2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer

PURPOSE: An American Society of Clinical Oncology (ASCO) focused update updates a single recommendation (or subset of recommendations) in advance of a regularly scheduled guideline update. This document updates one recommendation of the ASCO Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer (NSCLC) regarding switch maintenance chemotherapy. CLINICAL CONTEXT: Recent results from phase III clinical trials have demonstrated that in patients with stage IV NSCLC who have received four cycles of first-line chemotherapy and whose disease has not progressed, an immediate switch to alternative, single-agent chemotherapy can extend progression-free survival and, in some cases, overall survival. Because of limitations in the data, delayed treatment with a second-line agent after disease progression is also acceptable. RECENT DATA: Seven randomized controlled trials of carboxyaminoimidazole, docetaxel, erlotinib, gefitinib, gemcitabine, and pemetrexed have evaluated outcomes in patients who received an immediate, non-cross resistant alternative therapy (switch maintenance) after first-line therapy. RECOMMENDATION: In patients with stage IV NSCLC, first-line cytotoxic chemotherapy should be stopped at disease progression or after four cycles in patients whose disease is stable but not responding to treatment. Two-drug cytotoxic combinations should be administered for no more than six cycles. For those with stable disease or response after four cycles, immediate treatment with an alternative, single-agent chemotherapy such as pemetrexed in patients with nonsquamous histology, docetaxel in unselected patients, or erlotinib in unselected patients may be considered. Limitations of this data are such that a break from cytotoxic chemotherapy after a fixed course is also acceptable, with initiation of second-line chemotherapy at disease progression.     

Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC)

BACKGROUND: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. PATIENTS AND METHODS: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. RESULTS: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received = 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). CONCLUSIONS: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression.     

替吉奥维持干预在转移性鼻咽癌治疗中的时机优势研究北大核心

目的:通过与转移性鼻咽癌进展后二线治疗模式的生存预后比较,明确转移性鼻咽癌一线治疗后替吉奥(S-1)维持干预治疗的时机优势。方法:一线化疗临床获益的转移性鼻咽癌患者,1∶2分层随机为研究组(维持干预组,S-1维持至疾病进展或不能耐受)和对照组(延迟干预组),评价S-1及时维持干预在改善转移性鼻咽癌整体预后中的时机优势。结果:至2019年5月入组157例患者,中位随访20.2月(8.0~53.1月)。可评价病例143例:维持干预组51例,延迟干预组92例。与延迟干预组比较,S-1维持干预提高转移性鼻咽癌一线化疗后的中位首次无疾病进展生存期(mfPFS)(8.4月vs 16.0月,P<0.001)及全程无疾病进展生存期(mtPFS)(14.8月vs 16.0月,P=0.006);并显著改善患者中位总生存(mOS)(21.1月vs 27.5月,P=0.003);亚组分析,转移性鼻咽癌一线化疗后及时的S-1维持干预与延迟干预比较,S-1维持干预显著延长mtPFS(16.0月vs 14.8月、13.3月,P=0.004)及mOS(27.5月vs 23.4月、19.6月,P<0.001)。维持干预组耐受性良好,不良反应主要表现为1级的皮肤色素沉着、口腔黏膜炎、手足综合征、恶心等,经过方案调整或短期治疗延迟(<2周),患者均可耐受。结论:转移性鼻咽癌一线化疗后及时进行替吉奥维持干预比延迟干预明显改善转移性鼻咽癌患者生存预后,患者耐受性良好。     

Management of Italian Patients With Advanced Non–Small-Cell Lung Cancer After Second-Line Treatment: Results of the Longitudinal Phase of the LIFE Observational Study

Introduction/BackgroundPatients with advanced NSCLC who experience disease progression after second-line therapy might receive further active treatment. LIFE was an Italian cohort multicenter observational study composed of a cross-sectional and a longitudinal phase.Patients and MethodsIn the longitudinal phase, described here, the primary aim was to determine the proportion of patients receiving third-line therapy among those who received second-line active treatment according to clinical practice. The proportion of patients receiving further treatment lines was also estimated.ResultsThe longitudinal phase was conducted between January and August 2012. Of 464 patients who began second-line therapy outside of clinical trials within the baseline evaluation, 56 (12.1%) were still receiving second-line therapy at the end of the observation period and 17 (3.7%) withdrew during or after second-line therapy. Of the remaining 391 patients, 158 (40.4%) received third-line treatment outside of clinical trials: 93 received a third-line chemotherapy and 65 a targeted agent. The main reason for interrupting third-line treatment was disease progression or death. During the same observation period, 25 of 113 patients who completed a third-line therapy received a fourth line of treatment. From diagnosis of NSCLC to the end of observation, biomarkers were tested in 323 patients (59.7%): epidermal growth factor receptor mutations in 315 (58.2%), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations in 83 (15.3%) and Anaplastic lymphoma kinase (ALK) translocation in 84 (15.5%).ConclusionIn Italian clinical practice, the proportion of patients with advanced NSCLC receiving more than 2 treatment lines of therapy is not negligible.     

The role of rituximab in combination with pentostatin or cladribine for the treatment of recurrent/refractory hairy cell leukemia

BACKGROUND: The purine analogs pentostatin and cladribine have revolutionized the treatment of hairy cell leukemia (HCL) with overall responses in greater than 85% of patients and a median progression-free survival of up to 15 years. They continue to be effective at second- and even third-line therapy; however, alternative treatments are needed for patients who are or have become refractory to these agents or whose remissions are shorter with each course of therapy. METHODS: The authors conducted a retrospective review of 8 patients who received pentostatin or cladribine combined concurrently (n = 6 patients) or sequentially (n = 2 patients) with rituximab at second-line therapy (n = 3 patients) and at subsequent lines of therapy (n = 5 patients). Results from a previously reported database of 219 patients with HCL (73 patients who received second-line therapy and 20 patients who received third-line therapy) were used as a historic control group against which to measure benefit. RESULTS: All 8 patients responded to therapy, with 7 complete responses (CRs) (87.5%) and minimal toxicity. All patients who had CRs were negative for minimal residual disease (MRD). At a median follow-up of 29 months (range, 5-39 months) 1 patient developed recurrent disease, and the estimated 2-year recurrence rate was 20% (0% after second-line therapy and 25% after subsequent lines of therapy). In the historic control group, the CR rates were 70% after second-line therapy and 45% after third-line therapy, and the recurrence rates at 2 years were 15% and 33%, respectively. CONCLUSIONS: The combination of purine analogs with rituximab was safe and effective for patients with recurrent and/or refractory HCL, and the current results suggested an added benefit compared with standard treatment.     

培美曲塞在晚期非小细胞肺癌二线及以上治疗中的疗效分析

背景与目的培美曲塞是晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)推荐的标准二线治疗方案之一。目前二线治疗之后如何选择化疗药物尚无标准。本研究旨在观察培美曲塞治疗既往接受过多程治疗的晚期NSCLC的疗效和安全性。方法回顾性分析2005年2月-2009年9月在中国协和医科大学肿瘤医院内科肺癌中心接受培美曲塞单药治疗,且既往接受过1个及以上方案治疗的37例晚期NSCLC的病例资料。结果 37例患者中二线治疗者13例(35.1%),三线及以上治疗者24例(64.9%)。疾病控制率为54.1%,其中1例(2.7%)完全缓解(双肺转移瘤消失),2例(5.4%)部分缓解,17例(45.9%)稳定,12例(32.4%)进展。中位无进展生存期为8.05个月,中位生存时间为19.29个月。毒副反应轻微。结论培美曲塞用于晚期NSCLC二线及以上治疗耐受性较好,并且有生存获益,可推荐作为二线及以上晚期NSCLC患者治疗的选择。     

参一胶囊在晚期非小细胞肺癌维持治疗中的疗效观察

目的 观察晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）一线化疗获益的患者后续参一胶囊维持治疗的疗效与不良反应.方法 初治、晚期NSCLC患者一线化疗最多6个周期后疗效评价无疾病进展的患者随机分组,35例进入观察组,仅接受定期随访观察,34例进入治疗组,接受参一胶囊维持治疗,维持治疗持续到疾病进展或出现患者不能耐受为止.结果 随访过程中治疗组有2例患者退出或失访,治疗组与观察组的疾病进展率分别为53.1％和62.9％,中位无进展生存期分别为6.5个月和6.2个月,差异均无统计学意义（P＞0.05）.在生活质量和免疫功能改善以及疾病进展后接受二线治疗的患者比例方面,治疗组均优于观察组（P＜0.05）.整个维持治疗过程中无治疗相关性死亡.结论 对于晚期NSCLC,一线化疗后继续参一胶囊维持治疗可改善生活质量,提高免疫功能,有利于更多患者接受二线治疗,且安全性良好,值得进一步研究.     

A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: second line taxane-based therapy after first-line epothilone-B analog ixabepilone (BMS-247550) therapy

BACKGROUND: Epothilones and taxanes interfere with microtubule function. Ixabepilone, which is an epothilone-B analog, has activity against taxane-resistant cell lines and as first-line therapy for men with hormone-refractory prostate carcinoma (HRPC). Clinical cross-resistance of ixabepilone and taxanes in HRPC is unknown. METHODS: Records were evaluated retrospectively from patients with HRPC who were treated on a randomized Phase II trial of ixabepilone with or without estramustine and who subsequently received taxane chemotherapy. Posttherapy declines in prostate-specific antigen (PSA) levels and time to PSA progression were defined by consensus criteria. The median survival was evaluated by using the Kaplan-Meier method. RESULTS: Forty-nine patients who received ixabepilone with estramustine (28 patients) or without estramustine (21 patients) subsequently received second-line taxane therapy. Second-line PSA declines > or = 50% were achieved by 51% of patients (95% confidence interval [95% CI], 33-66%). Second-line PSA declines > or = 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline > or = 50% with ixabepilone, compared with 33% of patients (95% CI, 13-59%) who did not (P = 0.08). Patients who discontinued first-line ixabepilone treatment for disease progression were less likely to achieve a PSA decline > or = 50% in response to second-line, taxane-based therapy compared with patients who discontinued for toxicity or patient preference (36% vs. 71%; P = 0.01). CONCLUSIONS: Second-line taxane chemotherapy after ixabepilone resulted in a substantial frequency of PSA declines. Although patients with ixabepilone-refractory disease were less likely to respond to second-line taxane chemotherapy, 36% did achieve a PSA response. These findings were consistent with incomplete clinical cross-resistance between the taxanes and the epothilones.     

Second-line chemotherapy in gastric cancer following S-1 with CPT-11 chemotherapy performed as clinical trial

We previously conducted a phase I/II study of irinotecan (CPT-11) combined with S-1 as first-line chemotherapy for metastatic advanced gastric cancer. In the present study,second-line chemotherapy was given to 32 of 44 patients whose disease became refractory to this first-line treatment. Overall survival time of the patients given second-line chemotherapy was significantly longer than that of patients not given such therapy (444 days vs. 230 days, p = 0.013). The response rate to second-line chemotherapy was 13% (4/32). Survival time of patients who responded to second-line chemotherapy was significantly longer than that of non-responders. Second-line chemotherapy may produce a better clinical response in patients who have progressive disease during first-line chemotherapy. Overall survival time and time to progression after second-line chemotherapy did not significantly differ between patients who received second-line chemotherapy regimens including S-1 and those who received regimens not including S-1.     

Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network.

PURPOSE: To compare the benefit of maintenance rituximab therapy versus rituximab re-treatment at progression in patients with previously treated indolent non-Hodgkin's lymphoma. PATIENTS AND METHODS: Between June 1998 and August 2002, 114 patients who had received previous chemotherapy for indolent non-Hodgkin's lymphoma were treated with a standard 4-week course of rituximab. Patients with objective response or stable disease were randomly assigned to receive either maintenance rituximab therapy (standard 4-week courses administered at 6-month intervals) or rituximab re-treatment at the time of lymphoma progression. The duration of rituximab benefit was measured from the date of first rituximab treatment until the date other treatment was required. RESULTS: Ninety (79%) of 114 patients had objective response or stable disease after initial rituximab treatment, and were randomly assigned to treatment. Progression-free survival was prolonged in the maintenance group (31.3 v 7.4 months; P = .007). Final overall and complete response rates were higher in the maintenance group. Duration of rituximab benefit was similar in the maintenance and re-treatment groups (31.3 v 27.4 months, respectively). More maintenance patients remain in continuous remission, and more are currently in complete remission. Both treatment approaches were well tolerated. CONCLUSION: In patients who have objective response or stable disease with single-agent rituximab therapy, duration of rituximab benefit is substantially prolonged with either scheduled maintenance treatment or rituximab re-treatment at the time of progression. At present, the magnitude of benefit with either approach appears similar. However, additional follow-up of this trial is required, and completion of phase III randomized trials is necessary to definitively answer this question.     

Second-Line Capecitabine and Oxaliplatin Combination for Gemcitabine-Resistant Advanced Pancreatic Cancer

Background: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin 130 mg/m2 and capecitabine 1000 mg/m2 twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2.     

对比EGFR-TKIs治疗EGFR突变状态未明晚期NSCLC疗效研究

目的探讨对比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)一线、维持及二线治疗EGFR突变状态未明晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC)的疗效。方法回顾性分析接受EGFR-TKIs治疗的57例EGFR突变状态未明晚期NSCLC,按照接受EGFR-TKIs治疗的时机分为EGFR-TKIs治疗一线组(19例)、维持组(18例)和二线组(20例),按照RECIST标准进行疗效评价。结果一线组、维持组和二线组客观有效率(52.6%vs 38.9%vs 35.0%,P=0.098)、中位无进展生存期(4.0月vs 7.8月vs 2.2月,P=0.417)差异无统计学意义,但一线组患者总生存期较维持组和二线组差(8.7月vs 20.0月vs 19.1月,P=0.009)。结论 EGFR突变状态未明晚期NSCLC EGFR-TKIs一线、维持和二线治疗的客观有效率和中位无进展生存期相似,但EGFR-TKIs一线治疗总生存期较短,建议EGFR-TKIs用于维持或二线治疗EGFR突变状态未明晚期NSCLC。     

Comparison of Single Agent Gemcitabine and Docetaxel in Second-Line Therapy for Advanced Stage Non-Small Cell Lung Cancer in a University Hospital in Turkey

Purpose: To compare the efficacy and toxicity of gemcitabine versus docetaxel in a second-line setting of nonsmall cell lung cancer (NSCLC) patients previously treated with platin-based combination chemotherapy. Materials and Methods: We retrospectively evaluated the medical records of 57 patients treated with single agent gemcitabine or docetaxel in second-line setting of advanced NSCLC who received one prior platinumbased therapy. Results: The mean age was 56.7±8.39 years with 55 ( 96.5%) males and two (3.5%) females. Forty of them received docetaxel and 17 gemcitabine. The mean number of chemotherapy cycles was 6.8±4.0 in the gemcitabine group, while it was 4.6±3.0 in the docetaxel group. Overall response rates were 8% and 12% (P=0.02) for gemcitabine and docetaxel, respectively. The median survival time was 22 versus 21 months for gemcitabine and docetaxel, respectively. The median times to progression were 8 and 5 months. There was no difference between the two groups in terms of incidence of adverse affects (40% vs 47.1%). All of the hematological side effects were grade 1/2. No major toxicity was encountered necessitating stopping the drug for either group. Conclusions: Treatment with gemcitabine demonstrated clinically equivalent efficacy with a significantly improved safety profile compared with those receiving docetaxel in the second-line setting for advanced NSCLC in this study. Based on these results, treatment with gemcitabine should be considered a standard treatment option for second-line NSCLC.     

Current status of second-line therapy for metastatic colorectal cancer

Decisions regarding the optimal systemic therapy for patients with metastatic colorectal cancer (CRC) have become more complex with the identification and development of multiple effective agents for this disease. Multiple treatment options are now available in the second-line setting for patients with metastatic CRC who have progressed despite prior chemotherapy. The exact choice of second-line therapy depends on the first-line treatment that was administered. Irinotecan as a salvage therapy for patients with metastatic CRC who have progression following front-line 5-fluorouracil (5-FU)-based therapies was confirmed in a number of phase II/III studies. Many patients who received irinotecan/5-FU-based therapy as first-line treatment benefit from the combination of oxaliplatin and 5-FU/leucovorin (FOLFOX) in terms of response, time to progression, and relief of tumor-related symptoms. Other considerations include the integration of targeted therapies into chemotherapy regimens. The results of a randomized phase II trial have demonstrated that the addition of cetuximab to irinotecan in patients with irinotecan-resistant tumors represents another active treatment option for these patients. The activity of bevacizumab as part of second-line therapy is currently under investigation and results from phase III trials are expected within the next year. In summary, the availability of 5 drugs that are active in CRC provides us, for the first time, with choice--and dilemma--regarding optimal second-line therapy in patients with metastatic CRC.     

Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support.

PURPOSE: We performed a retrospective review to determine predictive and prognostic factors in patients with metastatic breast cancer who received induction therapy, and, if they responded to treatment, high-dose chemotherapy. PATIENTS AND METHODS: Patients with metastatic breast cancer received induction therapy with doxorubicin, fluorouracil, and methotrexate (AFM). Partial responders then received immediate high-dose chemotherapy, whereas those who achieved complete remission were randomized to immediate or delayed high-dose chemotherapy with hematopoietic stem-cell support. We performed a retrospective review of data from these patients and used Cox proportional hazards regression models for analyses. RESULTS: The overall response rate for the 425 patients enrolled was 74% (95% confidence interval, 70% to 78%). Multivariate analysis of data from all 425 patients revealed that positive estrogen receptor status (P =.0041), smaller metastatic foci ( 2 cm) (P =. 0165), a longer disease-free interval from initial diagnosis to diagnosis of metastases ( 2 years) (P =.0051), and prior treatment with tamoxifen (P =.0152) were good prognostic signs for overall survival. Patients who had received prior adjuvant therapy (P =.0001) and those who developed liver metastases (P =.0001) had decreased long-term survival. In the subgroup of responders to AFM induction, multivariate analysis showed that those with visceral metastases did less well (P =.0006), as did patients who had received prior adjuvant therapy (P =.0023). However, those who had received tamoxifen therapy in the adjuvant setting did better (P =. 0143). CONCLUSION: The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive-patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.     

Comprehensive Genomic Profiling of Circulating Tumor DNA in Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of a Real-World Healthcare Claims Database

We used a real-world database (GuardantINFORM^TM) to analyze the treatment choices for patients with mCRC who underwent next-generation sequencing of circulating tumor DNA (ctDNA) using a commercially available test (Guardant360^®) after first- or second-line therapy. From 18,875 patients with claims for CRC, 1064 had confirmed metastatic disease and sufficient histories for analysis (median age 59 years, 44.8% female, 44.5% left-sided). ctDNA was detectable for 997/1064 (93.7%) patients. Clinically actionable molecular profiles were present for 507/1064 (47.7%) patients, including those who had not received targeted therapy in the previous line (410/926, 44.3%). Second- or third-line targeted therapies were administered to 338/1064 patients (31.8%) and were considered matched for 193/338 (57.1%) patients. Therapies administered after testing were informed by the ctDNA results in 56.7% of patients overall (603/1064). Time to treatment discontinuation was most favorable for patients with a clinically actionable ctDNA profile who received matched therapy. This analysis demonstrates the real-world clinical value of plasma-based comprehensive genomic profiling for selecting appropriate molecular-targeted therapies in mCRC patients with disease progression after first- or second-line therapy.     

局部晚期非小细胞肺癌维持化疗的疗效评价

目的:本研究旨在评价初次放化疗有效的局部晚期非小细胞肺癌患者接受维持化疗的疗效.方法:120例ⅢA和ⅢB期非小细胞肺癌患者接受4个周期的诱导化疗联合放疗后,将其中治疗有效的63例患者随机分入维持化疗组(33例患者接受长春瑞滨维持化疗,20 mg/m~2 第1和第8天,以28 d为1个化疗周期)和对照组(30例患者只接受观察,不给予维持化疗),评估这两组患者的疗效、生存期和不良反应.结果:维持化疗组的中位疾病进展时间较对照组延长(分别为8.5和5.0个月),差异有统计学意义(P＜0.05);维持化疗组的1年和2年生存率分别为66.7%和36.4%,对照组为60.7%和32.1%,差异均无统计学意义(P＞0.05).结论:诱导化疗有效的局部晚期非小细胞肺癌患者接受长春瑞滨维持化疗后,可延长疾病进展时间,但对生存期无影响.     

Selection of a patient subgroup with advanced esophageal squamous carcinoma who could benefit from second-line chemotherapy

Despite first-line therapy, most patients with advanced esophageal squamous cell carcinoma (ESCC) experience disease progression and may become eligible for second-line chemotherapy. Although commonly used, the role of salvage chemotherapy in patients with recurrent or metastatic ESCC has not yet been established. We analyzed 53 patients who had received second-line chemotherapy after the failure of cisplatin-based combination chemotherapy with or without radiotherapy as first-line therapy in ESCC between March 2000 and June 2008. Median progression-free survival (PFS) and overall survival (OS) for second-line chemotherapy were 2.4 and 5.2 months, respectively, with an overall response rate of 18.9%. In multivariate analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 or more and PFS under first-line therapy <4 months were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: 0 = good; 1 = intermediate, and 2 = poor. The median OS for the good, intermediate, and poor prognostic groups were 11.2, 4.5 and 4.3 months, respectively (p < 0.001). The good prognostic group showed better OS than the intermediate or poor groups (p < 0.001). Second-line chemotherapy may be beneficial for OS in ESCC patients with ECOG PS 0-1 and PFS under first-line therapy ≥4 months.     

Docetaxel in second-line treatment of non-small-cell lung cancer

The survival and quality-of-life benefits of docetaxel in the second-line treatment of non-small-cell lung cancer (NSCLC) are supported by two phase III trials: TAX 317 and TAX 320. In TAX 317, 204 patients were randomized to receive either docetaxel 100 mg/m2 (D100) or 75 mg/m2 (D75) intravenously every 3 weeks, or best supportive care (BSC). Median survival was 9.0 months with D75 versus 4.6 months for BSC (P = 0.016); 1-year survival was 40% for D75 versus 16% for BSC (P = 0.016). Quality-of-life analysis showed significant improvement in several disease-related symptoms in patients who received docetaxel. TAX 320 was a supportive trial, in which 373 patients were randomized to receive D100, D75, or the control treatment of vinorelbine or ifosfamide (V/I). The partial response rate was 12% with D100 and 8% with D75 versus 1% with V/I (D100, P = 0.001 and D75, P = 0.036). Median response duration was 7+ months. One-year survival was 32% with D75 and 19% with V/I (P = 0.025). In TAX 320, prior paclitaxel exposure had no bearing on the response rate and survival advantage of second-line treatment with docetaxel. Response rates to docetaxel were equivalent in the cohort of patients who had received prior paclitaxel (10.5%) and the group of patients who had not received prior paclitaxel (8.5%). Furthermore, 1-year survival rates for patients with no prior paclitaxel therapy were 33% (D75) and 20% (V/I); 1-year survival rates for patients who had received prior paclitaxel were 30% (D75) and 17% (V/I). Docetaxel at a dose of 75 mg/m2 every 3 weeks offers a clinically meaningful improvement in response rate, time to progression, survival, and quality of life in the second-line treatment of advanced NSCLC. Furthermore, prior paclitaxel did not decrease the likelihood of response to docetaxel, nor did it lessen the survival advantage seen with docetaxel.     

Is there a role for maintenance therapy in non-small-cell lung cancer? An emerging issue

Standard treatment of advanced non-small-cell lung cancer consists of platinum-based (doublet) polychemotherapy. The treatment should last for a maximum of four to six cycles. Several randomized clinical trials and some meta-analyses showed that a longer duration of treatment does not lead to an increase in survival. Recent data with new-generation agents (chemo- or targeted therapies) suggest that a maintenance treatment until progression of disease in patients with response or stable disease after the first cycles of induction (platinum-based) chemotherapy confers an advantage in time-to-progression or even overall survival (with pemetrexed) compared with no maintenance treatment. The advent of new agents and the better selection of patients according to histology or mutation of specific tyrosine kinase receptors (e.g., EGF receptor) seems to increase the therapeutic options and improve the prognosis in the advanced disease setting. The paradigm of the duration of therapy in advanced lung cancer appears to change from the use of second-line treatment only at progression of disease to an early introduction of an alternative (second-line) therapy as consolidation and chronic phase of maintenance.