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• W2003166463 abstract "Adjuvant use of chemotherapy has established efficacy in several solid human tumours – breast, colon and lung cancers being among the most frequent. The role of adjuvant treatment – either locoregionally or systemically after local treatment, allowing a complete resection of the primary tumour and locoregional lymph nodes – is to improve cure rates. The goal of adjuvant chemotherapy is to eradicate micro-metastases that may already be established but are undetectable as well as to destroy possible circulating tumour cells. The benefit, however, is hypothetical, and patients are generally selected on the basis of the pTNM staging obtained at surgery. One has to keep in mind that most of the patients who will be disease-free at 5 years have already been cured by surgery. The benefit of adjuvant chemotherapy is always limited in terms of magnitude to low percentages, and the risk/benefit ratio for a given patient is low. In addition, adjuvant chemotherapy has its own toxicity that may be acute but also long-lasting even after termination. Taking these considerations into account, the use of chemotherapy and the choice of cytotoxic agents should be based on properly conducted clinical trials, with a well-defined population and a follow-up long enough to assure a real benefit with time. Data from efficacy in metastatic settings should not simply be applied to adjuvant use without results of randomised trials in this situation and a proven level of evidence. Tumour cell biology shows that a given tumour evolves with time, and that metastatic disease is quite a different disease from the adjuvant setting.The purpose of this Educational Lecture is:• To review the data on adjuvant chemotherapy for NSCLC.• To analyse how the concept has evolved with time.• To present the results of meta-analysis.• To provide an update on the most recent trials.• To examine the impact on special populations.• To look at possible prognostic/predictive biomarkers.• To provide recommendations for routine practice.2. The first signal of a possible effect of adjuvant chemotherapy in resected NSCLCDuring the last 4 decades of the 20th century, numerous trials of various sample sizes and chemotherapy combinations have been performed in various settings worldwide. Despite an effort to accrue about 10,000 patients in 50 clinical trials, none of them individually has been convincing enough to establish adjuvant chemotherapy as a standard of care. In 1995, the Non-Small Cell Lung Cancer Collaborative Group under the joint auspices of the Medical Research Council (MRC) in the United Kingdom, Institut Gustave Roussy in France and Istituto Mario Negri in Italy published a meta-analysis looking at the impact of adjuvant chemotherapy in resected non-small-cell lung cancer (NSCLC) [1]. They reviewed updated data on individual patients from randomised trials performed between 1965 and 1991. All types of treatment were analysed, including adjuvant chemotherapy, radiation therapy and advanced disease. Among these trials, 14 – including a total of 4357 patients – were performed in the postoperative setting and compared surgery to surgery + chemotherapy. The drugs used were heterogeneous, as were the doses, and overall no benefit on overall survival was shown. The analysis was refined on the basis of the heterogeneity between categories of regimen used, and that was statistically significant. Therefore, chemotherapy regimens were grouped into three categories: (1) long-term alkylating agents, (2) other drugs, and (3) cisplatin-based. No heterogeneity was found within each category, and a separate meta-analysis was performed for each of the three groups. The hazard ratios (HRs) of death showed differences among the groups, already suggesting that the choice of chemotherapy was important: (1) long-term alkylating agents: HR 1.15 (1.04–2.20), P 0.005; (2) other drugs: HR 0.89 (0.72–1.11) P 0.30; and (3) cisplatin-based: HR 0.87 (0.74–1.02) P 0.08.These initial results showed a highly significant detrimental effect of long-term alkylating agents, with a 15% increase in the risk of death from alkylating agents. On the contrary, in the cisplatin-containing regimen group, the benefit, although not significant, showed a 13% reduction in the risk of death, translating into an improved 5% survival at 5 years; however, this survival benefit was not significant, and in practice cisplatin-based adjuvant chemotherapy is not a standard of care for resected NSCLC at this time.Based on the results of the meta-analysis, further randomised trials were performed taking advantage of the “signal” seen earlier with cisplatin-based chemotherapy." @default.
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• W2003166463 date "2013-09-01" @default.
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• W2003166463 title "Adjuvant chemotherapy of non-small-cell lung cancer" @default.
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