Management of locally advanced NSCLC in the elderly
- Date : 29 Aug 2012
- Topic : Lung and other thoracic tumours
Treatment of locally advanced non-small cell lung cancer (NSCLC) in elderly patients is challenging. The latest phase III clinical trial in this setting, conducted by Japan Clinical Oncology Group, has compared radiotherapy alone with concurrent chemoradiation. The results, published in the July issue of Lancet Oncology, suggest a survival improvement for the combination treatment in selected group of patients. Dr Cesare Gridelli of the Division of Medical Oncology, S. G. Moscati Hospital in Avellino, Italy discuss in the August issue of Nature Reviews Clinical Oncology why the results of that study do not define a new standard of treatment in the entire elderly population.
Compared with their younger counterparts, elderly patients are at higher risk of toxicity owing to reduced organ functions and frequent multiple comorbidities. Lung cancer is more frequent in older patients, with a median age at diagnosis slightly above 70 years, and the main challenge is whether elderly patients can receive the same treatments and derive the same benefit as their younger counterparts.
Early publication of results
Until now, no prospective phase III randomised clinical study that compared concurrent chemoradiation with radiation alone in elderly patients with locally advanced NSCLC has been published whereas several retrospective studies have been reported. The data from these retrospective reports are inconsistent. They included a low number of patients with associated risk of uncontrolled bias. Some analyses showed an excess of toxicity and a lack of survival benefit in the elderly subgroup, other confirmed both the feasibility and efficacy of combined modality treatment in this population, including the more toxicity by concurrent schedule, and further data have demonstrated increased toxicity but survival rates equivalent to those in younger individuals.
Atagi and colleagues had previously reported results from another phase III randomised study in elderly patients (defined as individuals over 70 years) who were randomly assigned to receive either radiation alone or radiotherapy and concurrent daily carboplatin. The results of that study were published in the Japanese Journal of Clinical Oncology. The study was stopped early because four deaths caused by treatment toxicity were observed in the 46 enrolled patients. A specific committee found that only 40% of the patients had radiotherapy fields judged to be protocol compliant in terms of tumour coverage or normal lung restrictions, and half of the treatment-related deaths were judged to be associated with protocol violations.
In their latest study, Atagi and collaborators from the Japan Clinical Oncology Group enrolled 200 elderly patients (over 70 years) with unresectable stage III NSCLC, who were considered as non-eligible for platinum-based doublets due to comorbidity, an ECOG performance status of 2, or age over 74 years. Patients were randomly assigned to receive radiotherapy alone or radiotherapy in combination with carboplatin administered daily at a low dose. The primary end point was overall survival.
The second planned interim analysis was carried out 10 months after completion of patient accrual, and the study data monitoring committee recommended early publication of the results. Median overall survival for the chemoradiation and radiotherapy groups were 22.4 months and 16.9 months, respectively (p = 0.0179). Haematological toxicity was higher in the combination arm compared with the radiotherapy alone in terms of grade 3–4 neutropenia and thrombocytopenia, and was also associated with more grade 3 infection. Pneumonitis, oesophagitis and late lung toxic effects were similar between the two groups.
Can a single study including a limited number of patients define a new standard of treatment?
In his article, Dr Gridelli commented that the results from this study can not be extended to the entire elderly patient population because it included patients with an ECOG performance status of 2 and patients unsuitable for platinum-based doublet chemotherapy. The combination of radiotherapy and daily carboplatin used in this trial is not considered a standard concurrent treatment for locally advanced NSCLC and the study enrolled a low number of patients to give a reliable conclusions. The reported higher toxicity of the concurrent arm and the severe toxicity reported in the previous phase III study by same group should prompt caution.
Dr Gridelli stated that a single study including a limited number of patients can not define a new standard of treatment in a particular subgroup of patients with poor prognosis and at high risk of toxicity. He underlined that patients should be selected not according to chronological age but according to biological age. In Atagi study, the authors considered all patients over 74 years unsuitable for platinum-based regimens regardless of performance status, organ function and presence or absence of comorbidities.
There are no validated and easy-to-use geriatric tools to select patients for chemotherapy, or even specifically for combined chemoradiation. He concluded that prospective phase III elderly-specific trials evaluating the role of combined and particularly concurrent chemoradiation are warranted. According to Dr Gridelli, concurrent approach should be used in clinical practice with caution and reserved only for selected fit patients. The full article with Dr Gridelli view you can read through the ESMO scientific journals access programme.
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