ABSTRACT
BACKGROUND: Nimotuzumab, a humanized monoclonal antibody anti-epidermal growth factor receptor, has been shown to improve survival and quality of life in patients with pediatric malignant brain tumor. It is necessary, however, to increase the objective response criteria to define the optimal therapeutic schedule. The aim of this study was to obtain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) quantitative information related to dimensions and morphology, molecular mobility and metabolic activity of the lesion and surroundings in order to evaluate any changes through time. METHODS: Fourteen pediatric patients treated with nimotuzumab were evaluated on MRI and MRS for >2 years. Each patient was their own control. The MRI/MRS pulse sequence parameters were standardized to ensure experimental reproducibility. RESULTS: A total of 71.4% of patients had stable disease; 21.4% had objective response and 7.1% had progression of disease during the >2 year evaluation period. CONCLUSIONS: MRI/MRS data with clinical information provide a clearer picture of treatment response and confirm once again that nimotuzumab is effective in the treatment of pediatric brain tumor. These imaging procedures can be a useful tool for the clinical evaluation of study protocol in clinical practice.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Brain Neoplasms/drug therapy , Brain/pathology , Magnetic Resonance Imaging/methods , Adolescent , Brain Neoplasms/diagnosis , Child , Child, Preschool , Disease Progression , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Male , Reproducibility of Results , Treatment OutcomeABSTRACT
Epidermal Growth Factor (EGF) promotes tumor cell proliferation and survival upon binding to its receptor. We have developed a new active specific immunotherapy based on EGF deprivation. In the present paper, we show the results of a Phase I trial in 43 patients with advanced non-small cell lung cancer (NSCLC) who received the EGF vaccine. Patients who had already received first line therapy were randomized to receive a single or double dose of the EGF vaccine, weekly for four weeks and monthly thereafter. No significant toxicity was seen after vaccination. Adverse events consisted primarily of fever, chills, nausea, vomiting and flushing. Fifteen patients (39%) developed a good antibody response (GAR) against EGF. The geometric mean of the antibody titer was higher in the double dose group. EGF concentration was quantified in serum. An inverse correlation between anti-EGF antibody titers and EGF concentration was seen after immunization. Vaccinated patients achieved median survival times of 8.23 months from randomization. Patients who received the double dose of treatment showed a trend toward increased survival in comparison with patients who received the single dose. GAR and patients in whom the serum EGF decreased below the 168 pg/ml cut-off point had a significantly better survival when compared to poor responders or patients in which the EGF levels were not considerably reduced. Our results confirm the immunogenicity of the EGF vaccine in the treatment of patients with advanced stage NSCLC. Antibody titers and serum EGF levels appear to correlate with patient survival.
