Background: Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC. Methods: Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m² of body surface area), gemcitabine (1200 mg/m²), or vinorelbine (25 mg/m²) plus gemcitabine (1000 mg/m²). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles. The primary endpoint was survival. Survival curves were drawn using the Kaplan–Meier method and analyzed by the Mantel–Haenszel test. Secondary endpoints were quality of life and toxicity. Results: Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval [CI] = 0.95 to 1.44) that of patients receiving vinorelbine and 1.06 (95% CI = 0.86 to 1.29) that of patients receiving gemcitabine. Although quality of life was similar across the three treatment arms, the combination treatment was more toxic than the two drugs given singly. Conclusion: The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.

Purpose: Erlotinib prolonged survival of unselected patients with advanced non–small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence. Patients and Methods: Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned. Results: At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation. Conclusion: In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.

Purpose: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non–small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient’s quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. Patients and Methods: Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. Results: Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. Conclusion: Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.

The best treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) is still debated. To guide clinical management of these patients and suggest the priorities for clinical research in this field, an International Expert Panel met in Naples, Italy, on April 19 to 20, 2004. Results and conclusions based on a review of evidence available in the literature to date are presented in this article. A comprehensive geriatric assessment is recommended to better define prognosis and to predict tolerance to treatment. In the first randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine showed superiority over supportive care alone, both in terms of survival and quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed to show any advantage over either agent alone. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. These data should be interpreted cautiously because retrospective subgroup analyses are encumbered by selection bias; hence, randomized trials dedicated to platinum-based chemotherapy for nonselected elderly patients are warranted. Several promising biologic therapies are under investigation; however, with present data, target-based agents as first-line treatment for elderly NSCLC patients are not yet recommended. Clinical research, with trials specifically designed for elderly patients, is mandatory. With the current evidence, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, a taxane) should be the recommended option for nonselected elderly patients with advanced NSCLC. Platinum-based chemotherapy is a viable option for fit patients with adequate organ function. Best supportive care remains important, in addition to chemotherapy or as the exclusive option for patients who are unsuitable for more aggressive treatment.

Docetaxel (75 mg m⁻² 3-weekly) is standard second-line treatment in advanced non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a weekly schedule (33.3 mg m⁻² for 6 weeks) improved quality of life (QoL), a phase III study was performed with 220 advanced NSCLC patients, 75 years, ECOG PS 2. QoL was assessed by EORTC questionnaires and the Daily Diary Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough and hair loss significantly favoured the weekly schedule, while diarrhoea was worse. DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week, while nausea and loss of appetite were more severe in the weekly arm in the third week. Response rate and survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI 0.77–1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia, febrile neutropenia and hair loss; any grade 3–4 haematologic toxicity was significantly more frequent in the standard arm (25 vs 6%). The weekly schedule could be preferred for patients candidate to receive docetaxel as second-line treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and no evidence of strikingly different effect on survival.