Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. survival was 14.2 months (95% CI 12C16). Conclusion The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, irinotecan and temozolomide for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls. The results from phase III trials are Chondroitin sulfate required before the role of bevacizumab for newly diagnosed glioblastoma is established. INTRODUCTION Glioblastoma is a devastating malignancy, with deleterious consequences on patients quality of life and a poor survival rate. There are approximately 14,000 new cases of glioblastoma diagnosed in the United States annually. (1) The prognosis remains poor, with a median survival of 12C18 months.(2C4) The addition of temozolomide to radiation therapy has improved the survival and has become the standard of care for newly-diagnosed glioblastoma.(4) For patients who underwent a surgical resection, the median survival for patients treated with radiation therapy and daily temozolomide followed by six months of adjuvant temozolomide was 15.8 months.(4) Importantly, the five-year survival was improved with the addition of temozolomide, with 9.8% of patients alive in the combination chemo-radiation therapy group compared 1.9% in the radiation therapy group.(5) Further advances in the survival of patients with glioblastoma must exploit tumor biology. The tumor microenvironment is quite aberrant in glioblastoma, with high interstitial pressure, low pH, and hypoxia, all of which favor tumor development, as well as resistance to chemotherapy and radiation therapy.(6) One of the primary mediators of the tumor microenvironment is vascular endothelial growth factor (VEGF).(7, 8) Glioblastomas have the highest levels of VEGF among malignancies.(9) In addition, VEGF levels appear to be prognostic, with higher levels portending a poor prognosis.(10) Bevacizumab is a humanized monoclonal antibody to VEGF. Bevacizumab is an active treatment for recurrent glioblastoma.(11C13) In a randomized phase 2 trial of bevacizumab or bevacizumab with irinotecan, both groups demonstrated a higher response rate and six month progression-free survival than historical controls.(11) The original recurrent glioblastoma studies that investigated bevacizumab were in combination with irinotecan, so irinotecan was added to the adjuvant bevacizumab and temozolomide in this study to maximize efficacy. Also, the phase II randomized study of bevacizumab or bevacizumab and irinotecan in recurrent glioblastoma patients reported higher response rates and 6 month progression free survivals with the combination.(11) The current trial was designed to incorporate an anti-VEGF therapy into the treatment for newly diagnosed glioblastoma patients. In addition, irinotecan was added Chondroitin sulfate to adjuvant temozolomide with the goal of synergizing a topoisomerase 1 inhibitor with an alkylating agent. METHODS Patients Seventy-five newly diagnosed glioblastoma patients were enrolled in the trial and had received no therapy for their tumor besides surgical resection. Patients had a Karnofsky performance status 60%, and were 18 years of age. Patients enrolled a minimum of two weeks but not six weeks from their last surgical procedure. Eligibility required adequate hematologic and organ function. Patients had uridine glucoronosyl transferase (UGT) Rabbit Polyclonal to ETV6 genotyping. Patients with grade 2 CNS Chondroitin sulfate hemorrhage on their baseline MRI were excluded. All patients gave their informed consent and the protocol was approved by the Duke Institutional Review Board. TREATMENT Surgery The protocol did not mandate the type of surgery however patients who underwent only biopsy were enrolled Chondroitin sulfate in a separate trial for unresectable patients. Patients were evaluated following craniotomy and were required to have fully recovered from their last surgical procedure. Radiation Therapy Patients received radiation therapy according to standard Radiation Therapy Oncology Group guidelines.