• The influence of sex and histology on outcomes in non-small-cell lung cancer: a pooled analysis of five randomized trials.

      Wheatley-Price, P; Blackhall, Fiona H; Lee, Siow Ming; Ma, C; Ashcroft, Linda; Jitlal, M; Qian, W; Hackshaw, A; Rudd, R; Booton, Richard; et al. (2010-03-23)
      BACKGROUND: Some non-small-cell lung cancer (NSCLC) surgical series have indicated that the positive prognostic effect of female sex is limited to patients with adenocarcinoma. We carried out a retrospective analysis to investigate the role of sex and histology on efficacy, toxicity, and dose delivery after chemotherapy. Patient and methods: Individual patient data were pooled from five randomized, phase III, advanced NSCLC chemotherapy trials. Primary outcomes were response rate, overall survival (OS), toxicity, and dose delivery. A secondary analysis examined survival by sex in histological subgroups. RESULTS: Of 2349 patients, 34% were women. Women had a higher response rate to chemotherapy (42% versus 40%, P = 0.01) and longer survival than men (median OS 9.6 versus 8.6 months, P = 0.002). The difference in OS remained after adjusting for age, stage, performance status, and histology (hazard ratio 0.83, 95% confidence interval 0.74-0.92, P = 0.0005). Upon further examination, longer survival in women was only seen in patients with adenocarcinoma (test for interaction P = 0.006). There were no differences in hematological toxicity or transfusions. Women experienced more grade 3-4 emesis than men (P < 0.0001) and more dose delays (P = 0.02) or dose reductions (P < 0.0001). CONCLUSION: The positive prognostic effect among women is confirmed in patients receiving platinum-based chemotherapy but appears confined to those with adenocarcinoma histology.
    • The strength of female sex as a prognostic factor in small-cell lung cancer: a pooled analysis of chemotherapy trials from the Manchester Lung Group and Medical Research Council Clinical Trials Unit.

      Wheatley-Price, P; Ma, C; Ashcroft, Linda; Nankivell, M; Stephens, R J; White, Shane C; Lorigan, Paul C; Thatcher, Nick; Blackhall, Fiona H; Shepherd, F A; et al. (2010-02)
      BACKGROUND: Previous studies reported that women survive longer than men, but experience greater toxicity, when treated for small-cell lung cancer (SCLC). METHODS: Individual patient data from six randomized phase II/III chemotherapy trials, from the Manchester Lung Group and UK Medical Research Council, were pooled for analysis. End points included overall survival, response rate, toxicity, dose intensity (DI) and transfusion rates. RESULTS: Of 1707 patients analyzed, 44% were women. At baseline, women had poorer performance status (PS) (57% versus 67% Eastern Cooperative Oncology Group PS 0-1/Karnofsky PS 80-100, P = 0.0004) and more were of normal weight or underweight (57% versus 48%, P = 0.003), but fewer were anemic (25% versus 62%, P < 0.0001). Response rates between women and men were similar (77% versus 76%, P = 0.64). In univariate [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.76-0.96, P = 0.006] and multivariate (HR 0.88, 95% CI 0.79-0.99, P = 0.04) analyses, female sex predicted for longer survival. Women experienced more grade 3/4 emesis (18% versus 9%, P < 0.0001) and grade 3/4 mucositis (13% versus 8%, P = 0.005) than men. There were no differences in DI, infections, transfusions or treatment-related deaths. CONCLUSION: Data from >1700 patients in randomized SCLC chemotherapy trials confirm that women survive modestly longer than men but may experience greater toxicity.