Subjects >= 18 yr of age with serum alpha1-antitrypsin (alpha1-AT) levels <= 11 microM or a ZZ genotype were followed for 3.5 to 7 yr with spirometry measurements every 6 to 12 mo as part of a National Heart, Lung, and Blood Institute Registry of Patients with Severe Deficiency of Alpha-1-Antitrypsin. Among all 1,129 enrollees, 5-yr mortality was 19% (95% CI: 16 to 21%). In multivariate analyses of 1, 048 subjects who had been contacted >= 6 mo after enrolling, age and baseline FEV1% predicted were significant predictors of mortality. Results also showed that those subjects receiving augmentation therapy had decreased mortality (risk ratio [RR] = 0.64, 95% CI: 0. 43 to 0.94, p = 0.02) as compared with those not receiving therapy. Among 927 subjects with two or more FEV1 measurements >= 1 yr apart, the mean FEV1 decline was 54 ml/yr, with more rapid decline in males, those aged 30 to 44 yr, current smokers, those with FEV1 35 to 79% predicted, and those who ever had a bronchodilator response. Among all subjects, FEV1 decline was not different between augmentation-therapy groups (p = 0.40). However, among subjects with a mean FEV1 35 to 49% predicted, FEV1 decline was significantly slower for subjects receiving than for those not receiving augmentation therapy (mean difference = 27 ml/yr, 95% CI: 3 to 51 ml/yr; p = 0.03). Because this was not a randomized trial, we cannot exclude the possibility that these differences may have been due to other factors for which we could not control.

Denosumab offers an alternative, or additional, treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumours

BACKGROUND:A retrospective evaluation of single agent bevacizumab was carried out in adults with recurrent alkylator‐refractory 1p19q codeleted anaplastic oligodendrogliomas (AO) with an objective of determining progression‐free survival (PFS). There is no standard therapy for alkylator‐resistant AO, and hence a need exists for new therapies.METHODS:Twenty‐two patients aged 24 to 60 years with recurrent AO were treated. All patients had previously been treated with surgery, radiotherapy, adjuvant chemotherapy (temozolomide, 17; carmustine wafers, 4; carmustine, 1), and 1 salvage regimen (procarbazine, lomustine, and vincristine, 15; temozolomide, 6; carmustine wafers, 1). Eleven patients underwent repeat surgery. Patients were treated at second recurrence with bevacizumab, once every 2 weeks, defined as a single cycle. Neurological evaluation was performed every 2 weeks, and neuroradiographic assessment was made after the initial 2 cycles of bevacizumab and subsequently after every 4 cycles of bevacizumab.RESULTS:A total of 391 cycles of bevacizumab (median, 14.5 cycles; range, 2‐39 cycles) were administered. Bevacizumab‐related toxicity included fatigue (14 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (5; 1 grade 3), deep vein thrombosis (4; 1 grade 3), and wound dehiscence (2; 1 grade 3). Fifteen (68%) patients demonstrated a partial radiographic response, 1 (5.0%) demonstrated stable disease, and 6 (27%) demonstrated progressive disease after 2 cycles of bevacizumab. Time to tumor progression ranged from 1 to 18 months (median, 6.75 months). Survival ranged from 3 to 19 months (median, 8.5 months). Six‐month and 12‐month PFS were 68% and 23%, respectively.CONCLUSIONS:Bevacizumab demonstrated efficacy and acceptable toxicity in this cohort of adults with recurrent 1p19q codeleted alkylator‐refractory AO. Cancer 2009. © 2009 American Cancer Society.