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: Since treatment efficacy of cisplatin- or carboplatin-based chemotherapy in the first-line treatment of small-cell lung cancer (SCLC) remains contentious, a meta-analysis of individual patient data was performed to compare the two treatments. Patients and Methods: A systematic review identified randomized trials comparing cisplatin with carboplatin in the first-line treatment of SCLC. Individual patient data were obtained from coordinating centers of all eligible trials. The primary end point was overall survival (OS). All statistical analyses were stratified by trial. Secondary end points were progression-free survival (PFS), objective response rate (ORR), and treatment toxicity. OS and PFS curves were compared by using the log-rank test. ORR was compared by using the Mantel-Haenszel test. Results: Four eligible trials with 663 patients (328 assigned to cisplatin and 335 to carboplatin) were included in the analysis. Median OS was 9.6 months for cisplatin and 9.4 months for carboplatin (hazard ratio [HR], 1.08; 95% CI, 0.92 to 1.27; P = .37). There was no evidence of treatment difference between the cisplatin and carboplatin arms according to sex, stage, performance status, or age. Median PFS was 5.5 and 5.3 months for cisplatin and carboplatin, respectively (HR, 1.10; 95% CI, 0.94 to 1.29; P = .25). ORR was 67.1% and 66.0%, respectively (relative risk, 0.98; 95% CI, 0.84 to 1.16; P = .83). Toxicity profile was significantly different for each of the arms: hematologic toxicity was higher with carboplatin, and nonhematologic toxicity was higher with cisplatin. Conclusion: Our meta-analysis of individual patient data suggests no differences in efficacy between cisplatin and carboplatin in the first-line treatment of SCLC, but there are differences in the toxicity profile.

Platinum-based chemotherapy remains the standard-of-care for most patients affected by advanced non-small cell lung cancer (NSCLC). The platinum compounds currently used in NSCLC are cisplatin and carboplatin. The availability of new generation drugs has led to the adoption of schedules with lower doses of platinum compounds leading to increased tolerability. Several data suggest that third generation cisplatin-based regimens are slightly superior to carboplatin-based chemotherapy, with a different safety profile, and so cisplatin should remain the standard reference for the treatment of selected patients with advanced NSCLC. Recent evidence emphasized that the optimal number of first-line platinum cycles should be four for any NSCLC histology. New platinum compounds and the use of functional genomics to deliver platinum drugs as personalised medicine, are being investigated. Here we review the current status of cisplatin and carboplatin regimens looking to the future role of platinum compounds in...

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: To investigate the activity and toxicity of gemcitabine as a single agent in patients with advanced non–small-cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. PATIENTS AND METHODS: From November 1995 to October 1997, 83 patients with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m² once a week for 3 weeks every 28 days. Responses were assessed every two treatment courses. The median age of the patients was 63 years; Eastern Cooperative Oncology Group performance status was 0 to 1 in 62 patients and 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and one stage IIIA). RESULTS: Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well tolerated: grade 2 to 3 (World Health Organization standardized response criteria) leukopenia and thrombocytopenia occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients, and peripheral edema in 5% of patients. Nausea and vomiting were present in 16% of patients. CONCLUSION: In this experience, gemcitabine showed significant activity without relevant toxicity, mainly in patients who were previously responsive to chemotherapy. This suggests a possible role for gemcitabine as a second-line treatment in patients who had a previous response or achieved stable disease with a platinum-containing regimen.

Purpose: Elderly patients often have comorbidities and other characteristics that make the selection of treatment daunting. Methods: We have reviewed the available evidence in the literature to gauge the results of therapy for elderly lung cancer patients. Results: The beneficial results achieved with adjuvant chemotherapy in the general population with early non–small-cell lung cancer (NSCLC) cannot be automatically extrapolated to the elderly, who are at higher risk of toxicity. Retrospective analyses of combined chemoradiotherapy in locally advanced NSCLC patients suggest equivalent therapeutic benefit for younger and older patients, despite heightened toxicity. There have been no elderly-specific phase III trials for locally advanced NSCLC. For advanced NSCLC, on the basis of evidence-based data, single-agent chemotherapy remains the standard of care for nonselected elderly patients. However, retrospective analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with increased but acceptable toxicity for elderly patients. In limited-disease small-cell lung cancer (SCLC), sequential chemoradiotherapy is clearly less toxic compared with a standard concurrent approach, but our assessment of treatment is hindered by the absence of prospective elderly-specific trials. Although prophylactic cranial irradiation has emerged as a standard strategy, it should be omitted in patients with cognitive impairment. In extensive SCLC, etoposide in combination with either cisplatin or carboplatin has emerged as standard treatment; hematopoietic support may be necessary. Conclusion: With the exception of advanced NSCLC, prospective elderly-specific studies are lacking. Available data suggest that outcomes in the fit elderly mirror results observed in younger patients, although toxicity is generally worse.