Long term responses with cetuximab therapy in glioblastoma multiforme

Abstract

Glioblastoma multiforme (GBM) is responsible for most of the deaths associated with primary brain tumors. Standard treatment includes maximal surgical resection followed by chemotherapy and concomitant radiotherapy. Most patients, however, recur shortly after treatment. Second line treatment has little efficacy and the majority of patients die soon from the disease. Recent advances in molecular biology have implicated the epidermal growth factor receptor (EGFR) signaling pathways in the progression and resistance to standard therapies for GBM. This has prompted the evaluation of EGFR tyrosine- kinase inhibitors with encouraging results. Cetuximab is a monoclonal antibody targeted against the extra cellular domain of the EGFR with activity against different tumor types, either alone or in combination with chemotherapy and/or radiation therapy. Here we describe three patients with recurrent, heavily pretreated, EGFR expressing GBM who responded to treatment with single agent cetuximab.

Radiographic and Histopathologic Observations After Combined EGFR Inhibition and Hypofractionated Stereotactic Radiosurgery in Patients With Recurrent Malignant Gliomas

“…However, reports have previously been published on the radiographic response of gliomas to either molecular targeted agents alone or in combination with chemotherapy (12)(13)(14). In contrast to our present data, these reports focused on the improvement (i.e., decrease in MRI abnormalities) achieved in certain patients with these agents alone.…”

Evolution of Malignant Glioma Treatment

“…Gefitinib, erlotinib, and lapatinib are the best-studied EGFR small molecule inhibitors in clinical trials. Additionally, Cetuximab is a chimeric monoclonal antibody against EGFR that recently was studied in a Phase II clinical trial 38 . Unfortunately, these drugs have only shown modest efficacy for treating malignant glioma.…”

Therapeutic Application of Noncytotoxic Molecular Targeted Therapy in Gliomas: Growth Factor Receptors and Angiogenesis Inhibitors

“…Indeed, no clinical trial has been published. Anecdotally, Belda- Iniesta et al [47] described three patients with recurrent EGFR-expressing glioblastomas who responded to cetuximab as a single therapeutic agent. The tolerance was acceptable with moderate asthenia and skin rash.…”