ABSTRACT
BACKGROUND: To explore the role of bevacizumab and a chemotherapy-free approach, the authors evaluated the combination of bevacizumab, trastuzumab, and paclitaxel (HAT) and the regimen of trastuzumab and bevacizumab (HA) with the addition of paclitaxel after progression (HA-HAT) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. METHODS: In a noncomparative phase 2 trial, patients were randomized between HAT and HA-HAT. The primary endpoint was the progression-free rate at 1 year (1-year PFR). In the HA-HAT group, progression-free survival (PFS) was separately established for HA (PFS1) and HAT (PFS2). RESULTS: Eighty-four patients received HAT (n = 39) or HA-HAT (n = 45). The 1-year PFR was 74.4% (95% confidence interval [CI], 61.8%-89.4%) and 62.2% (95% CI, 49.6%-89.4%) in the HAT and HA-HAT arms, respectively. The median PFS was 19.8 months (95% CI, 14.9-25.6 months) in the HAT arm and 19.6 months (95% CI, 12.0-32.0 months) in the HA-HAT arm. In the HA-HAT arm, the median PFS1 was 10.4 months (95% CI, 6.2-15.0 months), and the median PFS2 was 8.2 months (95% CI, 7.0-12.6 months). The number and severity of adverse events were comparable between the arms. CONCLUSIONS: Both HAT and HA-HAT have promising activity in patients with HER2-positive metastatic breast cancer. In particular, starting with only targeted agents and delaying chemotherapy is worth further exploration. Cancer 2016;122:2961-2970. © 2016 American Cancer Society.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Breast Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Adult , Aged , Aged, 80 and over , Bevacizumab/administration & dosage , Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Lung Neoplasms/metabolism , Lung Neoplasms/secondary , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Paclitaxel/administration & dosage , Prognosis , Survival Rate , Trastuzumab/administration & dosageABSTRACT
BACKGROUND: Changes in concentration of seminal plasma alpha(1)-acid glycoprotein (AGP) have been studied in detail before. However, the source of high levels of AGP as well as the glycosylation of seminal plasma AGP has not been elucidated yet. METHODS: The glycosylation of AGP was studied by crossed affinity immunoelectrophoresis using fucose-specific lectins and immunostaining. Glycan structure and monosaccharide analyses were performed by high pH anion exchange chromatography with pulsed amperometric detection. Fucosyltransferases were analyzed for activity and their substrate specificity was determined. RESULTS: Two types of fucosylation were detected; Lewis(x) and Lewis(a). Lewis(a) groups were only present on AGP of individuals with a high concentration and were completely absent when the AGP concentration in seminal plasma was low. Lewis(a) expression coincides with a higher degree of branching of the glycans and a relative increased alpha4-fucosyltransferase activity. The molecular weight of all seminal plasma AGP was slightly higher than of blood plasma AGP (approx. 47 vs. 41-43 kDa). CONCLUSIONS: The results indicate that AGP in seminal fluid most likely originates from the prostate and that it is either alpha3- or alpha4-fucosylated.
