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Adjuvant chemotherapy for resected non-small-cell lung cancer: future perspectives for clinical research.

ABSTRACT: Adjuvant chemotherapy for non-small-cell lung carcinoma (NSCLC) is a debated issue in clinical oncology. Although it is considered a standard for resected stage II-IIIA patients according to the available guidelines, many questions are still open. Among them, it should be acknowledged that the treatment for stage IB disease has shown so far a limited (if sizable) efficacy, the role of modern radiotherapies requires to be evaluated in large prospective randomized trials and the relative impact of age and comorbidities should be weighted to assess the reliability of the trials' evidences in the context of the everyday-practice. In addition, a conclusive evidence of the best partner for cisplatin is currently awaited as well as a deeper investigation of the fading effect of chemotherapy over time. The limited survival benefit since first studies were published and the lack of reliable prognostic and predictive factors beyond pathological stage, strongly call for the identification of bio-molecular markers and classifiers to identify which patients should be treated and which drugs should be used. Given the disappointing results of targeted therapy in this setting have obscured the initial promising perspectives, a biomarker-selection approach may represent the basis of future trials exploring adjuvant treatment for resected NSCLC.

SUBMITTER: Bonomi M

PROVIDER: S-EPMC3284429 | biostudies-other | 2011 Dec

REPOSITORIES: biostudies-other

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Adjuvant chemotherapy for resected non-small-cell lung cancer: future perspectives for clinical research.

Bonomi Maria M Pilotto Sara S Milella Michele M Massari Francesco F Cingarlini Sara S Brunelli Matteo M Chilosi Marco M Tortora Giampaolo G Bria Emilio E

Journal of experimental & clinical cancer research : CR 20111229

Adjuvant chemotherapy for non-small-cell lung carcinoma (NSCLC) is a debated issue in clinical oncology. Although it is considered a standard for resected stage II-IIIA patients according to the available guidelines, many questions are still open. Among them, it should be acknowledged that the treatment for stage IB disease has shown so far a limited (if sizable) efficacy, the role of modern radiotherapies requires to be evaluated in large prospective randomized trials and the relative impact of ...[more]

PMID: 22206620

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Project description:Most long-term survivors of non-small-cell lung cancer (NSCLC) are patients who have had a completely resected tumour. However, this is only achievable in about 30% of the patients. Even in this highly selected group of patients, there is still a high risk of both local and distant failure. Adjuvant treatments such as chemotherapy (CT) and radiotherapy (RT) have therefore been evaluated in order to improve their outcome. In patients with stage II and III, administration of adjuvant platinum-based chemotherapy is now considered the standard of care, based on level 1 evidence. The role of postoperative radiation therapy (PORT) remains controversial. In the PORT meta-analysis published in 1998, the conclusions were that if PORT was detrimental to patients with stage I and II completely resected NSCLC, the role of PORT in the treatment of tumours with N2 involvement was unclear and further research was warranted. Thus at present, after complete resection, adjuvant radiotherapy should not be administered in patients with early lung cancer. Recent retrospective and non-randomised studies, as well as subgroup analyses of recent randomised trials evaluating adjuvant chemotherapy, provide evidence of the possible benefit of PORT in patients with mediastinal nodal involvement. The role of PORT needs to be evaluated also for patients with proven N2 disease who undergo neoadjuvant chemotherapy followed by surgery. The risk of local recurrence for N2 patients varies between 20% and 60%. Based on currently available data, PORT should be discussed for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy or after surgery if patients have had preoperative chemotherapy. There is a need for new randomised evidence to reassess PORT using modern three-dimensional conformal radiation technique, with attention to normal organ sparing, particularly lung and heart, to reduce the possible over-added toxicity. Quality assurance of radiotherapy as well as quality of surgery - and most particularly nodal exploration modality - should both be monitored. A new large multi-institutional randomised trial Lung ART evaluating PORT in this patient population is needed and is now under way.

Project description:BackgroundAdjuvant chemotherapy (AC) is recommended since 2004 for patients with a completely resected non-small cell lung cancer (NSCLC). Indeed, several randomized clinical trials have demonstrated an improved survival for patients treated with adjuvant cisplatin-based regimen than surgery alone. In these large clinical trials, patients were well selected and fit to receive AC. As the benefit of AC was estimated at 5.4% of 5-year overall survival (OS), it seems important to evaluate AC use in a less selected population. In particular, elderly patients were underrepresented in large randomized clinical trials. Furthermore, other confounding factors might limit AC efficacy in real-life practice such as the delay of chemotherapy initiation following lung surgery or the number of AC cycles received. Therefore, the aim of this systematic review is to summarize the state of the literature on AC use in current clinical practice.MethodsA systematic assessment of literature articles and reviews on AC use in real-life practice was performed by searching in several relevant database including Medline, Google Scholar and Cochrane Library following PICOS (i.e., Population, Intervention, Comparison, Outcomes, Study design) eligibility criteria and PRISMA guidelines. Among the 1,957 results obtained with the request formulated on these research database, 56 relevant articles on AC use in non-trial setting were selected and included in the results section.ResultsThis systematic literature review highlights the lack of literature on AC use in real-life practice as most of these studies were retrospective. Interestingly, a delayed AC-mostly due to postoperative complications-was better than surgery alone. Furthermore, AC was less purposed to elderly patients, despite retrospective studies outlined that this therapeutic option could be benefit in this specific population as for younger patients. In real-life practice, AC was also often incomplete due to adverse events, but dose reduction or omission was not always associated with an inferior survival. In non-trial setting, number of AC cycles delivered, dose reduction or omission is quite similar to randomized clinical trials.DiscussionNowadays, AC is part of the therapeutic strategy used in completely resected NSCLC. In a population of less selected patients, this systematic literature review shows that AC can be used safely and efficiently, especially in elderly patients. As well, delayed AC seems effective. Finally, the place of immunotherapy and targeted therapies have to be precised in the future as well as biomarkers to better select patients that would response to chemotherapy.

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Adjuvant chemotherapy for resected non-small-cell lung cancer: future perspectives for clinical research.

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Adjuvant chemotherapy for resected non-small-cell lung cancer: future perspectives for clinical research.

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