Erlotinib in non-small cell lung cancer: a review

Erlotinib (Tarceva?, OSI-774; Pfizer, Inc.) is an orally-active, targeted inhibitor of the epidermal growth factor receptor (EGFR/HER1), which is part of a key regulatory pathway in cancer. Patients with advanced, incurable non-small cell lung cancer (NSCLC) may derive a clinical benefit from first- and second-line chemotherapy, but third-line treatment with available cytotoxic agents is not effective. Remarkably, EGFR/HER1 antagonists have demonstrated activity as second- and even third-line treatment for this disease. Erlotinib is the first of this novel class of drug to demonstrate a statistically significant and clinically relevant difference in overall survival, progression free survival and time to disease related symptoms (cough, pain, shortness of breath) compared with treatment with best supportive care in patients who have failed standard first- or second-line chemotherapy. This paper reviews the pharmacology, preclinical and clinical data to support the use of erlotinib in NSCLC.     

Erlotinib in non-small-cell lung cancer

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting. Erlotinib is well tolerated (with common toxicities including rash and diarrhoea) when administered at a standard oral daily dose of 150 mg. Further investigations are ongoing to contribute to our understanding of the role of erlotinib in NSCLC treatment.     

Erlotinib in non-small-cell lung cancer

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting. Erlotinib is well tolerated (with common toxicities including rash and diarrhoea) when administered at a standard oral daily dose of 150 mg. Further investigations are ongoing to contribute to our understanding of the role of erlotinib in NSCLC treatment.     

Small molecules with EGFR-TK inhibitor activity

Specific and reversible EGFR tyrosine kinase inhibitors (TKI) such as gefitinib and erlotinib are clinically active in advanced or metastatic NSCLC and both are approved in various countries for the treatment of patients that failed prior chemotherapy. Erlotinib has also prolonged survival in pancreatic cancer patients when added to gemcitabine and regulatory approval in this disease is being sought. Additional promising activity has been seen in other tumor types, such as ovarian cancer or head and neck malignancies, and phase III trials in these malignancies are ongoing or planned. Despite these successes, these agents have exhibited anecdotal or modest activity when used as single agents in unselected patients with various other tumor types. We have learned that the clinical development of these agents is far from simple and we need to better understand biological and clinical criteria for patient selection and how to best use the different available agents. The recent discovery of EGFR mutations and the potential identification of other markers that might predict patient response could help to optimize the use of these agents in the future. Irreversible EGFR inhibitors, dual EGF/HER2 and pan-ErbB receptor inhibitors may have greater antitumor activity although the tolerance of these compounds compared to specific EGFR TKIs needs further characterization. HER2 specific TKIs are also in development. Lapatinib, a dual EGFR/HER2 TK inhibitors, is particularly promising in breast cancer. Newer agents, such as BMS-599626, have recently entered into the clinic. In addition to the use of these agents as single agents, many clinical studies are addressing the role of combining them with hormonal agents, biological agents or chemotherapy.     

Erlotinib: a new therapeutic approach for non-small cell lung cancer

Although treatment with cytotoxic agents has produced modest survival improvement in patients with stage III and IV non-small cell lung cancer (NSCLC), it appears that a plateau has been reached with currently available chemotherapeutic regimens. Increasing knowledge regarding the properties of malignant neoplasms has identified a number of potential therapeutic targets. The epidermal growth factor receptor (EGFR) is one of these targets. Preclinical models have revealed that tumour growth can be inhibited by monoclonal antibodies directed against EGFR and EGFR-specific tyrosine kinase inhibitors. Erlotinib (Tarceva?; OSI Pharmaceuticals, Genentech and Roche), a quinazoline derivative with good oral absorption, is one of several EGFR tyrosine kinases that has been studied in clinical trials. In a Phase I study, mild diarrhoea and mild rash were the most common toxicities. At a dose of 200 mg/day, diarrhoea was the dose-limiting toxicity. The observation that EGFR overexpression is relatively common in NSCLC led to a Phase II trial of erlotinib at the maximum-tolerated dose (150 mg/day) in previously treated NSCLC patients. Erlotinib produced a 12% response rate and there was no apparent relationship between response and tumour EGFR levels. More recent reports suggest that patients who develop a rash have higher responses. Based on its single agent activity, erlotinib has been evaluated in two Phase III trials which compared erlotinib plus chemotherapy to chemotherapy alone in previously untreated NSCLC patients. Erlotinib has also been compared to placebo in a Phase III trial which was limited to advanced stage NSCLC patients whose disease had progressed after two previous chemotherapy regimens. The optimum use of erlotinib in NSCLC will be determined by the results of the completed and future Phase III trials.     

Erlotinib: a new therapeutic approach for non-small cell lung cancer

Although treatment with cytotoxic agents has produced modest survival improvement in patients with stage III and IV non-small cell lung cancer (NSCLC), it appears that a plateau has been reached with currently available chemotherapeutic regimens. Increasing knowledge regarding the properties of malignant neoplasms has identified a number of potential therapeutic targets. The epidermal growth factor receptor (EGFR) is one of these targets. Preclinical models have revealed that tumour growth can be inhibited by monoclonal antibodies directed against EGFR and EGFR-specific tyrosine kinase inhibitors. Erlotinib (Tarceva trade mark; OSI Pharmaceuticals, Genentech and Roche), a quinazoline derivative with good oral absorption, is one of several EGFR tyrosine kinases that has been studied in clinical trials. In a Phase I study, mild diarrhoea and mild rash were the most common toxicities. At a dose of 200 mg/day, diarrhoea was the dose-limiting toxicity. The observation that EGFR overexpression is relatively common in NSCLC led to a Phase II trial of erlotinib at the maximum-tolerated dose (150 mg/day) in previously treated NSCLC patients. Erlotinib produced a 12% response rate and there was no apparent relationship between response and tumour EGFR levels. More recent reports suggest that patients who develop a rash have higher responses. Based on its single agent activity, erlotinib has been evaluated in two Phase III trials which compared erlotinib plus chemotherapy to chemotherapy alone in previously untreated NSCLC patients. Erlotinib has also been compared to placebo in a Phase III trial which was limited to advanced stage NSCLC patients whose disease had progressed after two previous chemotherapy regimens. The optimum use of erlotinib in NSCLC will be determined by the results of the completed and future Phase III trials.     

Evaluation of erlotinib in advanced non-small cell lung cancer: impact on the budget of a U.S. health insurance plan

BACKGROUND: Lung cancer is the most common non-skin cancer and the leading cause of cancer death among men and women in North America. More than half of all patients diagnosed with lung cancer are diagnosed with advanced disease. Most cases of lung cancer are non-small cell lung cancer (NSCLC). Erlotinib monotherapy is indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least 1 prior chemotherapy regimen. OBJECTIVE: To assess the budgetary impact, from the health plan perspective, of covering erlotinib for treating patients with NSCLC stage IIIb/IV who have failed at least 1 prior chemotherapy regimen. METHODS: An Excel-based model was developed to evaluate costs for U.S. Food and Drug Administration-approved and National Comprehensive Cancer Network guideline-recommended treatment options for second- and third-line NSCLC from the perspective of a U.S. health insurer. In particular, the model compares a formulary with erlotinib and a formulary without erlotinib, including the costs of treatment, drug administration, and adverse effects. The incidence of advanced NSCLC is based on the Surveillance, Epidemiology, and End Results Cancer Registry and adverse effects related to treatment (all agents) in published results of clinical trials. Drug and treatment costs were obtained from publicly available sources in 2005. RESULTS: The base case considers a health plan of 500,000 enrollees. Assuming that erlotinib comprises 30% of second-line treatments and 90% for third-line, total costs of treating stage IIIb/IV NSCLC patients over 1 year are Dollars 382,418 with erlotinib and Dollars 380,968 without erlotinib (difference: Dollars 1,450; 90% confidence interval, -Dollars 61,376 to Dollars 29,855), less than Dollars 0.01 per member per month (PMPM) in 2005. Erlotinib direct cost is offset by reductions in standard chemotherapy-related infusion costs and adverse events. CONCLUSIONS: Based on the analysis, the inclusion of erlotinib on a formulary appears to have a relatively small impact on the annual health care budget or PMPM expenditures if it is used consistent with the product label indications.     

Epidermal growth factor receptor inhibitors: a new prospective in the treatment of lung cancer

Lung cancer is the leading cause of death worldwide. Current treatment modalities, including chemotherapy, radiotherapy and surgery, provide only limited improvement in the natural course of this disease. Therefore, the development of new therapeutic strategies is highly awaited. This review focuses on recent achievements on a novel class of anticancer drugs targeting the EGFR (Epidermal Growth Factor Receptor). The EGFR family is a group of four structurally similar growth factor receptors with tyrosine-kinase activity (EGFR, HER2/neu, ErbB-3, ErbB-4), which dimerize upon binding with a number of ligands, including EGF (Epidermal Growth Factor) and TGF (Transforming Growth Factor), allowing downstream transduction of mitogenic signals. Overexpression of EGFR and HER2 is frequently found in non-small-cell lung cancer (NSCLC), which accounts for over 80% of all malignant lung tumors, and has been associated with a worse clinical outcome. New agents developed to inhibit EGFR function include monoclonal antibodies and small-molecule receptor tyrosine-kinase inhibitors. In this review, results of most recent clinical with EGFR inhibitors including monoclonal antibodies, such as Trastuzumab (Herceptin), IMC-C225 (Cetuximab) and others (ABX-EGF, EMD 72000), and tyrosine-kinase inhibitors, such as ZD1839 (Gefitinib, Iressa), OSI-774 (Erlotinib, Tarceva) and others (CI-1033, GW2016), are summarized. In particular, final results of phase II (IDEAL 1 and 2) and III (INTACT 1 and 2) studies of ZD1839 are reported. In IDEAL trials (ZD1839 single agent in patients pre-treated with chemotherapy) there was clear evidence of tumor regression, symptoms improvement and overall clinical benefit, whereas in the two INTACT trials (ZD1839 in combination with standard platinum-based chemotherapy in chemo-naive patients) ZD1839 did not improve either survival or other clinical endpoints. Possible explanations for these contradictory results and future perspectives are discussed.     

Sequential treatment strategy for malignant pleural effusion in non-small cell lung cancer with the activated epithelial grow factor receptor mutation

With the advent of molecularly targeted therapy, it is necessary to reconsider the strategy for malignant pleural effusion in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The aim of this study was to evaluate the efficacy of a two-line sequential treatment strategy in this patient subgroup. First-line treatment was gefitinib (250?mg/day) until disease progression. Second-line treatment was thoracoscopic talc pleurodesis followed by chemotherapy. Primary endpoints were the overall response and progression-free survival rates after first-line treatment, and the overall survival rate after first- and second-line treatment. Secondary endpoints were the success rate of thoracoscopic talc pleurodesis and gefitinib toxicity. Among the 76 patients enrolled, 61 (80%) were female and the median age was 62 years. The overall response rate after first-line treatment was 92.1% and median progression-free survival was 15 months. The success rate for thoracoscopic talc pleurodesis in 33 patients was 94%. Median follow-up was 35 months. Median overall survival was 39 months. The 1- and 3-year overall survival rates were 86.4% and 46.1%, respectively. The two-line sequential treatment strategy enhanced survival. These preliminary findings provide an insight into novel therapeutic models for malignant pleural effusion in NSCLC harbouring EGFR mutations.     

Spotlight on Gefitinib in Non-Small-Cell Lung Cancer

Gefitinib (Iressa), the first commercially available epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, is indicated in the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). However, approved uses differ between countries; in most markets, gefitinib is approved for third-line use only (e.g. the US, Canada and Switzerland), although in some it is approved for both second- and third-line use (e.g. Japan and Australia) and, additionally, in patients considered unsuitable for chemotherapy (e.g. Indonesia and the Philippines). Few third-line treatment options exist for patients with inoperable advanced NSCLC who have failed both docetaxel and platinum-based chemotherapy regimens. Gefitinib represents a significant advance in the treatment of this population; a once-daily oral dosage of 250 mg/day was well tolerated, produced objective tumour responses and disease stabilization, and improved disease-related symptoms and quality of life. It also produced overall survival outcomes that compared favorably with historical outcomes in a similar group of patients treated with three or four different chemotherapy regimens. These findings have been supported by observations from a global compassionate-use program. Ongoing or planned clinical trials are designed to confirm and/or further define the role of the drug in the above and other clinical settings. Preliminary data demonstrate the presence of activating mutations in EGFR-TK among patients whose disease was highly responsive to treatment with gefitinib, although such mutations have not been correlated to all patients who benefit from the drug. Further studies are needed to fully elucidate the clinical implications of EGFR mutations and to identify patients likely to benefit from EGFR-targeted therapy.     

Recent advances in targeted therapy for non-small cell lung cancer

Non-small-cell lung cancer (NSCLC) is characterized by wide molecular heterogeneity. In recent years, novel agents that target specific, aberrant molecular pathways in NSCLC have been under rigorous evaluation. Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, improves survival for advanced NSCLC patients who progressed following one or two prior chemotherapy regimens. Novel molecular predictive markers, such as EGFR mutations and gene amplification, are at present under evaluation to select patients for therapy with erlotinib. Another area of progress is the recent demonstration that bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), extended survival when administered in combination with chemotherapy for patients with non-squamous NSCLC. Promising anticancer activity has also been noted with agents that inhibit the VEGF receptor tyrosine kinase in patients with advanced NSCLC. Inhibitors of the proteosomal complex, histone deacetylase, mammalian target of rapamycin pathway, and other growth factor receptor-mediated signaling are under investigation for treatment of NSCLC. These developments have paved the way for a new era of tailor-made therapies based on clinical or molecular/genetic profiles in the treatment of NSCLC. This article reviews the recent advances in targeted therapy of advanced NSCLC.     

Recent advances in targeted therapy for non-small cell lung cancer

Non-small-cell lung cancer (NSCLC) is characterized by wide molecular heterogeneity. In recent years, novel agents that target specific, aberrant molecular pathways in NSCLC have been under rigorous evaluation. Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, improves survival for advanced NSCLC patients who progressed following one or two prior chemotherapy regimens. Novel molecular predictive markers, such as EGFR mutations and gene amplification, are at present under evaluation to select patients for therapy with erlotinib. Another area of progress is the recent demonstration that bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), extended survival when administered in combination with chemotherapy for patients with non-squamous NSCLC. Promising anticancer activity has also been noted with agents that inhibit the VEGF receptor tyrosine kinase in patients with advanced NSCLC. Inhibitors of the proteosomal complex, histone deacetylase, mammalian target of rapamycin pathway, and other growth factor receptor-mediated signaling are under investigation for treatment of NSCLC. These developments have paved the way for a new era of tailor-made therapies based on clinical or molecular/genetic profiles in the treatment of NSCLC. This article reviews the recent advances in targeted therapy of advanced NSCLC.     

Reviewing the safety of erlotinib in non-small cell lung cancer

Importance of the field: Erlotinib, a potent inhibitor of EGFR activity, is approved as a monotherapy for the treatment of advanced NSCLC and in combination with gemcitabine for advanced pancreatic cancer. The oral administration and manageable toxicity of erlotinib, along with its similar efficacy to chemotherapy, make it an important option as either maintenance therapy or in second-/third-line for patients with NSCLC who have previously received first-line chemotherapy. It is also an emerging option in other treatment settings in NSCLC.

Areas covered in this review: This review summarizes safety data from major clinical trials of erlotinib in patients with advanced NSCLC, as well as post-marketing data obtained in the 5 years since this drug was first approved.

What the reader will gain: An understanding of the common toxicities expected with erlotinib in patients with advanced NSCLC.

Take home message: Erlotinib is a well-tolerated treatment option for patients with advanced NSCLC. The main adverse events of rash and diarrhea are typically mild or moderate in severity, and rarely lead to treatment withdrawal. When necessary, rash and diarrhea can be easily managed prophylactically, by active intervention or through dose reduction.     

非小细胞肺癌靶向治疗新药——厄洛替尼

厄洛替尼是一种口服、高选择性、可逆的表皮生长因子受体(EGFR)酪氨酸激酶(TK)抑制剂,它通过抑制EGFR-TK的自磷酸化反应,抑制信号转导,从而达到抑制肿瘤生长作用。一项Ⅲ期安慰剂对照临床研究结果表明,厄洛替尼每日口服150 mg单药治疗,可显著延长晚期复发性非小细胞肺癌(NSCLC)病人的生存期、延缓疾病进展和症状恶化,且耐受性较好,最常见的不良反应为皮疹和腹泻。本文对厄洛替尼的药动学和药效学特性、临床疗效和药物相互作用以及难治性晚期NSCLC病人的耐受性等作一综述。     

Chemotherapy versus palliative care in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the world's leading cause of cancer death and about 75% of all patients have advanced disease incurable with localized treatments (surgery and radiotherapy) alone. The aims of therapy in these are palliation of symptoms and extension of life. A substantial body of evidence has emerged in the last 15 years which shows that cisplatin-based combination chemotherapy prolongs life in advanced NSCLC. This evidence, which was well summarized in a major meta-analysis published in 1995, indicated that the degree of impact on survival is modest. Hence the balance between survival benefit and treatment-related toxicity is crucial in all considerations of chemotherapy in this disease. More recently this balance has been altered by considerable progress in the reduction of treatment-related toxicity and by documentation of lung cancer symptom palliation by effective chemotherapy. In 1999 a randomized trial of mitomycin, ifosfamide and cisplatin versus palliative care in 351 patients demonstrated a significant survival advantage for those receiving chemotherapy, which did not compromise their quality of life. This review looks forward to further progress employing newer agents both as first- and second-line chemotherapy in advanced NSCLC.     

Molecularly-targeted therapies for non-small cell lung cancer

Targeting cell-signalling pathways that confer survival advantage to cancer cells has become a major focus of investigation for the treatment of various malignancies. Non-small cell lung cancer (NSCLC), a disease with wide molecular heterogeneity, has become a main testing ground for the evaluation of various targeted agents. Inhibition of the epidermal growth factor pathway with erlotinib results in improved survival and symptom control for patients with advanced NSCLC who progressed following one or two prior chemotherapy regimens. Gefitinib, the first epidermal growth factor receptor (EGFR) inhibitor to be approved by the FDA, failed to demonstrate survival advantage over placebo in a large Phase III trial for patients with advanced NSCLC. The results of this study have raised several important clinical and biological issues that may be relevant for the development of other targeted agents. Recent identification of mutations in the ATP-binding pocket of the EGFR is the first step towards proper patient selection for therapy with an EGFR tyrosine kinase inhibitor. In addition, predictive potential has also been seen with EGFR gene amplification. It is unclear whether monoclonal antibodies against the EGFR may be active independent of the EGFR mutation, as the site of action is different from tyrosine kinase inhibitors. A recent randomised clinical trial that combined the antiangiogenic agent bevacizumab with chemotherapy has demonstrated survival advantage over chemotherapy alone for certain subsets of patients with advanced NSCLC. The exciting results of this study represent an important advance in the treatment of patients with advanced NSCLC.     

Molecularly-targeted therapies for non-small cell lung cancer

Targeting cell-signalling pathways that confer survival advantage to cancer cells has become a major focus of investigation for the treatment of various malignancies. Non-small cell lung cancer (NSCLC), a disease with wide molecular heterogeneity, has become a main testing ground for the evaluation of various targeted agents. Inhibition of the epidermal growth factor pathway with erlotinib results in improved survival and symptom control for patients with advanced NSCLC who progressed following one or two prior chemotherapy regimens. Gefitinib, the first epidermal growth factor receptor (EGFR) inhibitor to be approved by the FDA, failed to demonstrate survival advantage over placebo in a large Phase III trial for patients with advanced NSCLC. The results of this study have raised several important clinical and biological issues that may be relevant for the development of other targeted agents. Recent identification of mutations in the ATP-binding pocket of the EGFR is the first step towards proper patient selection for therapy with an EGFR tyrosine kinase inhibitor. In addition, predictive potential has also been seen with EGFR gene amplification. It is unclear whether monoclonal antibodies against the EGFR may be active independent of the EGFR mutation, as the site of action is different from tyrosine kinase inhibitors. A recent randomised clinical trial that combined the antiangiogenic agent bevacizumab with chemotherapy has demonstrated survival advantage over chemotherapy alone for certain subsets of patients with advanced NSCLC. The exciting results of this study represent an important advance in the treatment of patients with advanced NSCLC.     

阿法替尼治疗晚期非小细胞肺癌的疗效和安全性观察

目的：观察第二代表皮生长因子受体酪氨酸激酶抑制剂（EGFR －TKIs）阿法替尼治疗晚期非小细胞肺癌（NSCLC）的疗效和安全性。方法纳入37例经病理学或细胞学确诊的Ⅳ期非小细胞肺癌（NSCLC）患者。一线表皮生长因子受体（EGFR）突变患者10例,给予阿法替尼每日40 mg 口服;二线及以上患者27例,其中2例二线鳞癌患者给予阿法替尼每日40 mg 口服,其余二线以上患者给予每日50 mg 口服,直至疾病进展,观察近期疗效、无进展生存期（PFS）及不良反应。结果全组37例患者,完全缓解（CR）0例,部分缓解（PR）14例（37．8％）,疾病稳定（SD）19例（51．4％）,疾病进展（PD）4例（10．8％）,客观有效率（ORR）37．8％,疾病控制率（DCR）89．2％,PFS 为6．9个月（95％CI 3．8～10．0）。亚组分析显示,一线 EGFR 突变患者ORR 100％,PFS 12．1个月,二线及以上 EGFR 突变未知患者 ORR 14．8％,PFS 5．3个月,两组间差异有显著性意义（P ＜0．01）。最常见的不良反应为腹泻（100．0％）,皮疹（83．8％）。结论阿法替尼用于一线治疗具有 EGFR 基因突变的晚期NSCLC 患者疗效确切,患者耐受性较好。     

临床肿瘤治疗药物相关基因的研究进展

肿瘤化学药物治疗已经在临床上得以广泛应用,但患者对各类治疗药物的敏感性和不良反应存在明显个体差异,药物相关基因指导下的临床肿瘤药物的个体化治疗是肿瘤治疗最重要的发展方向之一。本文主要介绍了5个与临床抗肿瘤药物疗效及毒性相关的基因：二氢嘧啶脱氢酶（DPD）基因突变与5-氟尿嘧啶（5-Fu）的毒性反应;表皮生长因子受体（EGFR）突变与非小细胞肺癌（NSCLC）中吉非替尼、特罗凯的疗效;核苷酸切除修复酶1（ERCC1）基因多态性与铂类化合物疗效;UDP葡萄糖醛酸转移酶1A1（UGT1A1）的遗传变异与羟基喜树碱的毒性反应;胸腺酸合成酶（TS）基因多态性与5-Fu的敏感性,探讨如何预测肿瘤治疗药物的敏感性及不良反应,以指导临床个体化用药。     

Docetaxel in non-small cell lung cancer: impact on quality of life and pharmacoeconomics

Lung cancer is one of the leading causes of cancer-related deaths in industrialised countries, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. A large proportion of patients present with advanced disease and are >65 years of age at the time of diagnosis. Systemic chemotherapy may be offered in an effort to improve survival and quality of life (QOL). Chemotherapy with platinum-based compounds has been shown to modestly improve survival and QOL, and is considered the standard of care as first-line treatment in patients with a good performance status. The last decade has seen the emergence of newer generation chemotherapy agents for the treatment of all cancer types. We review the evidence for the use of docetaxel, an antimicrotubular agent, in patients with advanced NSCLC. In this review, we evaluate not only the effects of docetaxel on survival, but also its impact on QOL and economic issues. Docetaxel is a potent anticancer agent with activity both as a single agent or in combination, and is used both as a first- and second-line treatment in advanced NSCLC. The improvements observed in patients' QOL and the cost effectiveness of docetaxel make it a very reasonable choice in older patients with good performance status and advanced disease who are candidates for chemotherapy.