ARTICLE ARTICLES ynergism of Epidermal Growth Factor Receptor–Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo

Background: Epithelial ovarian cancer often develops resis-tance to standard treatments, which is a major reason for the high mortality associated with the disease. We examined the effi cacy of a treatment regimen that combines immunothera-py to block the activity of epidermal growth factor receptor (EGFR), overexpression of which is associated with the de-velopment of resistant ovarian cancer, and photodynamic therapy (PDT), a mechanistically distinct photochemistry-based modality that is effective against chemo- and radio-resistant ovarian tumors. Methods: We tested a combination regimen consisting of C225, a monoclonal antibody that inhibits the receptor tyrosine kinase activity of EGFR, and benzoporphyrin derivative monoacid A (BPD)-based PDT in a mouse model of human ovarian cancer. Therapeutic effi cacy was evaluated in acute treatment response and survival studies that used 9 – 19 mice per group. Analysis of variance and Wilcoxon statistics were used to analyze the data. All statistical tests were two-sided. Results: Mice treated with PDT + C225 had the lowest mean tumor burden compared with that in the no-treatment control mice (mean percent tumor burden = 9.8%, 95 % confi dence interval [CI] = 2.3% to 17.3%, P<.001). Mean percent tumor burden for mice treated with C225 only or PDT only was 66.6 % (95 % CI = 58.7 % to 74.4%, P<.001) and 38.2 % (95 % CI = 29.3 % to 47.0%, P<.001), respectively. When compared with PDT only or C225 only, PDT + C225 produced synergistic reductions in mean tumor burden (P<.001, analysis of variance) and im-provements in survival (P =.0269, Wilcoxon test). Median survival was approximately threefold greater for mice in the PDT + C225 group than for mice in the no-treatment control group (80 days versus 28 days), and more mice in the PDT + C225 group were alive at 180 days (3/9; 33 % [95% CI = 7 % to 70%]) than mice in the C225-only (0/12; 0