Elderly patients and younger "unfit" patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) (> or = 2) suffering from advanced
non-small-cell lung cancer (NSCLC) are two different populations--both of which require
palliative treatments. Elderly patients frequently experience progressive decline of organ function and multiple comorbidities, which need to be considered when choosing
therapy. ECOG 1594 showed that advanced NSCLC patients with an ECOG PS of 2 did not tolerate
platinum-based
chemotherapy (
cisplatin/
paclitaxel,
carboplatin/
paclitaxel, cisplatin/
docetaxel,
carboplatin/
paclitaxel). These data confirm that treatments designed specifically for this patient subset are needed. Single-agent
chemotherapy seems to be a reasonable approach, and non-
platinum-based
combination chemotherapy should also be investigated. The oncology community has become increasingly aware of the magnitude of the problem of
cancer in the elderly. More than 30% of
lung cancers arise in patients > or = 70 years old. Elderly patients tolerate
chemotherapy poorly, according to the few published papers, and are not considered eligible for aggressive
cisplatin-based
chemotherapy in clinical practice. A phase III randomized trial (
ELVIS [Elderly
Lung Cancer Vinorelbine Italian Study]) demonstrated survival and quality-of-life benefits with single-agent
vinorelbine versus best supportive care. Among the newer drugs,
gemcitabine has demonstrated activity and low toxicity in phase II studies. With this background, we performed a randomized, multicenter phase III trial (MILES [Multicenter Italian
Lung Cancer in the Elderly Study]) in 707 advanced NSCLC elderly patients. The MILES study compared single-agent
chemotherapy with
vinorelbine or
gemcitabine versus
polychemotherapy with
gemcitabine plus
vinorelbine. Results showed no benefit in response rate, time to progression, survival, and quality of life for the combination. Single-agent
chemotherapy remains the standard treatment approach for elderly NSCLC patients with advanced disease.