Phase II study of MEDI-575, an anti-platelet-derived growth factor-α antibody, in patients with recurrent glioblastoma.

MEDI-575, an immunoglobulin G2κ monoclonal antibody, selectively binds to platelet-derived growth factor-α receptor (PDGFR-α) with high specificity. This multicenter, single-arm, open-label, phase II study evaluated the efficacy and safety of MEDI-575 in patients with recurrent glioblastoma. Adults with first recurrence of glioblastoma following surgery, temozolomide, and radiation received MEDI-575 25 mg/kg intravenously over 60 min every 21 days until disease progression or unacceptable toxicity. Six-month progression-free survival rate (PFS-6) was the primary end point; secondary measures included response rate, overall survival (OS), and safety/tolerability. PDGFR-α expression was evaluated by immunohistochemistry. Fifty-six patients were enrolled; median age was 56.5 years (range 23-79), 66 % were male, and 66 % were aged ≥65 years. PFS-6 was 15.4 % [90 % confidence interval (CI) 8.1-24.9]. No complete or partial responses were observed; 23 (41.1 %) patients had stable disease as best response. Median PFS was 1.4 months (90 % CI 1.4, 1.8); median OS was 9.7 months (90 % CI 6.5, 11.8). The most common treatment-related adverse events (AEs) were diarrhea (16 %), nausea (13 %), and fatigue (13 %). Twelve (21 %) patients reported grade ≥3 AEs, with hydrocephalus (n = 3), dysphagia (n = 2), and convulsion (n = 2) reported in more than 1 patient. Two patients had treatment-related Grade ≥3 AEs of decreased lymphocyte count and asthenia (n = 1 each). Seven patients (13 %) discontinued MEDI-575 owing to AEs. Labeling of PDGFRα in glioblastoma cells and tumor-associated stromal cells was highly variable, with no correlation with PFS. MEDI-575, although well tolerated, had limited clinical activity in recurrent glioblastoma.

Most severe neutropenia in individuals with no chronic condition did not result in a specific diagnosis.

BACKGROUND AND OBJECTIVES: This study estimated the incidence of unexplained severe neutropenia (neutrophil count 500 x 10(6)/L) and hospitalized morbidity in the year after a finding of severe neutropenia in persons 2 years of age or older based on clinical laboratory data. METHODS: Computer-stored data from the Kaiser Permanente Laboratory Management System/Results Management System were used to identify findings of severe neutropenia in members of Kaiser Permanente Southern California 2 years of age or older during the period January 1, 1997, through December 31, 1999. Computer record linkage and medical record review were used to exclude individuals with chronic disease or treatments with bone marrow toxic drugs known to cause neutropenia. RESULTS: The incidence of findings of severe neutropenia was 47 per million persons per year (95% CI=42-53). Only 11% of individuals with a finding of severe neutropenia were hospitalized with neutropenia diagnosis. The hospitalization rate for infection occurring within 1 year of severe neutropenia was 3.2% (95% CI=1.5-6.2%). CONCLUSION: Most laboratory findings of severe neutropenia in individuals with no chronic condition do not result in a specific diagnosis. In a population-based sample of findings of severe neutropenia identified by laboratory testing, hospitalization for infection was rare.