Adjuvant chemotherapy in non-small cell lung cancer

Lung cancer is the leading cause of cancer death in France. Nearly 80% of lung tumors are non-small cell lung cancers (NSCLC). Surgery is the best curative approach, but it only concerns 30% of NSCLC, since the diagnosis is frequently made in patients with locally advanced or metastatic disease. Even when surgery is performed relapse occurs in up to 50% of patients. Several adjuvant trials have been led in the late 90's after an individual data-based meta-analysis suggested a 5% survival benefit at 5 years. Among those, the IALT study, with 1 867 patients included, confirms the benefit of post-operative chemotherapy in resected NSCLC. In this article, the current status of adjuvant chemotherapy is reviewed, and future prospects are discussed.     

非小细胞肺癌辅助化疗研究进展

近年来,非小细胞肺癌(NSCLC)术后辅助化疗的Ⅲ期随机临床试验结果已陆续报道,术后辅助化疗逐渐被接受,已成为Ⅱ～ⅢA期非小细胞肺癌综合治疗的重要措施之一.本文就NSCLCⅢ期随机临床试验结果作一综述.     

Neoadjuvant chemotherapy in early-stage non-small cell lung cancer

Of the patients that undergo complete resection of early-stage non-small cell lung cancer (NSCLC), 30–60% will die. Postoperative adjuvant chemotherapy has yet to demonstrate an unequivocal benefit and there are significant difficulties in administering postoperative chemotherapy to patients with the significant comorbidities found in NSCLC. Currently, several trials are evaluating the role of preoperative chemotherapy in stage I and II NSCLC. This paper reviews the rationale for this approach and potential future developments.     

Neoadjuvant chemotherapy in early-stage non-small cell lung cancer

Of the patients that undergo complete resection of early-stage non-small cell lung cancer (NSCLC), 30-60% will die. Postoperative adjuvant chemotherapy has yet to demonstrate an unequivocal benefit and there are significant difficulties in administering postoperative chemotherapy to patients with the significant comorbidities found in NSCLC. Currently, several trials are evaluating the role of preoperative chemotherapy in stage I and II NSCLC. This paper reviews the rationale for this approach and potential future developments.     

Adjuvant chemotherapy for non-small cell lung cancer

Nearly half of all patients who undergo surgical resection of localized non-small cell lung cancer (NSCLC) will develop and ultimately die of recurrent disease. The postoperative radiotherapy (PORT) meta-analysis showed adjuvant thoracic radiotherapy to have a detrimental effect on survival in this patient population. A meta-analysis of early trials of adjuvant chemotherapy by the Non-Small Cell Lung Cancer Collaborative Group showed that while chemotherapy with alkylating agents was also detrimental, chemotherapy with cisplatin-based adjuvant chemotherapy was associated with an improved hazard ratio for death (HR = 0.87), equating to a 5 percent survival benefit at 5 years. However, the result was not statistically significant (p = 0.08). Recently, results have been reported for several large Phase III trials of adjuvant chemotherapy which differed with respect to the stage of resected disease included, the type of chemotherapy used and the use of post-operative radiotherapy. Three trials (IALT, JBR 10, and ANITA) that utilized cisplatin-based doublets showed a significantly positive survival benefit of adjuvant chemotherapy in patients with Stage II-IIIA NSCLC. The magnitude of this benefit, which was suggested to be 4-5 percent at 5 years in the meta-analysis and by the IALT study, may be as large as 8-15 percent as indicated by more recent studies with modern platinum-based doublet chemotherapy. These data indicate that medically fit patients with resected Stage II-IIIA NSCLC should be offered adjuvant chemotherapy with a modern cisplatin-based doublet.     

Adjuvant chemotherapy for non-small cell lung cancer

Recently, several randomized trials with a large number of enrolled patients have shown that postoperative adjuvant treatment improves survival among patients with completely resected non-small cell lung cancer (NSCLC). Platinum-based chemotherapy has been reported to be effective for patients with postoperative stage I to IIIA NSCLC in western countries. On the other hand, uracil-tegafur was also shown to improve survival among patients with stage I adenocarcinoma in Japan. We reviewed the results of recent randomized trials and meta-analyses, and discuss the current role and problems related to adjuvant chemotherapy in NSCLC.     

Adjuvant chemotherapy for non-small cell lung cancer

Opinion statement Studies of adjuvant chemotherapy for non-small cell lung cancer (NSCLC) did not provide a consistent disease-free survival or overall survival benefit in the 1980s and early 1990s. However, recently reported studies have changed the practice of NSCLC treatment, for which adjuvant chemotherapy is now considered the standard of care. This review outlines the issues that may have limited the detection of beneficial effects of adjuvant chemotherapy in early trials and provides detailed analysis of the results of recently published trials of adjuvant chemotherapy for NSCLC.     

Adjuvant chemotherapy in resected non-small cell lung cancer

There is still a high mortality ratio in completely resected non-small cell lung cancer patients either due to local or, more often, to metastatic recurrence. The NSCLC Collaborative Group Meta-analysis demonstrated a not statistically significant advantage in patients treated with cisplatin-based regimens. Many subsequent trials were unable to demonstrate the real effectiveness of cisplatin-based adjuvant chemotherapy with a significant rate of toxicity. The IALT trial demonstrated little advantage in overall and disease-free survival with acceptable toxicity. A recent meta-analysis of trials including 5716 patients demonstrated the role of cisplatin-based chemotherapy as adjuvant treatment of resected non-small cell lung cancer even if results shoud be carefully examined. At present, adjuvant chemotherapy in non-small cell cancer should not be reserved to experimental trials.     

Adjuvant chemotherapy and radiotherapy in non-small cell lung cancer

Although surgical resection remains the best potentially curative treatment for non-small cell lung cancer (NSCLC), more than half the patients undergoing resection will eventually die of recurrent disease. Approximately two thirds of relapses occur outside the chest, indicating a potential role for adjuvant chemotherapy. Indeed, a meta-analysis has suggested an absolute survival benefit of 5% at 5 years with adjuvant cisplatin-based regimens. This finding has incited several large-scale randomized trials, the largest of which, the International Adjuvant Lung Trial, has confirmed a similar survival advantage. Conversely, a meta-analysis on postoperative radiotherapy has suggested a detrimental effect, especially for stage I and II patients, that is related most probably to a poor radiation technique. Its value for stage III remains controversial: the observed reduction in local failure did not translate into a survival benefit. In this article, the current status of adjuvant chemotherapy and radiotherapy are reviewed, and future prospects are discussed.     

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer

Introduction: Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years.

Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed.

Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.     

ⅠB期非小细胞肺癌术后辅助化疗的争议和共识

临床上有20％～25％的非小细胞肺癌（NSCLC）患者可手术治疗,但5年生存率也只有40％左右。辅助化疗是部分早期可切除肺癌的标准治疗方式,可使4％～15％的患者生存获益。但是,ⅠB期NSCLC是否能从辅助化疗中获益仍存在争议。近年来,多个临床研究评价了ⅠB期NSCLC辅助化疗的疗效,我们通过分析这些临床研究,寻找ⅠB期NSCLC的高危人群和辅助化疗的适应证。     

Adjuvant immunotherapy for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the biggest cancer killer in the United States and worldwide. In 2011, there are estimated to be 221,130 new cases of lung cancer in the United States. Over a million people will die of lung cancer worldwide this year alone. When possible, surgery to remove the tumor is the best treatment strategy for patients with NSCLC. However, even with adjuvant (postoperative) chemotherapy and radiation, more than 40% of patients will develop recurrences locally or systemically and ultimately succumb to their disease. Thus, there is an urgent need for developing superior approaches to treat patients who undergo surgery for NSCLC to eliminate residual disease that is likely responsible for these recurrences. Our group and others have been interested in using immunotherapy to augment the efficacy of current treatment strategies. Immunotherapy is very effective against minimal disease burden and small deposits of tumor cells that are accessible by the circulating immune cells. Therefore, this strategy may be ideally suited as an adjunct to surgery to seek and destroy microscopic tumor deposits that remain after surgery. This review describes the mechanistic underpinnings of immunotherapy and how it is currently being used to target residual disease and prevent postoperative recurrences after pulmonary resection in NSCLC.     

Adjuvant therapy in resectable non-small cell lung cancer

In order to improve the management of lung cancer at various stages, we analyzed results of treatment in 928 of 1024 patients who were registered at our Hospital Tumor Registry of 1952-1983 with a pathological diagnosis of TNM for carcinoma of the lung after pulmonary resection. The 5-year-survival rate was 43% in 928 patients excluded the cases who were lost follow-up or succumbed within post-operative 1 month. The 5-year-survival rate was 77% for the stage I, 54.7% for the stage II, 17% for the stage III and 4% for the stage IV. The 5-year-survival rate by therapeutic modality was as follows: 52% for the group with chemotherapy, 35% for the one without adjuvant therapies, 29% for the one with irradiation and 15% for the one with radiochemotherapy. Patients with adenocarcinoma who underwent curative surgery showed improvement of survival by postoperative chemotherapy. No increase in survival time was noticed in the irradiated group with N2.     

Multimodality approach to early-stage non-small cell lung cancer

The results of large randomised studies have clearly demonstrated that adjuvant chemotherapy prolongs overall survival by approximately 5% at 5 years in patients with early-stage non-small cell lung cancer (NSCLC). The benefit appears to be largely confined to patients with stage II/III disease, although approximately 25% of patients with stage I disease are at high risk of relapse within 5 years of surgery and therefore could benefit from adjuvant chemotherapy. There is an urgent need to predict more accurately which patients are likely to relapse after surgery and who, therefore, might benefit from further therapy. Preliminary studies indicate that molecular tumour markers may be able to identify tumours that are more likely to respond to chemotherapy and patients who are more likely to achieve improved survival from those who do not benefit at all from adjuvant chemotherapy. A pivotal study has shown that analysis of tumour gene expression can be used to predict the risk of relapse with greater accuracy than that which is achievable using clinical factors. In the future, pharmacogenomics may be used in this approach to identify patients for adjuvant chemotherapy, thus increasing the efficacy of treatment and reducing the burden of therapy in patients who are unlikely to benefit from further therapy.     

Adjuvant chemotherapy for early-stage breast cancer

Systemic chemotherapy is an integral component of the adjuvant treatment strategy for women who have early-stage breast cancer and accounts for significant improvements in breast cancer-specific mortality. Decisions regarding adjuvant therapy are increasingly complex with the advent of new therapeutic strategies, a growing body of literature on the molecular biology and natural history of breast cancer, and advances in therapeutic techniques and early detection. Ultimately, the risk-benefit calculus will continue to evolve in response to these advances and one hopes that clinicians will soon be able to tailor treatment recommendations to the biology of an individual cancer and the needs of the affected individual.     

Adjuvant chemotherapy for non-small cell lung cancer: the new standard of care

Despite optimal surgical therapy for non-small cell lung cancer, approximately 50% of people ultimately die from recurrent disease. Clinical trials in the 1990s suggested a marginal survival advantage associated with adjuvant chemotherapy; however, as the benefit was relatively small and the chemotherapies were not well tolerated, adjuvant chemotherapy was not widely accepted. Over the past 3 years, several large randomized Phase III trials using modern platinum-based doublet regimens in selected patient populations have demonstrated significant survival advantages associated with adjuvant chemotherapy. The recent publication of the JBR10 study clearly exemplifies why this approach is now considered the standard of care for patients with operable non-small cell lung cancer.     

非小细胞肺癌的术后辅助治疗

最近的研究肯定了非小细胞肺癌术后辅助化疗的价值 ,但如何实践应用仍存在不同的看法。通过分析近年几个重要的术后辅助化疗研究 ,形成了中国抗癌协会肺癌专业委员会关于肺癌辅助治疗的共识。