E-34. Chemotherapy for non-small cell lung cancer in the elderly

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Introduction: Non small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of lung cancer patients are diagnosed over the age of 65 and about 30% over the age of 70. More than two-thirds of patients dying of lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly because of comorbidity and organ failure. The prevalence of these co-morbid conditions is about twice as high as in the general population. Elderly patients with NSCLC, who frequently suffer tumor-related symptoms and need some kind of palliative treatment, often receive untested or inadequate treatments. A cut-off of 70 years seems to be the most appropriate to select elderly population. In fact, 70 years of age may be considered as the lower boundary of senescence, because the incidence of age-related changes starts to increase after the age of 70 years. Relevant data: In early stages, to date, neither neoadjuvant nor postoperative chemotherapy should be advised in clinical practice outside clinical trials in the elderly. Combined chemoradiotherapy in locally advanced disease, particularly with concurrent approach should be investigated in specific trials before to be preferred in clinical practice to radiation therapy alone. In advanced disease, recently, a retrospective trial of 6232 elderly patients from the SEER tumor registry showed that chemotherapy for metastatic NSCLC seems to have the same effectiveness as that seen in randomized trials with mostly younger patients [I]. Therefore, all suitable patients should be given the opportunity to consider palliative chemotherapy for advanced NSCLC. Prospective phase II trials have demonstrated suitable toxicity profile and good antitumor activity for single agent chemotherapy with the recently developed drugs vinorelbine, gemcitabine and taxanes. Prospective data on weekly paclitaxel have been recently published. Fidias et al, used weekly paclitaxel on 35 advanced NSCLC elderly patients reporting a good tolerability and interesting results with 23% OR and 10.3 months of median survival [2]. Docetaxel has been tested as well in the elderly population. Hainsworth et al reported for weekly docetaxel 18% OR, a median survival of 5 months and a favourable toxicity profile [3]. Gemcitabine is the most widely investigated agent in advanced NSCLC elderly patients, reported as an active, effective and very well tolerated drug in this peculiar patient population, with response rates ranging from 16% to 33% and median survival of 29-32 weeks [4]. In phase II studies, single agent vinorelbine proved to be well-tolerated and active, with response rates of 12%-39% [5]. Vinorelbine, in a phase III randomized trial named ELVIS (Elderly Lung Cancer Vinorelbine Italian Study), compared to best supportive care, has proven to improve survival and quality of life of advanced NSCLC patients [6]. As the ELVIS trial is the unique randomized controlled trial versus best supportive care ever performed in the treatment of elderly patients with advanced NSCLC, its result is the most reliable evidence on the efficacy of chemotherapy in this subgroup of patients. In order to improve results obtained with monochemotherapy, the development of non cisplatin-based combinations is an interesting issue in the treatment of advanced NSCLC elderly patients. In fact the possibility of having active and well-tolerated chemotherapy while preserving patient quality of life is more attractive in the elderly. The most studied non platin-based regimen is the combination of gemcitabine plus vinorelbine, resulted active and well-tolerated in several phase II trials [4]. However, a recent large phase III randomized trial (MILES-Multicenter Italian Lung cancer in the Elderly Study), enrolling about 700 patients, showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome (response rate, time to progression, survival or quality of life) as compared to single agent chemotherapy with vinorelbine or gemcitabine [7]). In clinical practice, single agent chemotherapy should remain the standard treatment. Feasibility of cisplatin-based polychemotherapy remains an open issue and has been recently addressed by three retrospective analyses of randomized trials without age limits, suggesting that advanced age alone should not preclude aggressive cisplatin-based treat-