Ben E.E.M. van den Borne

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of osteoporosis. However, the prevalence, correlates and effectiveness of treatment of osteoporosis in COPD patients remain unclear. We performed a systematic review of the literature to answer three questions. 1) What is the prevalence of osteoporosis in COPD? 2) What are identified correlates of osteoporosis in COPD? 3) What are the effects of treatment of osteoporosis in COPD? A computerised literature search in MEDLINE/PubMed and the Cochrane database was carried out. In addition, reference lists were searched by hand and authors were contacted if necessary. The prevalence of osteoporosis and osteopenia varied 9-69% and 27-67%, respectively. Prevalence of osteoporosis was generally higher than in healthy subjects and some other chronic lung diseases. Correlates of osteoporosis in COPD are mainly measures of body composition, disease severity and the use of corticosteroids, although causality has not been proven. Effects of treatment of osteoporosis have not been investigated in samples consisting of COPD patients only. Longitudinal follow-up to assess determinants of osteoporosis in COPD and randomised placebo-controlled trials on the effects of treatment of osteoporosis in patients with COPD only are warranted.

PURPOSE: Cyclooxygenase-2 (COX-2) protein expression in patients with non-small-cell lung cancer (NSCLC) may be not only a prognostic marker but also predictive for COX-2 inhibition. We hypothesized that COX-2 expression is associated with shorter survival and that celecoxib, being a potent COX-2 inhibitor, increases tumor response and survival. PATIENTS AND METHODS: A phase III study was performed in patients with stage IIIb/IV NSCLC who had pathologic confirmation, no prior chemotherapy, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Treatment consisted of docetaxel and carboplatin every 3 weeks for five cycles. Patients were randomly assigned to receive celecoxib 400 mg or placebo twice daily. COX-2 expression on tumor cells was detected by immunohistochemistry. Primary end point was overall survival (OS). RESULTS: From July 2003 to December 2007, 561 patients were randomly assigned. Toxicity was mild, and no increase in cardiovascular events was observed. Tumor response was 38% in the celecoxib arm and 30% in the placebo arm (P = .08). Median progression-free survival was 4.5 months (95% CI, 4.0 to 4.8) for the celecoxib arm and 4.0 months (95% CI, 3.6 to 4.9) for the placebo arm (hazard ratio [HR], 0.8; 95% CI, 0.6 to 1.1; P = .25). Median OS was 8.2 months (95% CI, 7.5 to 8.8) for both treatment arms (HR, 0.9; 95% CI, 0.6 to 1.2; P = .32). COX-2 expression did not independently predict survival. Benefit from celecoxib, restricted to patients with low COX-2 expression, was not significant when adjusted for prognostic factors. CONCLUSION: In advanced NSCLC, celecoxib does not improve survival. In this study, COX-2 expression was not a prognostic biomarker and had no predictive value when celecoxib was added to chemotherapy.