively evaluating antiangiogenic treatments in the second-line setting in NSCLC, and results are awaited. Such therapies include antiangiogenic antibodies, small molecule inhibitors, and vascular-disrupting agents. This review will present the current landscape of angiogenesis inhibition in NSCLC, focusing on use as second-line therapy.     

多西他赛联合卡铂治疗晚期非小细胞肺癌的疗效

背景与目的 化疗是治疗晚期非小细胞肺癌的主要方法.本研究旨在分析多西他赛加卡铂治疗晚期非小细胞肺癌的疗效.方法 本组共治疗64例ⅢB、Ⅳ期非小细胞肺癌,采用多西他赛75 mg/m2静脉注射,第1天,卡铂AUC=5静脉注射,第2天.结果 全组总有效率CR PR为42.6%,临床获益率CR PR SD为68.9%,中位生存期14个月,1年生存率45.23%.初治病例1年生存率48.84%,中位生存期14个月;复治病例1年生存率37.89%,中位生存期12个月,两组之间差异有统计学意义(P=0.0233).ⅢB期病例1年生存率44.86%,中位生存期15个月;Ⅳ期病例1年生存率39.75%,中位生存期12个月,两组之间差异有统计学意义(P=0.0354).腺癌、鳞癌患者的疗效差异无统计学意义.主要毒副反应为粒细胞下降、乏力、恶心呕吐及脱发等.结论 多西他赛联合卡铂方案治疗晚期非小细胞肺癌疗效可靠,副反应轻微,可作为晚期非小细胞肺癌的一线和二线治疗方案.     

国产紫杉醇加卡铂治疗晚期非小细胞肺癌的临床研究

目的 探讨紫杉醇加卡铂联合化疗方案对晚期非小细胞肺癌的疗效和毒性反应。方法 78例晚期非小细胞肺癌应用国产紫杉醇150mg/m^2加卡铂300mg/m^2联合方案化疗。结果 58例初治者和20例复治者近期有效率分别为56.9%和35.0%,总有效率51.3%,有4例（5.1%)获CR,中位生存期9.0个月,1年存活率为33.3%,主要不良反应为骨髓抑制及关节或肌肉酸痛。结论 紫杉醇加卡铂对晚期非小细胞肺癌有较好疗效。不良反应可以耐受。     

Docetaxel in advanced non-small cell lung cancer

Based on the survival benefit demonstrated in large randomized clinical trials, docetaxel is approved for the treatment of advanced non-small cell lung cancer (NSCLC) in both the first- and second-line settings. The efficacy of docetaxel in combination with cisplatin is equivalent to some, and superior to other, platinum-based doublets for first-line management of NSCLC, and has a manageable toxicity profile. Carboplatin-based regimens and nonplatinum combinations with docetaxel also have proven efficacy in first-line therapy of patients with advanced NSCLC. Combinations of docetaxel with various novel targeted agents have produced encouraging data in Phase II studies. This article reviews recent studies of docetaxel as a single agent and in combination regimens with cytotoxic and more recent targeted agents in the management of advanced NSCLC.     

Considerations for second-line therapy of non-small cell lung cancer

For patients with advanced non-small cell lung cancer and a good functional status, platinum-based first-line chemotherapy improves quality of life, reduces disease-related symptoms, and improves survival. The addition of bevacizumab to carboplatin and paclitaxel in the first-line setting has been shown to produce a higher response rate and longer progression-free survival and overall survival times than with carboplatin and paclitaxel. Despite these therapies, all patients inevitably experience disease progression. There are currently three agents approved for treating patients who progress after one prior regimen: docetaxel, pemetrexed, and erlotinib. Erlotinib is also indicated for patients who progress after two prior regimens. These agents appear to have similar efficacies in terms of response and overall survival, but have significantly different toxicity profiles. Currently, the choice of agent depends on a number of factors, including the patient's comorbidities, toxicity from previous treatments, the risk for neutropenia, smoking history, and patient preference. A better understanding of prognostic factors in the second-line setting may allow clinicians to better select patients for second-line therapy, and lead to better-designed second-line trials. Patients with a good performance status in second-line trials have a median survival duration of approximately 9 months, and may receive two second-line therapies during the course of their treatment. Several new agents have shown activity in phase II trials, and may be integrated into second-line therapy as single agents or in combination with current agents in the future.     

Phase II study of cisplatin-combined schedules as second-line chemotherapy in patients with non-small cell lung cancer

BACKGROUND: The aim of this study was to evaluate the effectiveness of cisplatin- (CDDP) combined chemotherapy in non-cisplatin pretreated patients with non-small-cell lung cancer (NSCLC). The second cytotoxic drug administered was either etoposide or gemcitabine. First-line treatment was based on paclitaxel combined with either carboplatin or vinorelbine. PATIENTS AND METHODS: Seventy-eight patients with histologically- or cytologically- confirmed NSCLC, having failed front-line treatment, were enrolled. All patients received 80 mg/m2 of cisplatin as second-line treatment, on day 1, repeated every 3 weeks; in 48 patients the second agent was etoposide (120 mg/m2) on days 1, 2 and 3, repeated every 3 weeks and in 30 patients 1 g/m2 of gemcitabine on day 1, repeated every 3 weeks. RESULTS: All patients were evaluable for response and toxicity. No complete responses were observed. Thirteen (16.67%) patients achieved partial response, 42 (53.85%) stable disease and 23 (29.49%) had disease progression. The median duration of response was 4 months (range 2-8+ months), median time to tumor progression (TTP) 5 months (range 2-9 months) and median survival time after starting second-line chemotherapy, 6 months (range 2-9+ months). Toxicity was acceptable: 9 patients presented with nephrotoxicity (11.54%) and 13 (16.67%) with grade 3-4 neutropenia. CONCLUSION: The cisplatin combination as second-line treatment in patients with NSCLC exhibited a notable degree of activity and tumor growth control was evidenced by the 16.67% partial response and 53.85% disease stability.     

Long-term survival after second-line therapy with docetaxel and carboplatin and monthly pamidronic acid in a woman with metastatic non-small cell lung cancer

BACKGROUND: In patients with metastatic non-small cell lung cancer (NSCLC), second-line chemotherapy induces response rates of less than 20% and median survival times between 5 and 8 months. CASE REPORT: In the case described here, a patient with metastatic NSCLC responded with complete remission of the primary tumor and the involved lymph nodes as well as partial remission of bone metastases to a second-line chemotherapy with docetaxel and carboplatin. Since April 2003 (33 months), no tumor progression has been observed. Until present, the patient received monthly infusions of pamidronic acid. CONCLUSION: Our case report indicates that in certain patients with metastatic NSCLC who did not respond to first-line regimens, second-line chemotherapy can induce outstanding tumor response and significantly improve survival. It also indicates that the role of bisphosphonates in the treatment of NSCLC should be further investigated in large clinical trials.